PB-195 888
PATHO-PHYSIOLOGIC RESPONSE TO SINGLE AND
MULTIPLE AIR POLLUTANTS IN HUMANS AND
ANIMALS
Morton Corn, et al
Pittsburgh University
Pittsburgh, Pennsylvania
1 July 1970
DISTRIBUTED BY:
National Technical Information Service
U. S. DEPARTMENT OF COMMERCE
5285 Port Royal Road, Springfield Va. 22151
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PB195888
FINAL REPORT
PATHO-PHYSIOLOGIC RESPONSE TO SINGLE AND MULTIPLE
AIR POLLUTANTS IN HUMANS AND ANIMALS
Covering the Period
January 16, 1968 - May 31, 19 70
Contract No. PH 86-67-73
Prepared for
National Air Pollution Control Administration
Consumer Protection and Environmental Health Service
U. S. Public Health Service
By
Morton Corn, Ph.D., Principal Investigator
with the assistance of
Nancy Kotsko, Dolores Stanton, William Bell,
and Armand P. Thomas
Graduate School of Public Health
University of Pittsburgh
July 1, 1970
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NOTICE
THIS DOCUMENT HAS BEEN REPRODUCED FROM THE
BEST COPY FURNISHED US BY THE SPONSORING
AGENCY. ALTHOUGH IT IS RECOGNIZED THAT CER-
TAIN PORTIONS ARE ILLEGIBLE, IT IS BEING RE-
LEASED IN THE INTEREST OF MAKING AVAILABLE
AS MUCH INFORMATION AS POSSIBLE.
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STANDARD TITLE PAGE
FOR TECHNICAL REPORTS
4. Title and Subtitle
1. Report No.
APTD-0593
3. Recipient s Catalog No.
Patho-Physiologic Response to Single and Multiple Air
Pollutants in Humans and Animals
5. Report Oate
July 1. 1970
6, Performing Organization Code
1. Author(s)
Morton Corn, Ph.D.
8. Performing Organization Rept. No.
9. Performing Organization Name and Address
Department of Occupational Health
Graduate School of Public Health
University of Pittsburgh
Pittsburgh, Pennsylvania 15213-.
12. Sponsoring Agency Name and Address
DHQVj PHS, EHS
National Air Pollution Control Administration Technical Center
411-Wast Chapel Hill Street
Durham, North Carolina 27701
15. Supplementary Notes —————
10. Project/Task/Work Unit No.
IT. Contract7Grant NoT
PH 86-67-73
13. Type of Report & Period Covered
14. Sponsoring Agencytode
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16. Abstracts Twenty healthy, adultmale cats were lightly anesthetized (Nembutal), tracheotoalied
d were then breathed by a Harvard putt? at a fixed frequency and tidal volume. Purified Med: ca:
ade breathing air with or without sulfur dioxide in air or sulfur dioxide in combination w: th
(jdium chloride aerosol in1 air, was (SaldVared to the animals in predetermined exposure sequen
and for fixed durations of time.-Parametens of response used to judge adaptation of catslto
e inhaled challenges of pollutants ^e^re .pulmonary flow resistance and lung compliance. Mea
rement methods were standard and,included continuous trace recordings of air flow, tidal v<|l-
tije, transpulmonary pressure and biood^reesure. Each animal acted as his own control. In ad< i-
on, pollutant mixtures werf'e 'deili^et'OTp'tb'atiiinals via endotracheal catheter and/or face masl
evaluate the possible influence of receptors which may be present in the nasopharyngeal cLam-
r and in the trachea above the tracheal'cartmila. After selected exposures, the pleural cav:.ty
s opened and liquid Freon was used to freeze the lungs. Procedures were developed to obtaiii
stological sections in order to measure changes in airway size. The major finding was the
riability of the responses of the test animals. Certain subjects showed increased pulmonar1
ov resistance at low S02 concentration, and were the analogues of the "reactors" in human
pulations. Approximately 20 ppm S02 in air were required to evoke a significant change in
Imnnary fl— ^ ¦* - " —J —J c 1 J - " "' '
Wc
Nose (anatomy)
Pharynx
Size determination
Variability
Concentration (composition)
17. Key Aoids and Document Analysis, (a). Descriptor
Air pollution
Sulfur dioxide
Aerosols
Cats
S odium Chloride
Lung
Air flow
Resista'nce
Elastic properties
Trachea
17b. Idcntlflers/OpeivEnded Terms
Pulmonary flow resistance
Lung compliance
17c. COSATl Field/Group 13/02, 06/06, 06/16, 06/19, 06/20
a/
(over)
18. Distribution Stntement
Un I .Lmi ted
19.Security Cl3ss(This Roport)
UNCLASSIFIED
21. No. of Pages
125
/tl.Sccurity Class.(This Page)
UNCLASSIFIED
22. Price
FORM NBS-867O-70)
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This report was furnished to the National
Air Pollution Control Administration by the
Graduate School of Public Health, Univer-
sity of Pittsburgh in fulfillment of Con-
tract No. PH 86-67-73.
Abstracts (Cont'd)
concentration of sulfur di'6xi<3^r!£9',5fr i either alone or in the presence of NaCl aerosol
(10 mg/m3). When the pollutants were^administered via endotracheal catheter and face mask,
an ^cregsedfrequen^ gf^ianif leant-changes in pulmonary flow resistance in these ani-
mala^r^cexviing cViallengea' oy" tracheal-"cannula. However, fewer test animals were used in
the fofthfctf 'dt^tidi,e4^', All!',*lt£t,Ation8,titf parameters' of response werfe' reversible shortly
after exposure ceased. Morphological ^-examination' of lung tissue sections after rapid
freezing with Freon indicated that'toaaauir'^ment of alterations In airway size is not
possible in the range o£ changes "of "pulmonary flow resistance reported here (c. 100%).
Methods and data for aliL experiments are presented in detail.
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SUMMARY
Twenty healthy, adult male cats were lightly anesthetized
(Nembutal), tracheotomized and were then breathed by a Harvard
pump at a fixed frequency and tidal volume. Purified Medical
Grade breathing air with or without sulfur dioxide in air or
sulfur dioxide in combination with sodium chloride aerosol in
air, was delivered to the animals in predetermined exposure
sequences and for fixed durations of time. Parameters of re-
sponse used to judge adaptation of cats to the inhaled chal-
lenges of pollutahts were pulmonary flow resistance and lung
compliance. Measurement methods were standard and included
continuous trace recordings of air flow, tidal volume, trans-
pulmonary pressure and blood pressure. Each animal acted as
his own control. In addition, pollutant mixtures were delivered
to animals via endotracheal catheter and/or face mask to evalu-
ate the possible influence of receptors which may be present in
the nasopharyngeal chamber and in the trachea above the tracheal
cannula. After selected exposures, the pleural cavity was
opened and liquid Freon was used to free£e the lungs. Pro-
cedures were developed to obtain histological sections in order
to measure changes in airway size.
The major finding of -the study was the variability of the
responses of ,the test animals. Certain subjects showed increased
pulmonary flow resistance at low SO2 concentration, and were the
i
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analogues of the "reactors" in human populations. Approximate-
ly 20 ppm SO2 in air were required to evoke a significant change
in pulmonary flow resistance in ''reactors". The majority of
animals showed no response at this concentration of sulfur di-
oxide in air, either alone or in the presence of NaCl aerosol
3
(10 mg/m ). When the pollutants were administered via endotra-
cheal catheter and face mask, an increased frequency of signifi-
cant changes in pulmonary flow resistance in those animals was
suggested., as compared to animals receiving challenges by tra-
cheal cannula. However, fewer test animals were used in the
former studies.
sAll alterations in parameters of response were reversible
shortly after exposure ceased.s This finding in cats is similar
to reports of early reversal of these parameters in spontaneous-
ly breathing human subjects exposed to the same pollutants. In
guinea pigs, pulmonary flow resistance, which was elevated by
exposure to pollutants, returned to normal after a prolonged
period (at least one hour) following cessation of exposure.
Morphological examination of lung tissue sections after
rapid freezing with Freon indicated that measurement of alter-
ations in airway size is not possible in the range of changes
of pulmonary flow resistance reported here (< 100%).
Methods and data for all experiments are presented in
detail.
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TABLE OF CONTENTS
SUMMARY .
LIST OF FIGURES . . . .
LIST OF TABLES ...
I. INTRODUCTION
II. EXPERIMENTAL METHODS
A. Pollutant Aerosol and Gas Generation . i . . .
B. Pollutant Gas and Aerosol Sampling and Analy-
sis . . .
1. Sulfur Dioxide
2. Sodium Chloride Aerosol . .
C. Animal Handling and Preparation
D. Determination of Pulmonary Flow Resistance and
Lung Compliance
E. Conduct of Experiments . . .
F. Treatment of Data
G. Pathological Procedures
III. RESULTS AND DISCUSSION . . .
A. Changes in Pulmonary Flow Resistance and Lung
Compliance in Cats Following Pollutant Chal-
lenges
B. Changes in Pulmonary Flow Resistance and Lung
Compliance in Guinea Pigs Following Pollutant
Challenges
C. Pathological Changes in Cats Following Pollu-
tant Exposures
REFERENCES
APPENDIX A - Reprint
APPENDIX B - Tabular and Graphical Records of In-
Page
i
iii
iv
1
4
4
6
6
9
11
15
20
22
28
30
30
34
37
42
dividual Experiments.
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analogues of the "reactors" in human populations. Approximate-
ly 20 ppm SC>2 in air were required to evoke a significant chang
in pulmonary flow resistance in "reactors". The majority of
animals showed no response at this concentration of sulfur di-
oxide in air, either alone or in the presence of NaCi' aerosol
3
(10 mg/m ). When the pollutants were administered via endotra-
cheal catheter and face mask, an increased frequency of signifi
cant changes in pulmonary flow resistance in these animals was
suggested, as compared to animals receiving challenges by tra-
cheal cannula. However, fewer test animals were used in the
former studies.
•All alterations in parameters of response were reversible
shortly after exposure ceased. This finding in cats is similar
to reports of early reversal of these parameters in spontaneous
ly breathing human subjects exposed to the same pollutants. In
guinea pigs, pulmonary flow resistance, which was elevated by
exposure to pollutants, returned to normal after a prolonged
period (at least one hour) following cessation of exposure.
Morphological examination of lung tissue sections after
rapid freezing with Freon indicated that measurement of alter-
ations in airway size is not possible in the range of changes
of pulmonary flow resistance reported here (< 100%).
Methods and data for all experiments are presented in
detai1.
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LIST OF FIGURES
1. Schematic of Pollutant Generation Apparatus.
2. Calibration Curve for SC^ Using Modified West-Gaeke Pro-
cedure.
3. Cumulative Particle-rSize Distribution Curve for Test Aero-
sol Sized at 32,000X Magnification.
4. Typical Variations in Pollutant Concentrations During an
Experiment.
5. Representative Sweep and Loop Tracings Using Electronics for
Medicine Rapid Writer and LW-27, 18 cm Photographic Paper.
6. Photograph Showing Cat Artificially Ventilated by Harvard
Pump.
7. Cannula Arrangements for Exposure Via Tracheal Cannula and
for Above and Below Tracheal Cannula.
8. Graphical Summary of Variations in RL and CL During an Ex-
periment.
9. Photomicrograph of a Thick Section of the Right Lung Lobe
of a Male Cat (No. 1112).
10. Photomicrograph of a Thick Section of the Right Lung Lobe
of a Female Cat (No. 1144).
11. Photomicrograph of a Thin Section of the Right Lung Lobe
of a Male Cat (No. 1610).
iii
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LIST OF TABLES
1. Parameters Recorded with the Electronics for Medicine Unit
and Associated Transducers.
2. Response to Various Stimuli Expressed as Percent Change Re-
lative to Control Values.
3. Summary of R^ and CL Responses (P > 0.01) of Cats Exposed
to Pollutant Mixtures in this Study (Tracheal Cannula Pollu-
tant Delivery).
4. Summary of and C^ Responses (P > 0.01) of Cats Exposed to
Pollutant Mixtures in this Study (Endotracheal Catheter Pol-
lutant Delivery).
5. Summary of R^ and CL Responses (P > 0.01) of Cats Exposed
to Pollutant Mixtures in this Study (Double Cannula Pollu-
tant Delivery).
6. Summary of Calculated Results of R_ and CT for Experiments
I.* Lf
with Cat No. 1651.
iv
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I. INTRODUCTION
A. Review of Contract Aims and Efforts
This Contract was initiated on January 3, 1957. Its aim was
to perform a series of experiments in animals and in man to de-
termine the extent of and the mechanisms associated with, syner-
gism between inert aerosols and irritant gas in combination after
inhalation. The parameters used to judge synergistic response
were to be changes in pulmonary mechanics. Initially, it was our
aim to study humans in both the resting state and during exercise.
The departure from this laboratory of Dr. George Burton for Loma
Linda University in 1968 resulted in curtailment of human studies
because a physician was not associated with the study, thus pre-
cluding adherence to University guidelines for experiments in-
volving human subjects. However, studies involving exposures of
human subjects at rest were completed and a publication entitled
"Response of Healthy Men to Inhaled Low Concentrations of Gas-
Aerosol Mixtures" by Burton, G., Corn, M., Gee, B. L., Vasallo,
C. and Thomas, A. P. resulted and appeared in the AMA Archives of
Environmental Health 18, 681 (1969). (Appendix I.) Efforts on
this Contract then shifted to studies of synergism in cats ex-
posed to the same aerosol-irritant gas mixture as was used in the
human studies. In addition to the presence or absence of response,
we were interested in the mechanisms associated with the response.
Quarterly Progress Reports have been submitted since the in-
ception of this Contract. The publication referenced above sum-
marized the work accomplished during the initial 18 months of the
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2
Contract. The purpose of this report is to summarize efforts
during the latter 18 months of the investigation. Progress
during this period was exclusively associated with synergistic
studies utilizing cats as test animals. The work reported here
is scheduled for presentation at the 10th Air Pollution Medical
Research Conference to be held in New Orleans, October 5-7, 1970.
The paper is entitled "Response of Cats to Inhaled S02 and S02~
NaCl Aerosol Mixtures in Air" by M. Corn, N. Kotsko, D. Stanton,
and W. Bell. The presentation will be a summary version of data
and discussion presented here.
B. Background for Inhalation Studies Using Cats as Subjects
The biological assay procedure for air pollutants, as origin-
ally developed by Amdur and Mead ^ , utilizes guinea pigs as ex-
perimental animals. The results of work by Amdur and her co-
workers is reviewed in the document Air Quality Criteria for
12)
Sulfur Oxides . The more than a decade of work by Amdur, in
which guinea pigs have been exposed to a variety of gaseous and
particulate pollutants, provides the most extensive body of in-
formation available on the response of an animal species to air
pollutants. The data relative to human response to mixtures of
pollutants, as judged by alterations in parameters of pulmonary
mechanics,- have not substantiated the findings in guinea pigs.
The studies on humans are few in number and are contradictory,
as discussed by Amdur in a recent appraisal of sulfur d.ioxide-
(3)
aerosol mixtures and their effects on animals and man . Because
of heavy reliance on the guinea pig assay system and the diff.i-
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3
culties inherent in extrapolating these data to man, or even
in drawing conclusions from these data relative to effects of
these systems on man, it was considered appropriate to study
the effects of these mixtures on another species.
A reasonable and appropriate question is "why select the
cat as the species of choice in these studies?" A series of
investigations by Widdicombe^'^'^ and Nadel^7'®' delineated
the mechanisms of bronchoconstriction and peripheral airway
constriction in cats. Thus, studies of response to pollutant
gas and aerosol mixtures in cats promised to answer whether the
responses reported in guinea pigs occurred in other animal
species. Also, if they occurred, the mechanisms of action
could be investigated by isolating previously studied mechanisms
and pathways of response by means of well developed experimental
techniques. The investigation reported henewas a follow-up to
this reasoning. We report on the effects of sulfur dioxide
alone, and in combination with sodium chloride aerosol, on the
pulmonary flow resistance and lung compliance of cats. In ad-
dition, results will be reported for pathological examination
of lungs initially rapidly frozen with iquid Freon following ex-
posure to pollutant free or to pollutant laden air. Experimental
methods will be described and this will be followed by results
and discussion.
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4
II. EXPERIMENTAL METHODS
A. Pollutant Aerosol and Gas Concentration
Pollutant mixtures for the exposures were produced using a
portable aerosol and pollutant gas supply apparatus designed
and constructed for this study (Fig. 1).
Medical-grade compressed air was passed through activated
carbon and silica gel. The stream of air was metered by the
use of calibrated orifices, before entering the Dautrebande
D^qI generator or the Venturi tube for mixing with aerosol and
gas. Sulfur dioxide gas was supplied to the Venturi throat by
a syringe driven by an infusion pump. The Dautrebande D^Q1
aerosol generator was filled with isotonic NaCl and placed in
an opening at the base of the Venturi tube. The salt solution
was replaced every 15 minutes to prevent a significant increase
in Nad concentration clue to the evaporation of water.
The mixture cxi ted from the Venturi mixing tube into a ro-
sorvoi r balloon, where it was either exhausted, or withdrawn
by the Harvard pump.
All components of the system, with the exception of the
balloon, were of stainless steel, rigid plastic, or Teflon.
A three way valve at the entry to the Harvard pump could be
set for pollutant mixture or room air entry to the pump. The
Harvard pump was equipped to permit the setting of tidal volume
and breathing frequency. The most commonly used settings for
these parameters were 75 ml and 20 cps, respectively. The in-
spiratory stroke of Lhe pump was under positive pressure. The
animal expired under Lhe driving force of lung elasticity.
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5
FIGURE 1
SCHEMATIC OF POLLUTANT GENERATION APPARATUS
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b -cy
Harvard
Pump
Exhaust
1X3
Schematic of pollutant generation ap-
paratus. A, Valves; B, "catch-all"
air cleaner; C, silica gel; D, Milli-
pore HA filter; E, Critical orifice;
F, pressure gauge; G, SO2 inlet; H,
mixing balloon; I, Herschel-Type Venturi
tube; J, Dautrebande D30I; K, Motor
driven syringe; L» Medical grade com-
pressed air; triangle, flow direction.
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6
B. Pollutant Gas and Aerosol Sampling and Analysis
Samples for measurements of aerosol and pollutant gas con-
centrations were withdrawn from a stainless steel port in the
exhaust line following the balloon reservoir. It was ascer-
tained that concentrations measured above the tracheal cannula
did not differ from those withdrawn at the former site.
1. Sulfur Dioxide
In order to determine S02 concentration, 0.76 liters/
min. of the pollutant mixture was drawn for three minutns into
a midget impinger containing 10 ml of West-Gaeke reagent. The
samples were then analyzed spectrophotometrically using the
(9)
West-Gaeke method with the Pararosaniline modification spe-
i 10 '•
cified by Pate '. The high sulfur dioxide concentrations in
the experimental protocol required additional modifications in
the analytical method, as follows.
a) A 1 nr. 1 aliquot was removed from the original 10 ml
sample and was diluted with 10 ml of unexposed absorbing re-
agent. The 9 ml and 1 ml aliquots were then prepared accord-
(9)
ing to the original West-Gaeke procedure
b) A calibration curve was prepared using standardized
solutions of sodium bisulfite, which ranged in concentration from
0.1 to 5-0 ug of SO2 per ml. The solutions were standardized by
the iodometric titration method described by the Intersociety Com-
mittee for Ambient Air Sampling and Analysis . A new calibrat-
ion carve was prepared whenever a new stock dye solution was used.
A typical calibration curve is shown in Figure 2. All calibration
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7
FIGURE 2
CALIBRATION CURVE FOR S02 USING MODIFIED
WEST-GAEKE PROCEDURE
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0.4
a> 0.3
0.2
B&L Spectronic 20
560 nm
Amax ~
Path Length = 150 mm
8
5
4
6
9
10
2
3
Total /ig S02 in I2mi Volume*
* 12ml includes 10ml. absorbing reagent +1ml dye + 1ml formaldehyde
CALIBRATION CURVE FOR
THE DETERMINATION OF
SULFUR DIOXIDE USING
THE WEST-GAEKE METHOD
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8
curves adhered to Beer's Law in the absorbance range less than
0*700. If a 9 ml sample yielded an absorbance value greater
than 0.700, it was discarded and the 1 ml sample was analyzed.
The concentration of SC>2 in pg SC>2 per ml was calculated as
follows:
VT x Absorbance
vg S02 per ml = slope x vp
where VT = total volume of solution, ml
V„ = fraction of original sample analyzed
The total volume of the 9 ml sample was 11 ml, which consis-
ted of 9 ml of the original sample, 1 ml of dye and 1 ml of for-
maldehyde- The 1 ml sample contained a total volume of 13 ml,
which consisted of 1 ml of the original sample, 10 ml of unexposed
absorbing reagent, 1 ml of dye and 1 ml of formaldehyde.
The concentration of Bulfur dioxide was converted to Parts Per
Million (ppm) in air as follows:
PPM S02 «
where 382 = Conversion factor for yg/ml to ppm at 25°C, 7G0 mm.
C = Concentration of SC^ in yg/ml
R = Sample flow rate in cc per minute
T = Sample time in minutes
It should be noted that whenever sodium chloride was present
in the system, sampling for sulfur dioxide was performed by first
drawing a sample through HA Millipore filter paper to eliminate
sodium chloride interference. Several calibration runs indicated
that the loss of sulfur dioxide on the filter paper was negligible.
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9
2. Sodium chloride Aerosol
The concentration of sodium chloride aerosol was deter-
mined by withdrawing the exposure mixture at 21 liters/min. for
20 minutes through HA Millipore paper, leaching the salt by
filter immersion in distilled water, and analyzing electrical
conductivity. A calibration curve was prepared using reagent-
grade sodium chloride. Because of the length of time required
to sample for the sodium chloride aerosol, this was done at the
end of the exposure periods. Several nonexposure and postexpos-
ure checks found the concentrations to be very consistent over a
period of several hours.
The particle size distribution of the aerosol was determined
by first sampling with an oscillating thermal precipitator onto
a carbon-coated glass coverslip. The carbon film was transferred
to a 200 mesh electron microscope grid prior to obtaining photo-
graphs with an electron microscope. The particles were sized
using a Zeiss TGZ3 particle sizing unit. The particles were all
smaller than 0.40 ym by weight; the mean size and standard deviat-
ion were 0.25 ym and +0.01 ym, respectively. (Figure 3.)
The concentrations of SC>2 gas and NaCl aerosols used in these
studies will be cited in the Results and Discussion section of
this report. However, it is appropriate here to indicate the
variations in concentrations used in these studies. LOW sulfur
dioxide concentrations were 15-25 ppm. HIGH sulfur dioxide con-
centrations were 30-40 ppm. Sodium chloride aerosol concentrat-
3
ions were 9-10 mg/m .
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10
FIGURE 3
CUMULATIVE PARTICLE SIZE DISTRIBUTION CURVE FOR TEST
AEROSOL SIZED AT 32,000x
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I
1
I
I
I
W 60
i
1
I
i
I
I
i
I
I
I
i
I
I
I
I
i
0.10 0.15 020 0.25 0.30
PARTICLE PROJECTED AREA DIAMETER, p.M
035
0.40
CUMULATIVE PARTICLE-SIZE DISTRIBUTION
CURVE FOR TEST AEROSOLS (NaCl),
SIZED AT 32/OOOx WITH ZEISS
TGZ-3 AND ELECTRON MICROSCOPE
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11
A representative time-concentration diagram for each pollu-
tant during a single experiment is shown in Figure 4 (Cat No.
1610).
C. Animal Handling and Preparation
Upon receipt cf animals a routine examination was made to
determine the presence of gross abnormalities. Animals with ab-
normalities were returned to the supplier; all other animals were
weighed and were then injected with feline pneumonitis vaccine.
(Veterinary care or consultation was available when needed.) An
initial isolation period of 2 weeks was observed.
All animals were caged, fed, and attended in accordance with
the rules and regulations of the United States Department of
Agriculture and Federal Act of August 24, 1966 (P.L. 89-544).
A trained technician observed, weighed and kept a daily record
of any changes that occurred. At the conclusion of the isolation,
period animals were permitted to exercise daily.
Food and water were removed from an animal cage 18 hours prior
to inhalation exposure. An examination was performed for symptoms
of diarrhea, diuresis, conjunctivitis, etc. The entire ventral
and cervical region of the cat was then shaved and a vacuum was
used to remove excess hair.
Nembutal (30 mg/Kg, intraperitoneally) was used to anesthetize
adult cats weighing 2-5 Kg. Occasionally additional nembutal was
required. We preferred to keep the cats in a light surgical anes-
thesia (Stage III). A check of the pedal and corneal reflexes
were made to determine if additional nembutal was required. The
booster dose, if required, was given intravenously in diluted
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12
FIGURE 4
TYPICAL VARIATIONS IN POLLUTANT CONCENTRATIONS
DURING AN EXPERIMENT
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50
45
i
40
35
30
25'
i
20
15
10
5
~ -High Concentration SO2
a-Low Concentration S02
o - S02•+ NaCI: NaCI Cone: 9-IOmg/M3
I I I I I 1=
5 10 15 20 25 30
Time, Minutes
TYPICAL SYSTEM PERFOR-
MANCE: SO2 EXPOSURE
CONCENTRATION VS. TIME
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13
r;aline solution. When an animal did not relax, Gallamine Tri-
ethiodide, a muscle relaxant, was administered. It produces a
nondepolarization block at the neuromuscular junction. The
dosage was 0.05 mg/Kg, intravenously.
Two surgical procedures were used. In the first method, a
tracheotomy was performed by using a Bard Parker #3 holder with
#15 rib back blade. A 1 inch incision was made approximately
20 mm below the larynx in the center of the ventral region of
the throat. The muscle was separated by using two small hemo-
stats which were spread in opposite directions until the trachea
was visible. A slichtly larger hemostat was inserted under the
trachea and was then lifted on the opposite side, where at this
time a 6" length of suture was attached. This hemostat was left
in position. A small horizontal cut was made between the carti-
lage rings of the trachea and a suitable size cannula was in-
serted. The cannulas which were used were 6.35 mm i.d. and 7.98
nun i.d. with 7/16" diameter side air tube. The hemostat was
withdrawn after bringing 3" of the suture to the opposite side
of the trachea and tying the cannula to hold it intact. In vago-
tomized cats we tied off the vagus nerve before inserting the
cannula. The side air tube of the cannula was connected to a
Fleisch Pneumotachograph (0), which in turn was connected to a
Model #60 7 Harvard Animal Breathing Pump.
The second method utilized similar procedures, but in this case
an endotracheal tube was placed at the entrance of the larynx. The
epiglottis was sighted with the aid of a laryngscope and was then
held open by a small hemostat. A #16 Foregger endotracheal tube
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14
(i.d. 2.5 mm, o.d. 5.3 mm), previously interlined with Teflon
and having a built-in cuff, was then placed into the mouth of
the larynx and the hemostat was released from the epiglottis.
The cuff was inflated, clamped with a hemostat, and the tube
was connected to the air pump in the usual manner. Whenever
excessive mucus was found, suction was used to remove it.
A third and final preparation was used where a tracheotomy
was initially performed, as described in the first method. A
second cannula (same size) was inserted to provide a pathway
to the nasopharyngeal chamber of the animal. The side air tube
of the cannula was connected to an exhaust outlet. A face mask
made of Lucite and anatomically sculptured for perfect fit was
placed on the animal's face and was held in place with adhesive
tape. The Teflon tubing nipple of the mask was connected to a
small pump for flushing.
Preparation for intrapleural catheter insertion was initiated
by a 5 mm incision in the right lateral thoracic region between
the fourth and fifth rib. We used two small hemostats to probe
and spread in opposite directions until we entered the intra-
pleural space. The hemostat was held in position immediately
upon entry into the thoracic cavity. A #10 Malecot intrapleural
catheter (.089" i.d,) was clamped onto the second hemostat and
in a concerted movement one hemostat was withdrawn and the other,
with the attached catheter, was inserted. The incision was sealed
with wound clips. The catheter was connected to the side arm of
a Statham differential strain gauge (Transducer Model No. PM 5 +
0.2-350). The othor arm of Ihe strain gauge was connected to an
opening on the side of the tracheal cannula.
-------
15
In order to record blood pressure, intramedic polyethylene
tubing (.045" i.d.) was inserted into the femoral artery and
was then connected to a Statham strain gauge (Model No. P2 3Db
series pressure transducer). The pressure dome of the transducer
was filled with 1/200 solution of heparin and sodium chloride.
The same size catheter was inserted into the femoral vein for ad-
ministering drugs. Blood loss from surgery was minimal.
At the conclusion of; inhalation exposures, the cat was sacri-
ficed by administering an additional dose of nembutal. The thorax
was opened by making a midline incision in the ventral thoracic
region. The muscle was separated, costal cartilage dissected,
sternum and eight pairs of ribs were removed. Portions of all
lung lobes were exposed. We applied a modified Staub freeze tech-
(121
nique ' using Freon 12 (Dichlorodifluoromethane). Freon 12 was
chosen because it was not hazardous, it required no extensive pre-
parations for use, and good frozen sections were obtained.
D. Determination of Pulmonary Flow Resistance and Lung Compliance
The surgical preparations described above were followed by the
hook-up of Statham transducers to the Electronics for Medicine
Model DR-8 amplifiers for oscilloscope readout. The signals mon-
itored and their respective transducers are shown in Table 1.
The signals from the DR-8 amplifiers or integrators could be
visually read on an integral oscilloscope or recorded on LW-2 7,
18 cm photographic paper. A second oscilloscope provided visual
display of R^ and loops. These could also be permanently re-
corded on the photographic paper. Dry records were obtained in
four seconds by means of a Rapid Writer attachment.
-------
TABLE 1
PARAMETERS RECORDED ON THE ELECTRONICS FOR MEDICINE UNIT AND
ASSOCIATED TRANSDUCERS
Parameter
Transducer
Pressure
Range
Intrapleural
Pressure (TPP)
Statham Model No- PM 5 + 0.2-350
Serial No. 12394
+ 0.2 psid
Air Flow (V)
Fleisch Pneumotachograph with Stat-
ham Model No. PM 283TC + 0.15-350
+ 0.15 psid
Volume of Air (V)
Signal from V is electronically in-
tegrated
Blood Pressure
Statham Model No. P23Db. Serial No.
11680
-------
17
Representative sweep and loop tracings from the Rapid Writer
are shown in Figure 5.
Figure 6 is a photograph which shows the test cat connected
to the Harvard Pump and the pneumotachograph in position.
In these studies animals were ventilated at 50-80 cc per
stroke at a frequency of 18-21 strokes per minute. Thus, on
the basis of an average tidal volume of 26 cc for the cat, these
animals were hyperventilated.
When using oscilloscope loops* the total lung resistance was
measured by subtracting a voltage proportional to lung volume
change (and this proportional to compliance pressure) from the
pressure axis of a pressure flow trace recorded on the oscillo-
scope screen^^. The voltage subtracted was sufficient to close
the loop. The slope of the line resulting from closing the loop
represented total lung resistance, which includes airway resist-
ance and the viscous resistance of the lung tissue.
Calibration of all transducers was performed at the completion
of each experiment. The correspondence between water or mercury
manometers as primary standards and the LW-27 photographic paper
readout of BP and TPP was recorded. Air Flow (V) was calibrated
by utilizing compressed air and a rotameter calibrated against a
wet test meter. Volume was calibrated by alternately depressing
or withdrawing the barrels of two opposed 100 ml syringes in a
closed air loop with the Fleisch Pneumotachograph; 20 ml increments
of volume yielded a step function on the record chart. Loop signals
were calibrated in a similar manner, except that signal deflections
were measured directly on the oscilloscope face.
-------
18
FIGURE 5
REPRESENTATIVE SWEEP AND LOOP TRACINGS USING E FOR M
RAPID WRITER AND LW-27, 18 cm PHOTOGRAPHIC PAPER
-------
19
FIGURE 6
PHOTOGRAPH SHOWING CAT ARTIFICIALLY VENTILATED BY
HARVARD PUMP
-------
A Statham Transducer (TPP)
B Fleisch Pneumotachograph
C Statham Transducer (V and V)
D Harvard Pump
-------
20
tThe dead space of the tracheal cannula and Fleisch Pneumo-
tachograph, i.e. volume from bifurcation above Pneumotachograph
leading to Harvard pump inlet or discharge, to the trachea of
the test animal, was 4.7 cc. A correction was subtracted from
each value of total lung resistance in order to correct for the
resistance of the tracheal cannula.
E. Conduct of Experiments
Each animal acted as his own control with respect to resting
state values of TPP, V, V, R^, and C^. The criterion for signi-
ficant changes in these parameters following inhalation of pollu-
ted air was that the values of these parameters after, exposure
should be different from the values of these parameters in the
same animal before exposure. This approach requires that care
be taken to ensure that the animal is in a stable resting state
prior to being challenged by a polluted atmosphere. Another
criterion of thene studies was that following exposure an animal
had to return to his initial, preexposure values of these para-
meters before he was challenged with another polluted atmosphere.
These are stringent experimental criteria which resulted in long
experiments.
Immediately following, surgical preparations the animal was
maintained in a resting state for approximately one half hour.
This was followed by a 15 minute control period, with recorded
records at five minute intervals and continuous sweep visual dis-
play. The animal was then tested by mechanical stimulus to ensure
the intactness of the vagally mediated reflexes for control of
(14)
airway constriction . Initially, the vagii were surgically
-------
21
isolated and an electrical stimulus was applied, but the mechan-
ical stimulus was judged to be equally effective and less trau-
matic. A further control period of 15 to 60 minutes followed
the mechanical stimulus test. If the vagii were not responsive,
as judged by an immediate increase in R^, then anesthesia was
too deep and the animal remained in a resting state until a pos-
itive test was obtained for intactness of vagal pathways. This
procedure of testing was repeated prior to the first, and after
each succeeding pollutant challenge.
The order of exposures in these studies was varied in order
to rule out the possibility of a long-term effect due to initial
exposure to High S02, for instance. Thus, certain animals were
initially exposed to High SOj (following control period), and
then to Low SO2 or the Sf^-aerosol mixture. All orders of ex-
posure were used. After initial exposure to High SC>2, a 1-2 hour
resting period was required to permit the animal to meet the
criterion establishad for return to initial resting values of
parameters.
Another series of experiments was performed to determine if
receptors which could affect airway size were being bypassed by
introduction of pollutant gases (in breathing air) by means of
the tracheal cannula. These tests were made with an endotracheal
catheter. In this case, the animal was ventilated by the Harvard
Pump and the tracheal cannula, but room air (for control) or pol-
lutant laden air was simultaneously flushed through the endotra-
cheal catheter by means of a small pump delivering 2.4 cc/stroke.
-------
22
Only Low SC^ concentrations were delivered in these studies.
In a similar manner, a series of tests was performed to de-
termine if receptors in the nose could cause airway constriction.
The usual procedures were followed, but another cannula was in-
serted back to back to the cannula flushing upwards into the
mouth. A mask was placed over the nose and mouth. A small pump
ventilated the mask while the second cannula served as the ex-
haust. Thus, the airway above the tracheal cannula was being
flushed via the nose and mouth. The lower airways received
breathing air or pollutant gas via the original tracheal cannula.
Low and High S0o in air were used in this series of experiments
(Figure 7) .
F. Treatment of Data
Values of R_ and C, were calculated from sweep tracings of
Xi li
(1^
V, V and TPP as described in the original method ' , or the
values were obtained from reading recorded loops. R_ and CT
Li Lt
values w^re then graphed as a function of time. Although con-
tinuous records were made, it was necessary to establish the
intervals for transcribing data in order to show experimental
trends. Figure 8 is a representative graphical summary showing
values of --R and CL at five minute intervals. In this case each
point represents a series of breathing cycles from the sweep
record and clearly shows the stability of these parameters dur-
ing control periods.
Table 2 contains the numerical results obtained from the ex-
periment on Cat #1610.
-------
23
FIGURE 7
CANNULA ARRANGEMENTS FOR EXPOSURE VIA TRACHEAL CANNULA AND FOR
ABOVE AND BELOW TRACHEAL CANNULA
-------
24
FIGURE 8
GRAPHICAL SUMMARY OF VARIATIONS IN R. AND CT DURING
Li L
AN EXPERIMENT
-------
Pol luton1
Mixing
Chamber
Pneumo-
tachograph
Tracheal
Cannula
Harvard
Pump
Solenoid
Valve
(a) Via Tracheal Cannula
Pollutant
Mixing
Chamber
Infusion
Pump
Solenoid
Valve
Endotracheal
Catheter
Tracheal
Cannula
Harvard
Pump
Pneumotachograph
(b) Via Trocheol Cannula and Endotracheal Catheter
Pollutant
Mixing
Chamber
ri
+f-
Hqrvard
Pump
Mask
Exhaust
Infusion
Pump
Double
Cannula
Solenoid
Valve
from
Harvard
Pump
Tracheal
Cannula
Pneumotachograph
(c) Via Naso-pharyngeal Chamber
<33-4.
-------
B i85.4
0144.3
Q 160.4
~ 124.2
0132
20
I
40
38 -
o ~ Pulmonary Flow Resistance
0-—--Q Lung Compliance
EXPOSURE RESPONSE PROFILE:
AN I MAL NO. 1610
36
u
a>
34
- <
u
z
\- <¦
r
u
LU
U 2
o
r>
Z
£
CO
S02
(23.3 ± 0.4 ppm)
EXPOSURE
CONTf
S02
(25.2 ± I.Oppm)
4 NoCI
(I0±02mg/M5)
EXPOSURE i
CONTROL
Time,
m
— 3
zb|
§F
*r
i
i
i
CONTROL
NaCI
(I0±0.2mg/M3)
EXPOSURE
t -
CONTROL
i
o—o |
O-G
Q-0
I
o-o
o
r
«£>—O
~-Q
so2
(39.4 ± l.9ppm)
EXPOSURE
O
a:
o
u
u-
140
Minutes
160
180
200
16
14
St,
X
E
a
c
a
10 =
E
o
o
220
240
260
-------
25
Final calculations are based on data from the final fifteen
minutes of the control and exposure periods. Other time periods
were evaluated, but the last fifteen minute period proved to be
the best indication of response. The table shows the mean and
the standard arithmetic deviations of parameters during this time
period. The percentage change in parameters noted in Table 2 was
calculated from control period values as a baseline. Thus,
„ -Value Following Challenge-Control Value,
% Change - ( ; control Value ' 100
Tabular and graphical summaries of individual experiments con-
ducted during this study are contained in the Results and Discus-
sion section of this report.
Before an animal's response was termed "significant" it was
necessary to compare and CL values obtained during the last
fifteen minutes of the control and exposure periods. The compari-
son was based on a modified Student t-test for the difference of
means. The degrees of freedom (d.f.) for the test was calculated
from the variances and sample sizes. Thus,
t - X2 ~
+ s22/n
2
[(S12/n1) + (S22/n2)]2
(S12/n1)2/(n1 + 1) + (S22/n2)2/(n2 + 1)
where mean values are designated x^ and x2, the standard deviat-
ions are and S2, and sample sixes are n^ and n2.
The level of significance accepted as meaningful with the t-
test was P < 0.01 (two tailed test).
-------
TA3U" 2
Cat Ho. IfciO
RESPONSE TO VARIOUS STIMULI E*PSESSED AS PERCENT CHA!!3E RELATIVE TO COMTROL VALUES*
Pulmonary Flow Resistance
(b)
Cont r01
Kn-:S.
Stir..
V:
Cho ¦ J
Contr 0 i
Low
S0?
u
".-a- g-:=
Con tro1
Mech. K
St in. Change
S02 +
Controi NsC1
Change
Control
Mech.
St i m.
y.
Change
25.5
7? .h
67U. 1
75.5
25.5
25.5
?k.°
2
?» . ?
-' 6 c
-35.5
^5.5
1^J.3 -65.9
25.5
25.5
27.6
2°.6
25.5
8.2
12.2
0
25.5
25.5
160. 4
529.0
Meant 2k.0
S.D. 2.2
iSS.b
25-5
0
2i+. 5
3.0
25.5
0
1M+.3
25.5
0
27.2
1.6
25.5
0
' 0O.4
reflex
INTACT
A K. 5 .
REFLEX INTACT
A N.S.
REFLEX INTACT
Lung Compliance 'c^
C\
L 0 ' t r 0 '
Mech.
St'".
J,
Chsnge
Con f J 1
Low
so2
Change
Contra
!'?ch. /:
S t im.Change
so2+
Control NaCl
%
Chan.^-
Control
Mech.
S t i m.
%
Change
= 7
^3
y •
h
3.3
9.3
3.3
7.7
7.:
-7.2
-7.2
-=.l4
5.3
3.3
b.1 -50.6
8.3
8.3
7.6
7.6
7.6
-8.I4
-8.U
-S.h
8.3
8.3
k.2
e = - r ~. 3
i.D. 0
5.
h
8.3
0
7.6
0. i
p<0.01
8.3
1
'.3
0
7.6
0
P< 0.01
8.3
0.
h.2
Sequence oF>
CSallen^e
(D
(?)
(3)
(«~)
(5)
*C0.05)
(b) Pulmonary Flow Resistance* Cm H20/l/sec.
fc) Lunq Compliance, mi/cm
-------
TA3LE 2 (Continued)
Cat rlo. 1610
RESPONSE TO VARIOUS STIMULI EX JESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
(b) ' *
Cootro1
NaCI
Change
Control
Mech.
Stim.
-j
Charon'
Cont rot
Hi gh
o0?
%
Change
Mech. V-.
Control Stim. Changs
25-S
1 ?5. ^
27.f
^.3
26.6
3.2
n.o
27.6
26.6
12U.7
:35?.3
25.5
25.5
39-1
30.7
33
53.3
20. It
29.U
25.5 132 M7.6
V.ear t 25 . 1
S.O.. 0
2.7. ^
0.8
27.1
0.7
12U.7
25.5
0
3^.3
*.3
25.5 132
£
¦•¦. S .
REFLEX INTACT
A
N.S.
REFLEX INTACT
Lung Compliance ^c^
Contro 1
NaCl
>-
Change
C 9 *. t ** O 1
Pec- .
Stim.
Cna-ge"
Conf.jl
Hi ah
SO2
%
Change
Mech, %
Control Stim. Change
8.3
'1.0
7.5
7.5
7.3
-8.0
-3.0
-10.U
7.8
7.7
U.2
-'0.8
7.3
7.8
7.6
7.5
7.5
-2.6
-3.8
-3.8
8.1 5.1 -37.0
^lean* ^2
S.D. 0.2 •
7.^
0. 1
7.7
0. 1
it.2
7.8
0
7.5
0.1
8.1 5.1
P<
0.05
P<
0.05
Sequence of^ j
1 Cfial 1en0.05)
(b) Pulmonary Flow Resistance! Cm H20/l/sec.
fc) Long Compliance, ml/ctr, HjO.
-------
28
G. Pathological Procedures
Six weeks after fixation tissues were removed from freezer
and Carnoy's fluid poured off. The Storey and Staub^^' method
was used to process and stain most of the lung tissues except
for a modification as follows:
1. Nitrocellulose embedded tissues were sectioned 75 pra
thick on a Reitchert sliding microtome. Using Lundy's method,
serial sections were stapled in sequence, approximately 5 mm
apart (by means of an office stapling machine), on a strip of
500 gauge polyethylene film, cut slightly wider than the width
of the sections. The length of the strips was determined by
the size of our staining dishes (Pyrex Baking Dish 5" x 9").
After the tissue was stained, sections were detached from the
film with scissors and mounted in sequence on numbered slides.
Strips of polyethylene film holding sections not immediately
required for staining were rolled up and stored in 70% alcohol.
In order to obtain thin sections, a small piece of each
lung tissue was put into Bouin's fluid for 24 hours for fur-
ther fixation. A routine manual process was used to obtain
paraffin blocks. Blocks were sectioned 5 um on an American
Optical rotary microtome. Serial sections were stained w.ith
Harris Hematoxylin and Eosin and mounted on glass slides v^ith
permount.
We photographed serial sections 5 ym thick and 75 iim thick
with a Zeiss photomicroscope. To obtain a total estimated mag-
nification of 130x, a planachromatc- 2.5x objective with an
N.A. = 0.08, optavar = 2.Ox, intermediate camera magnification
-------
29
of 3.2x and photographic enlargement estimated at 8.Ox was used.
A calibrated field finder was used in returning to the same
photographic field of each slide in the series.
Measurements were made of the alveoli on the enlarged prints
of thick tissue sections. We noted in our findings that there
were no significant changes in the sizes of the small conducting
airways of cats which had shown small rl and small CL changes.
In an attempt to measure the same segment of lung lobe of
each cat we measured 2 cm from the tip of the third lobe of the
right lung and removed that portion of the lobe for frozen
sectioning and for comparison. Biological factors such as
weight and size of the lungs presented a problem. We questioned
whether we could be sure that we were in the same segment of
the lobe, when some of the lungs were larger than others. De-
spite this obvious flaw, we cut the same distance from the tip
of tho same lobe of each animal to obtain comparable sections.
We realized, however, that we had encountered a source of error
in using a method of measurement on a histologic section.
Thin lung sections were studied, of cats that had been chal-
lenged with SC>2 in the air and S02 + NaCl aerosol in medical
grade breathing air. The absence of comparable changes
in cell structures suggested that small R_ changes and small
Li
CL changes could not be detected histologically.
-------
30
III. RESULTS AND DISCUSSION
All calculated results for individual experiments are con-
tained in tabular and graphical summaries in this Section. The
results presented were obtained by extracting data from continu-
ous records as described in Section II F., above. Results are
presented for a total of twenty-nine complete experimental pro-
tocols in which twenty-nine different cats were used. A dis-
cussion of this vast amount of data requires that a simple sum-
mary be used to present findings. The reader can examine cal-
culated results of individual animal experiments to substantiate
generalizations made in this discussion.
A. Changes in Pulmonary Flow Resistance and Lung Compliance in
Cats Following Pollutant Challenges
Table 3 summarizes the challenge atmospheres which produced
significant changes in pulmonary flow resistance or lung compli-
ance when the pollutant mixture was administered via tracheal
cannula. Table 1 i.ti a aimilnr summary for pollutants administered
via endotracheal catheter and via double cannula to products pol-
lutant flushing of the nasopharyngeal chamber and any receptors
above the trachea cannula. First, the data suggest that with the
cat, approximately 20 ppm SC>2 in air are required before any ani-
mals show significant alterations in R . Prior to the studies
J_i
reported here, it had been shownthat pure SC>2 delivered into
the lower airways and lungs during a single respiratory cycle in-
creased R^ (mean, + .246 percent; p < 0.05). The animal returned
(7)
to control .levels within one minute . The work reported here
-------
31
indicates that with the same physiological preparation approxi-
mately 20 ppm SC>2 in air are required to trigger this response—
and at this concentration only two animals in twenty responded.
One animal in twenty showed a significant decrease in R at this
concentration.
It is interesting to compare concentrations of SC^ in air
required to cause bronchoconstriction in different species.
Frank, et al. demonstrated a significant increase in resis-
tance to air flow in volunteers exposed to 5 ppm. This finding
is consistent with that of Burton, et al. (Appendix I) of per-
haps one out of ten "human reactors" to approximately 3 ppm S02
(17)
in air. Balchum, Dybicki and Meneely exposed ten anesthe-
tized dogs to concentrations of SOj in air ranging from 1.8 to
148 ppm for periods from 30 to 40 minutes. Increases in the non-
elastic resistance to breathing ranged from 150 to over 300% and
these increases occurred within nine seconds after the onset of
breathing SC^; increases disappeared as quickly following the end
of exposure. Exposures of guinea pigs to SC>2 in air for one hour
results in a 10% increase, in preliminary flow resistance at 0.16
(18)
ppm . The guinea pig, as used by Amdur, "may be the acci-
(3)
dental analog of the sensitive segment of the population".
The results reported here suggest that the cat, as used in our
preparation, is an analog of the more resistant segment of the
population.
<151
An aspect of our studies which was stressed by Frank, et al. '
and Burton,, et al. (Appendix I) in studies involving human expos-
ures but was not stressed in studies employing dogs or guinea pigs,
LIBRARY / EPA
Na'ional Environmental ReasarcJl
•20-; S, W. 35th Sit act
C-rvnll'- QT?3Q
-------
32
is the great variability of response of individuals. In our
studies, "reactors"' were characterized by large variability
of response in RT and CT and hypersensitivity during preparat-
L Li
ion. Examination of graphical summaries of results of expos-
ures will demonstrate the great variability of response for
animals with cervical vagosympathetic nerve conduction intact.
Two other characteristics of response should be noted for
their contrast with guinea pig studies. Our animals returned
to control levels shortly after exposure, although we often
waited for an extended period to reduce the range of variation
about the mean RT or CT following exposure, i.e. variability
Li 1j
about the mean was greater following exposure, which we did
not desire. We chose to permit the animal to settle down. The
guinea pig, on the other hand, returns slowly to control levels
after exposure. As noted above, following exposure human sub-
ject;; and dogs alno return rapidly to control vu'Iuum of rc.uins-
tance to air flow.
In animals showing changes in pulmonary I: low resistance, we
confirmed the effects of cooling the vagii, injection of atro-
pine or severing the vagii, on blocking these changes, as re-
ported by Nadel, et al. ^
Table 4 summarizes results collected to focus on the site^
of receptors responsible for bronchoconstriction or periphe-
ral airway constriction. These results relate to findings
of nearly total uptake of SC>2 in air in the nose and upper air-
(19 ?0) (21)
ways in animals '~ and in human subjects . Less than
1% of the* inhaled concentration of S02 in air is estimated to
-------
33
reach the larynx and more distal airways in man^20^. The en-
dotracheal catheter and double cannula were used in these
studies to determine if the number of animals responding in-
creased, or the degree of response increased in respondents
when the pollutant mixtures were administered via these path-
ways in cats. Three animals were exposed with the endotracheal
catheter and two with the double cannula. Unfortunately, these
experiments must be contrasted to findings in twenty cats where
a tracheal cannula was used for delivery of pollutant mixtures.
However, comparison of Tables 3 and 4 suggest that delivery of
pollutant via tracheal cannula did evoke fewer significant re-
sponses in Rr or CL , thus suggesting that certain receptors
L ii
were bypassed when pollutant was delivered by tracheal cannula.
Thus, our findings suggest that receptors in the nasal pharyn-
geal chamber and proximal to the tracheal cannula used hero can
increase total lung resistance diHtal to the tracheal cannula.
(22)
This finding contrasts with that by Nadel and Widdicombe
that mechanical irritation of the nasal mucosa did not change
total lung resistance in cats anesthetized with chloralose and
urethan. Additional cats should be studied to substantiate our
findings.
Small but insignificant changes in lung compliance were found
in a few animals following each of the challenges presented, in-
cluding one animal who showed a significant decrease in C follow-
L
ing inhalation of NaCl aerosol. These results suggest that the
physiological mechanisms generally delineated for upper airway
-------
34
and for peripheral airway constriction by acute challenges of
physical or chemical agents may not be completely independent.
Other investigators have suggested that a reflex mediated by
vagal efferent fibers could partially contribute to peripheral
(8)
airway changes . Alternately, the small quantities of pollu-
tants which penetrated the upper airways may be sufficient to
cause peripheral airway constriction, but this possibility, al-
(21)
though suggested elsewhere , seems remote to us as a mechan-
ism for peripheral airway constriction.
Finally, it should be noted that while upper airway changes
after inhalation of pollutants could be due to mucous secretion,
cooling of vagii, intravenous atropine or deep anesthesia blocked
these changes, thus suggesting that they were due to changes in
airway calibre.
D. Changes in Pulmonary Flow Resistance and Lung Compliance in
Guinea Pigs Following Pollutant Challenges
The rapid return of CT and R values in cats, dogs and man
Ij l.i
following exposures to pollutants used in this study differs
from the slow recovery of guinea pig pulmonary flow resistance
following similar exposures. Therefore, we used the exact ex-
perimental preparations described above to study the responses
of guinea pigs. Animals weighing approximately one kilogram
were used to permit insertion of a tracheal cannula; a difficult
procedure with small animals.
It was not possible to obtain valid data for guinea pigs
with our preparation. The animals secreted abundant mucous
-------
£
I'AiS . fi
i- *,.*?'<
e. ™ «"•
j«»5
;"2 o — :
? 3 *"»
ii*8
Uf* t '*
* i r ife
Hi h©«
2-vT a
= :l **'
¦c 2r , . i
I i i &
i*a? ^
BP Blood Pressure
TPP Transpulmonary Pressure
V Air Flow
V Volume
PL Pulmonary Flow Resistance
Lung Compliance
-------
?A3L£ 3
SU.'-'J-IARY OF R 3 AND C.b RESPONSES (P > 0.01) OF CATS EXPOSED TO POLLUTANT MIXTURES IN THIS STUDY"
(TRACHEAL CA-NNULA POLLUTANT DELIVERY)
Challenge
Low Concentration of SO2 in Aire
S02° and NaCI Aerosole in Air
NaCI Aerosol in Aire
High Concentration SO2 in Airt
Cat
Rl cl
. rl cl
rl cl
rl Cl
t," umber
+ +
+ + -
+ - + - j
1462g
X
1117
1112
X
X
1113
15f. 4
X
1566
X
1144
X
1593
X
1606
1611
1610
X
X
1633
1612
X
X
1609
1651
X
3 5 354g , i
32135g , i
14 86a,i
X X
X
14B7g,i
X
X
¦1676g,i
X
X
X
118 ih
X
1801h
X
1988h
X
X
X
1807h
X
X
X
aRL = Pulmonary Plow Resistance, Cm HjO/l/sec (+ denotes increase, - denotes decrease).
= Lung Compliance, ml/Cm H,0 (+ denotes increase, - denotes decrease).
cSO- in air concentration for all exposures, expressed as M~an + S.D. = 19.0 +_ 5.9 ppm.
J *
S02 in air concentration for all exposures, expressed as Kean + S.D. = 17.9 + 8.3 ppm.
^aCl aerosol in air concentration, expressed as Mean ~ S.D. = 10 *_ 0.2 mg/m^.
SOj in air concentration Cor oil exposures, expressed as Mean + S.D. ¦= 34.6 + 12.3 ppm.
9In the following experiments, ' the Low Concentration of S02 in air was the first challenge followed by Control Period
S02+NaCl Aerosol, etc.
V.
' In the following experiments, the High Concentration of SC. in air was the first challenge, followed by Control Period
;:aci Aerosol, etc.
LThese aninsis were characterized by extreme values of SO^ concentration.
-------
TABLE 4
SUMMARY OF R 3 AND C ° RESPONSES (P 0.01) OF CATS EXPOSED TO POLLUTANT MIXTURES IN THIS STUDY
(ENDOTRACHEAL CATHETER POLLUTANT DELIVERY)
n
Challenge ] SO-, in Air Via Tracheal Cannula
1
SO-, in Air Via Endotracheal Catheter^
C. J
SO2 in Air Via Both Sites0
Cat
Number
~ H -
~ ^ - ~
~ ci. .
2984
2206
53859
X
X
-
*
x
X
X
SUMMARY OF P..3 AND C.J" (NASO-PHARYNGEAL FLUSH WITH DOUBLE CANNULA)
Cnallenge
Low Concentration of SO2 in Air^
q
High Concentration SOj in Air'
Cat
Number
P C
L - + L -
RL Cl
+ L - + L -
2393
5674
3
RT = Pulmonary Flow Resistance, Cm r" 0/i/sec (+ denotes increase, - denotes decrease).
b
C^ = Lung Compliance, ml/Cm H2O (+ denotes increase, - denotes decrease).
cSO~ in air concentration for all exposures, expressed as Mean + S.D. = 18.2 + 1.9 ppm.
SOj in air concentration for all exposures, expressed as Mean + S.D. = 17.2 +_ 0.9 ppm.
eS09 in air concentration for all exposures, expressed as Mean + S.D. = 17.1 + 0.9 ppm
£ ^
XS02 in air concentration for all exposures, expressed as Mean + S.D. = 14.4 + 1.8 ppm.
^SOj in air concentration for all exposures, expressed as Mean + S.D. = 2 2.5 + 2.9 ppm.
-------
37
which required frequent withdrawal by catheter connected to a
suction source. The changes in pulmonary mechanics which stem-
med from mticous secretion in control animalr. would have over-
whelmed any changes associated with airway calibre alterations
due to pollutants. Mucous secretion under these conditions
cannot be compared to that which may occur during spontaneous
breathing during exposure to pollutants, the conditions for
13)
Amdur's studies . However, the slow return to control values
of Rl by guinea pigs strongly suggests mucous secretion as a
contributor to R , a hypothesis which could be easily tested
li
experimentally.
C. Pathological Changes in Cats Following Pollutant Exposures
Rapid lung freezing procedures and preparation of samples
were described above. While alterations in airway calibre
could be detected by this method following severe acute pollu-
(8)
tant challenges , it waa not possible to dei-.net. differences
in airway calibre in thick and thin lung sections of control
and exposed animals in the studies reported here. A control
animal was one previously exposed to SC^ or SC^-aerosol mixture
in air, but whose pulmonary flow resistance pubsnqn.onl-.ly returned
to the preexposure value. Figures 9 and 10 show the elose corre-
spondence between photomicrographs of thiol; lung sections from a
control and an exposed animal, respectively. Figure 11 .is a
photomicrograph of a typical thin lung section.
(2 3)
The work of Macklem and Mead stimulated these attempts
to detect changes in peripheral airway size v/hen alterations in
pulmonary flow resistance were present. Mae!: lem and Mead
-------
38
demonstrated that at high lung volumes, R increased and this
i_j
resistance was almost entirely due to that between airways
1.5-2.5 mm and the trachea in dogs. Thus, large changes in
peripheral airways resistance could go undetected by measure-
ment of Rl, which is insensitive to alterations in peripheral
airway resistance. Our studies show that careful morphological
examination of airway calibre are also insensitive to any
changes that may occur in the ranges of R increases cited
Li
here.
-------
39
FIGURE 9
PHOTOMICROGRAPH OF A THICK SECTION OF THE RIGHT LUNG LOBE OF A
MALE CAT (NO.. 1112). FROZEN IMMEDIATELY AFTER CAT HAD RETURNED
TO CONTROL STATE FOLLOWING 15 MINUTES PREVIOUS EXPOSURE TO 27
PPM S02.
-------
BLVEOLUS
ALVEOLAR DUCT
ALVEOLAR SAc
interAlveolar sep-
tum. X130 .
CO
-------
40
FIGURE 10
PHOTOMICROGRAPH OF A THICK SECTION OF THE RIGHT LUNG LOBE OF A
FEMALE CAT (NO. 1144). FROZEN IMMEDIATELY FOLLOWING EXPOSURE
TO 40 PPM S02 FOR 30 MINUTES.
-------
ALVEOLUS
ALVEOLAR DUCT
ALVEOLAR SAC
INTERALVEOLAR SEP
TUM. X130.
-------
41
FIGURE 11
PHOTOMICROGRAPH OF A THIN SECTION OF THE RIGHT LUNG LOBE OF A
MALE CAT (NO. 1610). FROZEN AFTER CAT HAD RETURNED TO CONTROL
STATE FOR 15 MINUTES FOLLOWING PREVIOUS EXPOSURES TO 40 PPM
so2.
-------
ALVEOLUS
ALVEOLAR DUCT
BRONCHIOLE
BLOOD VESSEL
CARTILAGE
EPITHELIUM
SMOOTH MUSCLE
X130
-------
42
REFERENCES
1. Amdur, M. 0. and Mead, J.: "Mechanics of Respiration in
Unanesthetized Guinea Pigs". Am. J. Physiol. 192 , 364
(1958) .
2. Air Quality Criteria for Sulfur Oxides. U. S. Dept. Health,
Education, and Welfare, Public Health Service, Consumer Pro-
tection and Environmental Health Service, National Air Pol-
lution Control Administration, Washington, D. C. January,
1969. NAPCA Pub. No. AP-50.
3. Amdur, M. 0.: "Toxicological Appraisal of Particulate Mat-
ter, Oxides of Sulfur, and Sulfuric Acid". J. Air Pollution
Control Assoc. 19, 639 (1969).
4. Widdicombe, J, G.: "Respiratory Reflexes from the Trachea
and Bronchi of the Cat". J. Physiol. 12 3, 55 (1954).
5. Widdicombe, J. G.: "Receptors in the Trachea and Bronchi
of the Cat". J. Physiol. 123, 71 (1954) .
6. Widdicombe, J. G., Kent, D. C. and Nadel, J. A.: "Mechanism
of Bronchoconstriction during Inhalation of Dust". J. Appl.
Physiol. 17, 613 (1962).
7. Nadel, -J. A., Salem, H., Tamplin, B. and Yokiwa, Y.: "Me-
chanism of Bronchoconstriction". Arch. Environ. Health 10,
175 (1965).
8. Nadel, J. A., Corn, M., Zwi, S., Flesch, J. and Graf, P.:
"Location and Mechanism of Airway Constriction after Inhal-
ation of Histamine Aerosol and Inorganic Sulfate Aerosol".
In Inhaled Particles and Vapors, II, Davies, C. N., Editor,
Pergamon Press, New York, 1966. p. 55.
9. West, P. W. and Gaeke, G. C.: "Fixation of Sulfur Dioxide
as Disulfitomercurate (II) and Subsequent Colorimetric
Estimation". Anal. Chem. 12, 1816 (1956).
10. Pate, J. B. , Ammons, B. E., Swanson, G. A. and Lodge, J. P.:
"Nitrite Interference in Spectrophotometric Determination of
Atmospheric Sulfur Dioxide. Anal. Chem. 37, 942 (1965).
11. Tentative Method of Analysis for Sulfur Dioxide Content of
the Atmosphere (Colorimetric). Intersociety Committee
Methods for An'.bient Air Sampling and Analysis. Health Labor-
atory Science 6. 228 (October 1969).
-------
43
12. Staub, N. C. and Storey, W. F.: "Relation Between Morpho-
logical and Physiological Events in Lung Studied by Rapid
Freezing". J. Appl. Physiol. 11_, 381 (1962).
13. Mead, J. and Whittenberger, J. L.: "Physical Properties
of Human Lungs Measured During Spontaneous Respiration".
J. Appl. Physiol, jj, 779 (1953).
14. Nadel, J. A.: "Mechanisms of Airway Response to Inhaled
Substances". Arch. Environ. Health 16, 171 (1968).
15. Storey, N. C. and Staub, W. F.: "Ventilation of Terminal
Air Units". T. Appl. Physiol. 17, 391 (1962).
16. Frank, N. R., Amdur, M. 0., Worchester, J. and Whitten-
berger, J. L.: "Effects of Acute Controlled Exposure to
SO2 on Respiratory Mechanics in Healthy Male Adults". J.
Appl. Physiol. 17, 252 (1962).
17. Balchum, 0. J.f Dybicki, J. and Meneely, G. R.r "Pulmonary
Resistance and Compliance with Concurrent Radioactive Sul-
fur Distribution in Dogs Breathing s35o0". j. Appl. Phy-
siol. 15, 62 (I960).
18. Amdur, M. 0.: "Respiratory Absorption Data and SO2 Dose-
Response Curves". Arch. Environ. Health 12, 729 (1966).
19. Daihamn, T. and Strandberg, L.: "Acute Effects of Sulfur
Dioxide on Rate of Ciliary Beat in Trachea of Rabbit in
vivo and in vitro, with Studies on Absorptiorial.Capacity
of Nasal Cavity". Int. J. Air Water Poll. £, 154 (1961).
20. Strandberg, L. G.: "SO2 Absorption in the Respiratory
Tract". Arch. Environ. Health 9, 160 (1964) .
21. Speizer, F. E; and Frank, N. R.: "The Uptake and Release
of SO2 by the Human Nose". Arch. Environ. Health 12, 725
(1966).
22. Nadel, J. A. and Widdicombe, J. G.: "Reflex Effects of
Upper Airway Irritation oh Total Lung Resistance and
Blood Pressure". J. Appl. Physiol. 17, 861 (1962).
23. Macklera, P. T. and Mead, J.: "Resistance of Central and
Peripheral Airways Measured by a Retrograde Catheter".
J. Appl. Physiol. 22, 395 (1967).
-------
44
ACKNOWLEDGEMENTS
We gratefully acknowledge the assistance of the following:
Messrs. Robert Jones and Frank Willis fabricated many parts of
the apparatus described in the report. Dr. John Frohliger was
instrumental in guiding the chemical aspects of the study. Dr.
Gene Bingham, University of Pittsburgh Veterinarian, demonstrated
and helped us to perfect the endotracheal tube methodology.
-------
45
APPENDICES
A. Reprint of "Response of Healthy Men to Inhaled Low Concen-
trations of Gas-Aerosol Mixtures" by Burton, G. G., Corn,
M., Gee, J. B. L., Vasallo, C., and Thomas, A. P. AMA
Arch, Env. Hlth. 18, 681 (1969).
B. Tabular and Graphical Records of Individual Experiments.
-------
^-681
Response of Healthy Men to
Inhaled Low Concentrations
of Gas-Aerosol Mixtures
George r. BnrlmS. MJ): Afnrfon Corn. P/Jl;
-/. Berncnd L,die: Chartes^Vc^rrlio,
tind ArnurndP. Thnnuis, ft A. PiH>'"irf!h '
E
Siibntillvil Cot putilw'Hlii'.n Ann i'<, i!W, unruled
Oct 55.
From flio Graduate Sehor-I < r I'uMic Henlfli nnd
School or Medicine, University of Pittsburgh, Pa.
Dr. Burton in now at tho ljOnm J.iintu tluiverfity
School of Medicine; I-nnvi l.imln. Cnlif.
Read before the ninth AMA Aiv -Pollution Mertiriil
ItesearCh Conltrctirc, Ttenwr, ,)ulv H4,
Repriflt requesls lo rXiiartmwit of Mr-rlii'inc. See-
(ion on Medical Chest VJiscnses, I^tnia Undo IFnl-
Vtrstly"School f irtlinkd pollutants
in liunipns anrl cxfH'rinifnlal animals hav«
nrontly .been reviewed' Tliosf studies had
foiled to demonstrate changes in iung liir-
chfnics of I ton I thy adults exposed to single
pollutants at concentrations representative!
of thoso in ambient, urban air. LaBcllc ot at2
nnd later Gootz:: had suggested that gas-
aerosnl synergism might explain the hypothe-
sised adverse; effeet cm health, and (lie animal
^Indies vl Amclur < f a!, ;- (j.-ivc the weight nf
. mneiilrrablii soinul experimental dntu to l.lie
conw'tii.
Several studies have been done, lo dale, lo
determine the prowntx.' or absence of ^ar;
.¦ier'>.L,<>I synor^'iVm in man, and Ihc results arc
conflicting. Fr«r?k ft ai'J tisintf mixtures
wliirli consisted of SO. anrl a snbniicmn
Nal.'l aerosol, could demount rale no syner-
gistic effect in healthy adults over li e ra»t,re
"f'l l<» 1.7 ppm Alxij Jit) .^ipnifiraiit
ehanjws iri ptilmomry flow resistance '.1m.'1
ofciirrwl din ing exposure fo 1 to 2 ppiu SOj
witli or without the added aerosol.
Later. Toy/iir>aT studiod the effects n!" a
wide raiiRo of concentrations of SO.: alone
and in comhinntion with a monodisperse
submicroriic aerosol nf NaCI' i concentra-
tion, 7.1 m'ff/cu m). He concluded that a
synergistic re^joriw producing increased air-
way resistance wns present, oven at low
mitc-enl nit ions of . thuir^Ti fjic number nf
.I'flf Km ii'Ht n.olth—I itl JS. Apt it (Miif?
-------
/2-682 GAS-AEROSOL MIXTURES—BURTON ET AL
Tab!e 1.—Exposure Concentrations of SO. and NaC1 Aerosol'
Experimental Subjects
Mean —
Pollutants
6
7
e
10 9
1 2
3
5
4
Subjects
1.9
3.0
2.4
3.2 . 2.1
2.2 1.4
1.2
1.9
1.9
1
SO; (10 ft)
i o.oc
¦' 0.08
+ 0.15
0.13 ± 0.00
±0.00 0.14
• 0.05
- 0.S6
t 0.00
¦ 0. iq
1.9
3.1
2.8
3.G 1.9
2.1 1..?
1.2
1.8
1.7
.*. 1
SO; (20 It)
+ 0.13
¦! 0.1 1
; 0.28
±0.00 ¦•¦0.06
±0.03 ±0.03
' 0.08
¦ i).::.?
» 0.04
i 0.1
Aerosol-Mix
1.9
3.0
2.3
3.0 1.9
2.3 1.4
1.2
1.4
1.1
,'.0
(10 It)
- 0.09
• 0.00
i 0.10
-O.OO :0. 18
±0.10 r 0.02
' 0.02
i 0.07
- 0. 14
' 0.22
Aerosol-Mix
1.9
3.0
2.4
3.3 1.7
1.9 1.2
1.1
i.3
\.H
:?.o
(20 It)
• OX..!
± 0.00
i 0.22
0. IS -t 0.1 1
±0.03 '0.12
x 0.08
' 0.2 Li
'¦ 0.08
' ().??
1 NaCt|
2.4
2.0
2.0
r.7 2.1
2.5 2.3
2.1
?.o
2.2
mg /
m|'./
my/ mg/
mg/ ing/
mg/
"'tV
">>;/
• 0.08
:¦
cw m
cu m
cu in
cu m cu m
cu rn cu m
cai m
cu m
Cu in
* SO2, parts per million; NaCI. mj'j/cu in. Values are mean + ] SE.
subjects exposed to < 5.0 ppni SOL. and aero-
sol was small.
At the sixth annual Air Pollution Medical
Research Conference in 1963, Toyama8
presented studies of eight healthy young
men whom he exposed to SO... concentra-
tions (3 to 40 ppm) with and without inhala-
tions of Kawasaki industrial men dusts
(concentration, 10 to 50 mg/cu ml. Again,
he concluded that a synergistic response
could be demonstrated, though them were
"fairly wide individual differences."
Wo decided to extend these Undies W
mean11 ring airway resistance 'R j—a mure
oasily performed tent of irritant response—-
and R,„ during precisely controlled anil
eharucterizcil pollutant exposures. Further-
more,. our studies were designed to detect
possible changc9 following pollutant expo-
sure at concentrations which resembled
those found in urban air.
Materials and Methods
Subject Exposure Procedure nnd Pulmonary
Mechanics Measurement.—Studies wero per-
formed using ten healthy men volunteers rang-
ing in ago from 25 to 34 years as subjects. All
subjects had no previous hisloTy of, or physical
findings suggesting significant cardiopulmonary
disease. Five were cigarette smokers; five were
not.
Pulmonary flow resistance (R,) was mea-
sured with an esophageal balloon and a low
resistance spirometer using the technique of
Mead and Wliittenborger.0 Recordings of flow,
volume, and esophageal (intrapleural) pressure
were made on a multichanel galvanometric re-
eorder. Airway resistance (RJ was measured
using the body plethysmograph airway-inter-
ruption technique of 'lie same authors.1" Tho-
racic pas volume (TGV) was determined hy a
technique modified after Dubois et al11: Appa-
ratus resistance across the R,, Ch apparatus
was 0.38 cm H.,0 at 1 liter/sec; across the
tubing of the plethysmograph it was 0.51 cm
H.,0 at 1 liter/sec. Since Widdicombo and
Nadel1- had suggested that work of breathing
should increase with increasing respiratory fre-
quency (f) and airflow velocities, particularly if
total airways dead space (Vn) is increased, we
measured compliance (C,,) and R, during nor-
mal resting and forced ventilation at airflows
which did not exceed 2.5 liters/sec.
The subjects wore nose clips nnd mouth-
breathed, warmed, humidified filtered medical-
t'.rade air from the dilution hoard schematically
described below. Air breathing measurements
were made aftor five minutes, lir.it on Hie low
resistance) spirometer and then in Ilie body
plethysmograph. Measurements of lung resist-
ance nnd compliance wen: complete within one
minute following exposure the pletliysniof.r.-iph
data wero obtained within the following two
minutes. We felt that earlier measurements of
these parameters were unnecessary, and did
not attempt to make the exposures in the
plethysmograph itself. Subject comfort during
the hour-long total exposure was a factor in our
decision to proceed in this fashion.
Aft er control measurements were made, (lie
subject was then exposed to SO., or an SO„-
sodium chloride aerosol mixture. The order of
exposure to gas or gas-aerosol mixture was
randomized. The exposures lasted 30 minutes
each, with measurements being made at 10
minutes nnd 30 minutes. Sufficient time was
allowed between exposures to allow airway and
total lung resistance to return to control levels,
if any change had occurred. Of 19 studios
performed, ten successfully fulfilled the com-
plete criteria of rhc experimental protocol.
Pollutant Aerosol nnd Gas Generation nnd
Characterization.—Pollutant; mixtures for Ihe
Art I: Environ Ilrnlfli—Vnl 1ft. A mil
-------
Meitl Air
(Control Pariod)
Flo 1.—Schematic of pollutant generation apparatus. A, Valve; B, "catch-all" air cleaner; C, silica gel;
D, wetting tube, E, Mllllport HA filters; f, critical orifice; G, pressure geoe, H, SO, Inlet, I, mixing
balloon; J, hutlng coll with rheostat control, K, Herschel-Type Vent, In Tube, I, Dautreband D»,l, M,
motor drlvan ayrlnge; N, medical grade compressed air; triangle, flow direction.
Fig 2.—Cumulative particle—size distribution curve for test aerosols (NaCI), sized et 32,000 x with
Zeis* TQrs electron microscope.
5 100
M
040
0<05 aio 0.15 0.20 0.2S 0.30
PARTICLE PR0JECTE0 ARIA DIAMETER.
-------
-684
GAS-AEROSOL MIXTURES—BURTON ET AL
exposures were produced using a portable aero-
sol-gas 9upp]y apparatus' designed and con-
structed for this study (Fig 1).
Medical-grade compressed air was passed
tlirough activated carbon and silica gell, mois-
tened and warmed, then metered by the use of
calibrated orifices, before entering the Dautrc-
hando D3nl generator or the Vcnturi tube for
mixing with nerosol and gas. Sulfur dioxide gas
was supplied to the Venturi throat by a syringe
driven by an infusion pump. The Dautrebande
D.,„l aerosol generator wns filled with 0.225%
by weight solution of NaCl and placed in an
opening at the base of the Venturi tube. The
salt solution was replaced every 15 minutes to
prevent a significant increase in NaCl concen-
tration due to the evaporation of water.
The mixture exited from the Venturi mixing
tube into a reservoir balloon, where it was
either exhausted, or withdrawn by the subject
under test.
All components of the system, with the ex-
ception of the balloon were of stainless steel,
rigid plastic, or Teflon. The aerosol mixture
was delivered to the subject through a 1-inch
stainless steel Teflon-lined tube. At the end of
the tube was a throe-way valve. One port wa9
connected to the "control" air source; the other
port was attached to a two-way "J" valve. An
exhaust line was connected to the outlet side of
the "J" valve. A moulded contour rubber
mouthpiece which fitted inside the mouth of
tho subject was used. Caro was taken during
the exposures (o keep snliva from collecting
inside of the ".I" valve.
Measurement of pollutant concentration (lur-
ing exposures worn nindo through a stainless
steel tap which wan injected into the inspirato-
ry side of tho breathing valve ns close to the
mouth as possible.
Tn order to detcimine SO^, concentration, 2.R
liters/min of the pollutant mixture was drawn
for two minutes into a midget impinger con-
taining 50 ml of West-Gneke reagent. The sam-
ples were then analyzed spectrophotometricnlly
using (he modified West-fineke method.'-1
During the first ten-minute exposure, two
samples were taken, four minutes apart. During
the 20-minute cxposurc three samples were
taken at six-minute intervals. Whenever Rodhim
chloride aerosol wns present in tho system,
sampling was performed by first drawing a
sample through HA Millipore filter paper to
eliminate sodium chloride interferences. Sever-
al nonexposure calibration runs indicated that
tho' losa of sulfur dioxide on the filter paper
was negligible.
The concentration of sodium chloride aerosol
wns determined !>v withdrawing the exposure
mixture at 21 liters/min for 20 minutes through
HA Millipore paper, leaching the salt by filter
immersion in distilled water, and analyzing by
electrical conductivity. A calibration curve wns
prepared using reagent-grade sodium chloride.
Because of the length of timo required to
sample for the sodium chloride aerosol, this wns
done at the end of the exposure periods. Sever-
al nonexposure checks and postexposure checks
found the concentrations to bo very consistent
over a period of several hours, ie, 2.2 ± O.OS
mg/cu m (mean ± SD).
The particle size distribution of the nerosol
was determined by first sampling with an oscil-
lating thermal precipitator onto a carbon-coat -
ed glass coverslip- Tho carbon film wns trans-
ferred to n 200-mesh electron microscope grid
prior to obtaining photographs with an electron
microscope. The particles were sized using a
particle sizing unit. The particles were all
smaller than 0.40/1 hy weight, the mean size and
standard deviation were 0.25/t and ±0.001/'.
respectively (Fig 2).
Table 1 is a summary of pollutant concentra-
tions to which subjects were exposed in this
study. Variations are due to operating charac-
teristics of the generation apparatus. As experi-
ence with the unit increased, outward leaks,
and other problems were eliminated and re-
producibility of concentrations improved. These
mixtures of aerosol and gaseous pollutant were
generated to specifically simulate the urban
milieu. The concentrations of SO* nre slightly
higher than those ever recorded in nn acute nir
pollution episode (London, 1952). During that
catastrophe, the concentration of particulate
matter was 0.0 mg/cu ill.
Results
The data (Table 2) shown represent the
mean of six determinations of R, and T(!V
in tlie body plethysmograph. Other parame-
ters of pulmonary mechanics arc derived.
Pulmonary flow resistance data is presenled
as an average of inspiratory and opiratuy
flow resistances based on six 1o ten breaths.
Wlien compared with individual or mean
group controls, no significant increases in
and R,_ worn seen during quiet breathing
or during hyperventilation, either after SO.,
alone, or after the SOo-aerosol mixture. Sim-
ilarly, no significant changes in RA, airway
conductance (GA), or specific conductance
could be demonstrated. Thoracic gas vol-
ume did not change significantly. These
studies confirm those of Frank rt n!.H Men -
Arrh Ennirnn Ilonllli—Vol IS. April 7.W.9
-------
Table 2.—Effect of Exposures on Various Pulmonary Mechanics Measurements*
Control
p 10 It SOj
p 30 ft SO:
Control
p 10 ft Mix
p 30 ft Mix
Order
Individual data
Subject 6
Rl
0.41/1.23
0.91, 1.40
0.90. 1.23
1.63, 1.80
1.56. 1.90
1.30. 1.87
Cl
0.20. 0.21
0.28. 0,22
0.27. 0.25
0.27, 0.20
0.18. 0.18
0.22. O.lfl
Ra
0.70 -
0.97 —
0.95 -
1.00 -
0.96 -
0.95 -
Gas. Mi*
Ga
1.42 —
1.03 -
1.05 —
1.00 -
1.04 -
1.05 -
TGV
3.36 -
3.37 -
3.50 —
3.40 _
3.24 _
3.28 -
. Ga/tgv
0.42 —
0:31 -
0.30 -
0.29 -
0.32 -
0.32 -
Subject 7
Rl
2.02, 1.69
1.90, 1.80
1.33; 1.66
1.50 -
2.00, 1.90
1.80, 1.60
Cl
0.25, 0.21
0.29, 0.26
0.27, 0.24
0.24 -
0.28. 0.30
0.35,0.23
Ra .
1.12 - .
1.16 -
1.03 -
1.10 -
0.98 -
1.08 -
Ga
0.89 -
0.85 -
0.97 -
0.91 -
' 1.02 -
0.93 -
Gas. Mix
TGV
5.20 -
4.94 —
5.12 -
5.10 -
5.27 -
5.05 -
Ga/tgv
0.17 -
. 0.1 7 -
0.19 -
0.18 -
0.19 -
0.18 -
Subject 8
Rl
1.70. 2.30
_ _ ¦
1.05, 2.50
2.02 -
1.90. 2.30
2.00. 2.40
Cl
0.21. 0.19
— —
0.18, 0.13
0.20 -
0.16. 0.18
0.16, 0.15
Ra
1.04 -
1.11 -
1.25 -
1.02 -
1.23 -
1.13 -
Ga
0.96 -
0.90 -
0.80 —
0.98 —
0.81 —
0.88 —
Gas. Mix
TGV
2.88 -
2.94 -
2.94 -
2.99 -
2.83 -
2:97 —
Ga/TGV
0.33 —
0.31 -
0.27 -
0.33 -
0.29 —
0.30 -
Subject 10
Rl
1.84. 2.00
2.03, <:.90
1.70, 2.00
1.80, 2.00
1.70, 2.50
1.50. 2.10
Ci.
0.24, 0.21
0.31, 0.23
0.31, 0.30
0.32, 0.22
0.29, 0.22
0.26. 0.14
Ra
1.25 -
1.40 —
1.09 -
1.15 -
1.08 -
1.12 -
Gqs, Mix
Ga
0.80
0.71 -
0.92 -
0.87 -
0.93 -
0.89 -
TGV
5.28 -
5.08 -
5.38 -
4.87 -
5.25 -
5.16 -
- Ga/TGV
0,15- - .
0.14 -
0.17 -
0.18 -
0.18 -
0.17 -
Subject 9
Pl
1.60, 3,30
2. 70, 2.80
1.40, 1.70
1.40, 1.80
1.90, 1.80
1.60, 1.50
Cl
0.27, 0.25
0.30, 0.30
0.36. 0.23
0.25, 0.31
0.27.0.32
0.30. 0.25
Ra
1.04 —
1.05 -
1.04 -
1.03 -
0.97 -
1.02 -
Gas, Mix
Ga
0.96 -
0.95 —
0.96 -
0.97 -
1.03 —
0.98 -
TGV
4.48 —
4:58 -
4.50 -
4.65 -
4.82 -
4.84 —
Ga/TGV
0.21 —
0.21 -
0.21 -
0.21 -
0.21 -
0.20 -
Subject 1
Rl
1.04, 1.25
1.20. 1.10
1.50, 1,70
1.20. 1.60
1.20. 1.70
0.96. 1.80
Cl
0.39, 0.63
0.36. 0.63
0.26, 0.23
0.28, 0.30
0.30 -
0.23. 0.25
¦Ra
0.69 -
0.74 -
0.64 -
0.66 -
0.85 -
0.70 -
Gbs, Mix
Ga
1.45 —
1.35 -
1.56 -
1.52 -
1.18 -
1.43 -
TGV.
.4.40 —
4.20 -
4:35 -
3.97 -
4.16 -
3.90 -
CWTKV
(1.3.1 —
0.32 -
0.36 -
0.3 H -
0.28 -
0.37 -
«L
1.80 —
1:GC, 1.50
1,40, 1.50
2.GO.
:mo. 1.40
1.50, l.f.0
Cl
0.25 -
0.29, 0.28
0.37, 0.42
0.36. 0.37
0.30, 0.52
0.29. 0.40
Ra
1.59 -
1.65 -
1.61 -
1.57 -
1 .f,2 -
1.55 -
Mix,' Gas
Ga
0.63 —
0.6 i -
0.62 -
0.64 -
0.G2 —
0.65 -
TGV
5.68 —
5.74 —
5.54 -
6.2G -
5.54 —
5.G4 —
Ga/TGV
0.1 1 -
0. U -
0.11 -
0.10 -
0.1 1 -
0.12 -
Subject 3
Rl
. 0.99, 2.00
1.40, 1.90
1.50, 1.90
0.83. 1.3(1
1.80, 2.10
1.30, 2.00
Cl
0.24, 0.29
0.27. 0.25
" 0.27. 0.26
0.22, 0.22
0.27, 0.23
0.28. 0.27
Ra
1.05 -
1.20 ~
1.45 -
1.32 -
1.56 -
1.42 —
Mix, Gas
Ga
0.95 -
0.83 -
0.69 -
0.76 -
0.64 -
0.70 -
TGV
3.78 -
3.68 ~
3.35 -
3.44 -
3.18 -
3.38 -
Ga/TGV
0.25 —
0.23 -
0.21 -
0.22 -
0.20 -
0.21 -
Subject 5
Rl
1.41. 1.55
1.10, 1.71
1.78, 1.71
2.36, 2.37
1.93, 1.(52
1.41, 1.55
Cl
0.27, 0.25
0.25. 0.18
0.23, 0.26
0.15. 0.14
0.18, 0.23
0.27. 0.2f>
Ra
1.42 —
1.47 -
1.42 -
1.42 —
1.47 _
1.38 —
Ga
0.70 —
0.68 -
0.70 -
0.70 -
0.68 -
0.72 —
Mix. C. ir,
TGV
4.85 —
4.55 -
4.61 -
4.73 -
4.62 -
4.85 —
Ga/TGV
0.14. —
0.15 -
0.15 -
0.15 -
0.15 —
0.15 -
Subject 4
Rl
1.97,.2.09
1.89. 2.12
1.89, 2.30
1.82, 1.61
1.47, 2.05
2.28, 2.01
Cl
0.16, 0.15
0.15, 0.13
0.16, 0.15
0.15,0.14
0.15, 0.13
0.15. 0.13
Ra
1.97 —
2.05 —
2.06 -
1.67 -
2.00 -
1.83 -
Mix, Giis
Ga
0.51 ¦-
0.49 -
0.48 -
0.60 -
0.50 -
0.55 -
TGV
2.85 -
2.76 -
.2.78 -
3.00 -
2.73 -
2.89 -
Ga/TGV
0.1 fi -
0.18 -
0.17 -
0.20 -
0.18 -
0.19 -
Arch Environ .Health—Vol IS. April 10fS!)
-------
/?- 686 GAS-AEROSOL MIXTURES—BURTON ET AL
Table 2.—Effect of Exposures on Various Pulmonary Mechanics Measurements'—(Continued)
Control p 10 ft SO2 p 30 ft SO2 Control p 10 ft Mix p 30 ft Mi\ Order
Grrimped dnta
Hi. 1.48, 1.93 1.04,1.02 1.44.1.81' 1.72, t.H<> I.I.7, I.ti-I
C|. 0.2b, 0.27 0.28.0.21) 0.27. 0.2!") 0.24. 0.:M U.:.'4, 0.:T> 0.2'/\ O..M
fi'A 1.19 — 1.28 — 1.2!) — 1.19 — 1.:'/ - 1.::.'! -
.'.Ca 0.84 — 0.88 — 0.88 - 0.90 — o.H!> — O.HH -
, TGV 4.27 — 4.18 - 4.21 — 4.24 — 4.10 - 4.P11 -
'Ga/TGV 0.23 - 0.21 - 0.21 - 0.22 - 0.21 - 0.22 -
* Rl, cm H20/liter/sec; Ci, liter per centimeter H2O; Ra. cm H?0/liter/sec; Ga. 1/Ra: 1GV. liters; .mil Ga/TGV
(specific conductance), sec 1 cm H20-'.
Sub-
ject
p 10' SO2
p 30' SO?
p 10' Mix
p 30' Mix
p 10' SO2 - 6.0
p 30' S02 - 34.2
p 10' Mix + 33.3
p 30' Mix + 20.0
surements of R, and C,,
during rapid breathing were
also unaffected by any expo-
sure.
Figures 3 to 5 illustrate
the absence of significant
change in group mean val-
ues of Rtj, C|„ or Ga per
TGV following any expo-
sure condition. The R,. and
CL' data seemed to add little
to the results, for they follow
the same trends as the more
simply obtained body ple-
thysmograph data.
The wide scatter of indi-
vidual values and the lack
of significant trend enn be
6ecn in Table 2 nnd 3, and
Fig G to 8. One or two possi-
ble "hyperreactors" can be
identified here. Control val-
ues are all within reported normal ranges for
these measurements.
Except for subject 10, who complained of
some dryness of the throat, there were no
subjective symptoms associated with any ox-
Table 3.—Effects of Exposures on Lung Resistance
and Specific Airway Conductance
% Change vs Control
Suh-
Ga/TGV* jret
+ 122.2 -26.2
+ 119.5 —28.6
— 4.7 +10.3
- 20.2 +10.3
1
p 1 (V SO;
P 30' SO;
P 1 0' Mix
P MY Mi*
Kl
+ 15.3
+ 44.?.
0.0
— PO.O
C.a/TGV
- 3.0
+ 9 0
-26.3
— 2.7
0.0
+ 1 1.7
+ 9.5
0.0
10
p 10' S02 —
p 30' SO? - 38.2
p 10' Mix - 5.9
p 30' Mix — 1.0
p 10' SO? +
p 30' SO? —
p 10' Mix —
p 30' Mix —
- 6.0
- 8.2
-12.1
- 9.0
p 10' SO2 + 68.8
p 30' SO2 - 12.5
p 10' Mix + 35.7
p 30' Mix + 14.3
10.3 - 0.7
7.6 +13.3
5.6 0.0
16.7 - :>.!i
0.0
0.0
0 0
— 4.8
P 1 0' SO?
p 30' SO:-
p 10' Mix
p 30' Mix
p 10' SO;
p 30' SO;
p ! 0' MK
P 30' Mix
P 10' so-
P 30' SO-
P 10' MW
P 30'
p in' st»/
p 30' \f><
y»' in' Mi-
7) 30' Mm
- 1 I .1
_ o? ¦">
0.0
0.
- 19.2 +10.0
— 42.3 +?0.0
1 H?0
— I KO
— V.l
4.5
4 1.4
+ M-r> -
| 1 10.9 -
-¦~"V::.o 4
-i- en.:- +
\n.?.
•in..?
'i.i
4.1 -
l't. ;¦
; 1
7. I
O o
0 o
1 I.I' >
* Rl. cm HjO/liter/sec; Ga/TGV.
cmi ) l;'0 »,
posurc.
Comment
This study confirms existing evi-
d(.'ncc'",4',n that human exposures to low
concentrations (< 3.0 ppm) of SO.j in air do
not. result in immediate physiologic effects
on measures of pulmonary mechanics. Wide
subject variability, and hour-to-hour varia-
tion in airway resistance and conductance10
made detection and interpretation of small
transient change? difficult. Furthermore,
time-series analysis studies in New York17
and Tennessee18 have demonstrated a 1 to 2
day lag between peak ambient levels of SO._.
and development of cough or worsening of
asthma. Spicer1'1 has confirmed lliis relation-
ship in Baltimore, iisinjr a sophisticated
statistical analysis <>f changing SO.j con
central ions and measurements of pulmonary
airway conductance and resistance as a
function of lime !a so-called jwwer sjierlnini
analysis). Such work suggests Hint lite cx
peeled effects of low concentration ex
posurcs an1 delayed unless pulmonary
-------
GAS-AEROSOL MIXTURES—BURTON ET AL
/]- 687
'AH X
10,*10'
IOi* SO
MIX -10'
Mix-ao'
C'COMTROi
Fig 3;—Total lung, resistance (RiJ changes after exposure (grouped data).
Fig 4.—Lung compliance (CL) changes after exposure (grouped data).
0.4
Slow*
FAST X
C SOi'lO*
C tCONTBOl
(0.-W
MIX-.IO
MIX-W
Arch Environ Health—Vol 18, April IU6U
-------
688
GAS-AEROSOL MIXTURES—BURTON ET AL
C S02-I0' S02-30' C Mil 10 mi* w
C COBIICN
Fig 5.—Specific airway conductance changes after exposure (grouped data).
the aerosols in themselves need to be "irri-
tant" to produco an effect in mnn, though
tliey need not be in animals. Toyama's in-
dn.st.rinl dusts mny havo been more irritant
than the N;i('l nerosol of Frank et al" and
our own, and this may account in part for
the evocation of response from his SOn-dust.
exposed subjects.
We were able to identify nt least one
possible "hyperreactor" to S02 in the pres-
ent study (subject 3, a 24-year-old nonsmok-
er). Our work suggests, as have other
studies,1415 that there may be only one or
two physiologic "vendors" for every ten ex-
posed subjects. Tin: implication for future
exposure studies is that large numbers of
"normal" subjects will need to be studied to
locate persons who show effects of inhaled
pollutants on pulmonary mechanics.
A study which probed immediate gas
aerosol synergism in patients already affected
by pulmonary disease might report positive
results where ours havo been negative. Sup-
port for this exists in the literature,21 though
complete aerosol characterization data ;tre
not given. Medicolegal and ethical consider-
ations make studies of this kind difficult.
Conclusions
In summary, like Frank et al" and the
work recently reported by Snell and T,uch-
singer,23 we could not demonstrate gas-aero-
sol synergism for SO., and inert aerosols :it,
concentrations which approximate those in
urban atmospheres. These experiments sug-
gest that grouped population data may not
he as sensitive an indicator of effect in the
experimental exposure situation as they are
in (tie epidemiological selling. These findings
in humans arc in marked contrast to the
study in animals of Amdur et al.1 where
grouped data, as well as single responses,
gave evidence of a synergistic effect whin
guinea pigs were exposed to mixtures of
aerosol and gas similar io those reported
here. (She used tbe same indicator of re-
sponse, namely pulmonary flow resistance,
in her studies as we duO
While gas-aerosol synergism may yet be.
proven an important toxicologic mechanism
in man, we suspect that reactor, characteris-
tics of readmit, and timing and sensitivity
of measurement will have lo he more care-
fully considered in future; studies if such an
effect is to be demonstrated.
-------
GAS-AEROSOL MIXTURES—BURTON FT AT.
3.0.
2.0—
l.2_
0.8_
— O-
0.6—
0.4
5. -O-
0.2_
$0,-10'
c
c
MIX-30'
MIX -10'
6:—-Plot of lung resistance changes In Individual subjects after exposure to SO, gas and NaCl aerosol.
3.0
2.6.
2.0.
1.0_
0 B_
0.6-
0.4.
0.2
SO,- lO'
C
c
Arch Eiwiron Ih-nllh—Vol IS. April IPG:9
-------
GAS-AF.ROSOL MIXTURES—BURTON F.T AL
0.6—
-X>—
o
0.4.
0.3.
O
r»
r
E
O .
—-o
0.2.
_-cr"
u
•o-
-o-
SO," 10'
c
MIX -30'
C
MIX ¦ 10
Fiij 7.—Plnl nf li'ng compllanco cli.iinies In individual sublets alter oxposuro to SO., gns nml NciCl Hurosol.
0.6
0.5
0 0.4—
r
E
V
$ 0.3
>
0
4.
0
_«•i . .
)-@>l 1—<.
o.i_
c
MIX ¦ lo'
SO,¦30
r.
-------
GAS-AEROSOL MIXTURES—BURTON ET AL
^691
06—
0.3
0.4
O
«*
X
E
w
0 3
C SO, IO' SO, 10' C MIX • lO" MIX 30'
Fig 8.—Plot of specific airway conductance in individual tubject* after exposure to S0a gas and NaCI aerosol.
06 _
6. — "W——-
8.=fag*=f
0 5_
0.3.
O
£
E
V
0.1,
u
0.l_
SO, to"
MIX ¦ lO'
c
c
Arch Enviran llrutlk—Vol 18, April 106U
-------
-692
GAS-AEROSOL MIXTURES—BURTON ET AL
Resting pulmonary mechanics studies
may not represent the best approach to
problems of acute-effect air pollution toxi-
cology in man. Studies of distribution of
ventilation or changes in pulmonary me-
chanics following exposure during exercise
may possibly be more sensitive indicators of
response.
This study was supported by Public Hcullh Scivire
grant PH86-67-73 from the National Center for Air
Pollution.
References
1. Com, M., and Burton, G.: The Irritant Poten-
tial ol Pollutants Id the Atmosphere, Arch Environ
Health 14:54-61 (Jan) 1967.
2. LoBelle, C.W.; Long, J.E.; and Christofano,
E E.: Synergistic Effects of Aerosols, Arch Industr
Health lli297-304 (April! 1955.
3. Goetz, A.: On the Nature of the Synergistic
Action of Aerosols, Int J Air Water Pollut 4:168-
184 (Sept) 1961.
4. Amdur, M.O.: The Influence of Aerosols Upon
the Respiratory Response of Guinea Pigs to Sulphur
Dioxide, Industr Hyg Assoc Quart 18:149-155
1057.
6. Amdur, M.O.. The Physiological Response of
Guinea Pigs to Atmospheric Pollutants, hit J Air
Pollut 1:170-183 (March) 1959.
6. Frank, N.R.; Amdur, M.O.; and Whittenberger,
J.L.: A Comparison of the Acuta Effects of SO,
Administered Alone or in Combination With N.\C1
Particles on the Respiratory Mechanics of Healthy
Adults. Air Water Pollut 8:125-133 (Feb) 1BC4.
7. Toyama, T.: Studios on Aerosols: I. Synergis-
tic Response of Pulmonary Airway. Rcaistnnco on
Tnhnling Sodium Chloride and SO, in Man, Jap J
Industr Mad 4:18-27, 1602.
8. Toyama, T.: Air Pollution and IU Health
Effect* in Japan, Aruh Environ Health 8i1f>!1-173
(Jan) 1904.
0. Mood, J., and Whittenbcigcr, J.L.: Physical
Properties of Human Lungs Measured During Spon-
taneous Respiration, J Appl Physiol 6:779-796
(June) 1953.
10. Mead, J., and Whittenberger, J.L.: Evaluation
of Airway Interruption Technique as a Method for
Measuring Pulmonary Airflow Resistance, J Appl
Physiol 6:408-416 (Jan) 1954.
11. Dubois, A.B., et a!: A Rapid Plethy6omo-
graphic Method for Measuring Thoracic Gas Vol-
ume: A Comparison With a Nitrogen Washout
Method for Measuring .runrtionnl Residual Capaci-
ty in Normnl Sul:j-cts: J Clin In vest 35:32 s,
(Merch) 1966.
12. Widdicombe, J.O , anil Nmlcl, J.A.; Ainvny
Volume, Airway Resistance, and Work :ind Force of
Breathing: Theory, J Appl Physiol 18:863-803
(Sept) 1963.
13. West, P.W., nnd Gneke, G.C.: Fixation of
Sulfur Dioxide as Disulfitomcicmatc (11) nnd .Sub-
sequent Colorimetric Estimation, Anal Cham
12:1816-1819 (Dec) 195G.
14. Frank, N.R., et ol: Effects of Acute Controlled
Exposure to SOj on Respiratory Mechanics in
Healthy Male Adults, J Appl Physiol 17:252-258
(March) 1962.
15. Lawlhcr, P.J.: Effects of Inhalation of Sul-
phur Dioxide on Respiration and I'lilso Rate in
Normal Subjects, Lancet 2:745-748 (Oct 8) 1955.
36. Spicer, W.S.: Air Pollution and Mi't<*nroloi;ic
Factors, Arch Environ Health 14:18!t-IKH Man)
19G7.
17. McCanoll, J., et al: Healthy nnd the Urban
Environment: V. Air Pollution nnd Illness in 11
Normal Urban Population, Arch Eni'iron Health
14:178-1R3 (Jan) 1967.
18. Zeidborg, L.D.; Prindlc, H.A.; rind Landau,
K.: The Nashville Air Pollution Study: t. Sulphur
Dioxido «nd Bronchial Anthmft, A Pnliminnry lie-
port, Amer lieu tlcftp Din 84:480 MNI (Oct) lillil.
19. Stokingcr, H.: Toxirologiml Interactions of
Mixtures of Air l'olliitiinls, Int J Air Pollut
326 (June) 1060.
20. Anderson, D.O.: The Effects of Air ('.ontaini-
nntion on Health: II. A Review, Cancid hied /Issoc
,1 97:586-593 (Sept) 1967.
21. Lovejoy, F.W., Jr., et al: Measurement of Gas
Trapped in the Lungs During Acute Changes in
Airway Resistance in Normal Subjects ajid in Pa-
tients With Chronic Pulmonary Disease, Amcr J
Med 30:884-892 (June) 1961.
22. Snell, R.E., and T.uehsin^or, P.C.: Effects of
Sulfur Dioxide on Expira'.jry Fiow Rates and To"'il
Respiratory Renistnnec in Normal Iliunrn J-'ubjo-ts.
Arch Environ Health 18:690(1!'8 (April) lSVii).
-------
TABLE s
Cat No. '676
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VAU)ES*
Pulmonary Flow Rati stance
Mech. %
Control Stim. Change
Low %
Control SOj Change
Mech. % ¦
Control Stim.. Change
S02 & %
Control NaC1 Change
Mech. %
Control Stim. Change
9.5 68.2 617.9
°.5
Meant 9.5 6*.2
S.D. 0
REFLEX IMTACT .
S.i+ 9.5 0
9.5 "lC;f 11.6
9.5 12.9 35.B
9.1 11.0
0.6 1.7
L M.S.
9.5 59.7 528.**
9.5 59.7
REFLEX INTACT
Ht.O 15.2 60
10.6 16.3 7J.6
9.5 »5.2 60
11. It 15.6
2.3 0.6
A N. S.
10.6 72.8- 586.8 '
10.6 72.8
REFLEX INTACT
Lung Compliance
Mech. %
Control Stim. Change
Low
Control SO2 Change
Mech. % ¦
Control Stim. Change
SO, & %
Control NaCl Change
Mech.
Control Stim. Change
1^.5 3.B -73.8
Ht.5
Mean* 1U.5 3.?
S .0. 0
15.0 12.8 -13.7
15.0 12.1+ -16. U
li».5 >2.? -'3.0
1U.^ 12.7
0.3 0.2
=<0.0:
13.2 3.1| -fk.2
13.2 3-^
13.6 11.it -13.6
13.2 ll.lt -13-6
12.8 11.lt -13.6
13.2 11.If
0.4 0
P<0.05
12.1 8.3 -31.4
12,1 8.3
Sequence of ,
. Cfiallen^je '
(r, (3) <<*)¦ (5)
*Controt for.15 minutes preceding challenge.
(a) See Figure. fcN.S. = Difference between means not sigificant (P>0.05)
(b} Pulrrwnary Flow Resistance, Cm I^O/l/sec.
(c) Lung Comptiartce, ml/cm l^O.
-------
TA9LE 5 (Continued)
Cat No. 1676
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Wi
Pulmonary FJow Resistance
Control NsCl
%
Change
9.5
9.5
Mean^ 9.5
S.D. 0
12.9
14.0
12.9
'3.3
0.6
P<0.01
35.^
47.4
3*.8
Mech.
Control Stim. Change
9.5
9.5
9fl. 6
98.6
reflex ttjta;
=37.9
High
%
Control SO2 Change
9.5
10.6
9.5
12.9
9.5
12.9
9.5
12. 1
0
1.3
a .n . s
11.6
35.08
35.8
Mech. %
Control Stim. Change
9.5 96.3 808.4
9.5 86.3
REFLEX INTACT
Lung Compliance
7,
Control NaCl Change
Meet*.
High %
Control SO, Change
Mecb.
Control Stim, Change
12. 4
12. 1
Meant 12.3
S.D. 0.2
11.4
11.1
11. 4
11.3
0.2
?< 0.05
-6.9
-9.4
-6.9
1J. 7 4.1
11.7 4.1
-62
11.4 16.2 42.1
11.4 16.2 42.1
11.4 16.2 42.1
11.4
0
16.2
0
P 0.01
16.2 4.7 -71
16.2 4.7
Sequence
Cftallen
3L
(6)
(7)
(8)
(9)
*C"ntroi for IS minutes preceding challenge,
(a) See Figure.
(fa) Pulmonary Flow Resistance, Cm H2O/I/sec.
(c) Lung Compliance, mt/cm HjO.
&N.S. - Difference between means not sigificant (P>0.05)
-------
~ 68.2
0 59.7
a 72.8
O 98.6
~ 86.3
22
20
18
o
O
N
z
E
u
16
G-o
14
o
a>
a>
C
*
o
a
c
o
E
10
u
z
c
z
- <->
bl
2
0-a
- CO
~ a-Pulmonary Flow Resistance
o—— — o - Lung Compliance
I
EXPOSURE RESPONSE PROFILE:
ANIMAL NO. 1676
o<\
NTROL
S02
(27.2 ±3.4 ppm)
EXPOSURE
~WI
(Lost
Record)
*0-0-0-0
~ CONTROL
S02
(33.3 ±4.7 ppm)
+ NaCI
(I0±0.2mg/M^
, EXPOSURE
CON
>-oo-40 ppm)
EXPOSURE
o
x.
o
o
22
20
18
16 o
eg
z
E
u
N
14 i
12
U
a.
E
5
10
20 40 60 80 100 120 140 160 180
Time, Minutes
200
220
240
260
280
-------
TABLE
Cat No. 1651
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES
7S1
Pulmonary Flow Resistance
Mech. %
Con'tro1 Stim. Change
14.5
14.5
54.4 275.2
¦lean* 14.5 54.4
5.0. 0
REFLEX INTACT
Coiit ro 1
Low
so2
%
Change
14.5 11.S -18.6
14.5 163.9 1030
14.5 13.0 -10.3
14.5 11.8 -IB.6
1*4.5 12.2
it+. 5 163.9
0
0
p0.05)
(b) Pulmonary Flow Resistance, Dp H^O/l/sec.
(c) Lung CompIicnce, ml/cm HjO.
-------
TA3LE 6 (CoTtinued)
Cat Ho. 1651
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VAUJES*
Pulmonary Flow Resistance
:/
Control NaCl Chanj-r:
MecH. ' ~i-
Control Stim. Change
High %
Control. SO2 Change .
Hech. %
Control Stim. Change
13.1 11.7 -'9.3
1U.5 11.7 -19.3
11.8 -If?. 6
Meant 13.3 11.7
S.D. 1.0 0.1
N.S.
ll.*5 151.1 1267. <*
10.3
11.1 151.1
I.T
REFLEX INTACT
1^.5 19.3 35.1
Ik.5 22.9 57-9
19.3 33.1
1U.5 20.5
0 2.1
P< 0.05
9.3 119 1179,6
9.3 119
REFLEX INTACT
Lung Compliance ^
%
Control NaCl Change
Control Stim. Change
Control SOj Change
Hech. %
Cantro1 Stim. Change
lit. 1 15.1 5.2
ft. 5 15.1 5.2
15.« 5.2
Mean± 1 if. if 15.1
S.D. 0.U 0
N.S.
15.1 3.Q .-7U.U
Ht.6
lit.9 3.3
o.t»
13.6 15-7 13.
1U.1 15.7 13.^
15.7 13.U
13.9 15.7
0. if 0
L N.S.
15.7 i». 9 -68.8
15.7 <*.9
Sequence of,
Cfial len0,05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
22
20
16
16
c
14
\2
c
10
e
6
4
0 54.4
q 163 9
~ 151.1
0 119
NO. !6
EXPOSURE
PROFILE:
ANIMAL
Pulmonary Flow Resistance
0----0 Lung Compliance
f
Uj.CTi
SOe
(30.6 ± l.5ppm)
+ No CI
(10 ± 0.2mg/m3)
SO,.
(24.2 ± 3.3 ppm)
EXPOSURE
S02
(48.4 ±6.1 ppm)
EXPOSURE
Ma CI
(I0±0.2mq/m3)
control
EXPOSURE
CONTROL
CONTROL
EXPOSURE
CONT
140 160
Time, Minutes
-------
TABLE 7
Cat No. 1612
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
Mech. %
¦rq~tro1 St.im. Change
Low %
Control SOj Change
necn. 7-.
Control Stim. Change
1 SUJT /&
Control NaCI Changs
H6Cns ¦ %
Control Stim. Change
20.9 156 SkS.k
70.fi
lean! 20..9 156
S.O. 0
REFLEX INTACT
20.9 27.1 29.7
20.9 28.1 3t».'»
20.9 30.2 kU.S
20.9 28.5
0 1.6
+0.05
28.1 103 329.2
23
20.9
2h.Q 103
3-7
REFLEX INTACT
20.9 29.2 39.7 .
20.9 25.6 22.5
27.1 29.7
20.9 27-3
0 1.8
P<0.05
20.9 ¦ 119 b69.U
20.9 119
REFLEX INTACT
Lung Compliance ^
Mech. %
Control Stim. Change
Low %
Control ;?2 Change
Mech. %
Control Stim.Change
S02 + %
Control NaCI Change
Mech. %
Control Stim. Change
6.3 5.0-21.3
6.1+
leant 6.3
S.O. O.l
'7.0 i.'S -8.5
7.i 6.6 -7.0
7.1 6. '¦* -9.9
7."
0."' D.i
P<0.01
6.9 6.9 0
7-0
6.9
6.9 6.9
0.1
7A 7.1 -1 .*»
7.0 8.£t 16.7
7.1 -1 .*~
7.2 7.5
0.3 0.6
A N.S.
7.7 7.7 0
7.7 7.7
Sequence of >
CRal 1en0.05)
(b) Po IfTK>nary Flow Resistance, Cm f^O/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE 7 (Continued)
Cat rlo. 16)2
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance ^
V,
Control NaCl Change
Mech. 5?
Control Stim. Change
High %
Control SO2 Change
Mech. %
Control Stim. Changs
20.9 38.7 85.?
20.9 30 i+3.5
33.9 62.?
Meant 20.9 3*+.2
S.O. 0 k.k
p< 0.05
20.9 SI.6 290. k
20.9 81.6
REFLEX INTACT
20.9 28.1 3k.k
20.9 27.1 29.7
23 32.2 5^.1
21.6 29.1
1.2 2.7
P< 0.05
20.9 134 54.1
20.9 13k
REFLEX INTACT
Lung Compliance
%
Control NaC' Change
Mech. ~-i
Contml S Hm. C-a~ce
High %
Control SO2 Change
Mech. %
Control Stim. Change
7.7 9.3 Q,2
7.? 9.Z+ 10.5
9.1 6.6
wean- 7.6 9. ?
S .0 . 0.1 0. ?
P<0.01
9.« 6.7 -23.°
9.9 f . 7
7.7 6. it -13.i
6.5 8.U lit. 0
7.9 6.1 -17.2
7.U 7.0
9.8 1.3
A N.S.
7.1 S.O -29.6
7.1 5.0
Sequence af » !
Cfcallen^e )
on
r-..
'Control for IS minutes preceding challenge.
(a) See Fieui-e. fiN.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/s?c.
(c) Lung Coinpi i dnce, ml/cm H^O.
-------
~ 103
Q119
~ ai.e
0134
EXPOSURE RESPONSE PROFILE
ANIMAL NO. 1612
Pulmonary Flow Resistance
0----0 Lung Compliance
S02
(32 ±0.5 ppm)
EXPOSURE
ONTROL
CONTROL
« 34
S02
(20.1 ± 2.1 ppm)
EXPOSURE .
1- A
CONTROL
CONTROL
Id l»
UJlCff
a 26
SOj
(2J.3 *0.6 ppm)
f NoCI
(10 ± 0.2 mg/M1)
EXPOSURE
NoCI
(10 ±0.2 mg/M3)
EXPOSURE
120 140 160
Tine, Minutes
-------
TABLE 8
Cat No. '633
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
(bj
Control
Mech.
S t i m.
Change
Control
Low
SO2
%
Change
Control
Mech. %
Stim. Change
Control
so2+
NaCl
%
Change
Control
Mech.
Stim.
%
Change
16.9
17.9
122
601
15.9
15.9
'5.9
\U. 0
15.6
1*4.2
-11.9
-'.9
-10.7
16,9
15.9
80.1 389.9
15-9
15.9
15.9
19-1
17-9
20.8
20. 1
12.6
30.8
17-9
19.5
82
338.5
Mean! 17.*+
S.D. 0.7
122
15.9
0
lit.6
0.9
16.1*
0.6
80.1
15.9
0
19.3
1.5
18.7
1.1
82
REFLEX INTACT
N.S .
REFLEX INTACT
A N.S.
REFLEX INTACT
Lung Compliance
Contro1
Mech.
S ti n.
%
Change
Contro1
Low
SO2
CHanqi
Control
Mech. %
Stim. Change
Control
SO2 +
NaCl
%
Change
Control
Mech.
Stim.
%
Change
3.0
7.7
3.6
-Sk. 1
7.7
7.7
7.7
7.5
7.5
7.7
-2.6
-2.6
0
8.1
7.5
8.1 3.8
7.7
7.5
7.5
7.0
7.1
7.3
-7.5
-6.2
-3.5
7.7
7-3
k.2
-kk. 0
7.9
S.D. 0.2
3.6
7.7
0
7-6
0. 1
N.S .
7.8
0.4
8. l
7.6
0.1
P<
7.1
0.2
-0.05
7.5
0.3
k.2
Sequence 0.05)
(b) Pulmonary Flow Resistance, Cm ^O/l/sec.
fc) Lung Compliance, ml/cm H^O.
-------
TA9LE v.8 (Cont inued)
Cat No. 1633
RESPONSE TO VARIOUS STIMULI EXPSESSEO AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
w
%
•Mech. %
Hi gh
%
Mechi %
Control
NaCI .
Change
Control
Stim. Change
Control SO2
Change
Control
Stim. Change
15.9
19.1
20.1
17.9
112.5 565.7
15.9 16.9
6.3
17.9
100.3 ^09.1
15.9
21
.5
35.2
15.9
15.9 n».o
-11.9
21.5
17. k
9.<*
15.9
0
Me3nJ 15.9
19.3
16.9
112.5
15.9 15.6
19.7
100.3
S.O. 0
2.1
\.k
0 1.5
2.5
N.
S.
REFLEX INTACT
A N.S.
REFLEX INTACT
Lung Compliance
%
Mech. %
High
%
Mech. '/-
Contro1
NaCI
Change
Control
Stim. Cnanoe •
Control SO2
Change
Control
Stim. Change
8.1
6.
9
-12.7
7.3
3.3 -5^.2
7.1 8.6
22
7.7
5.1* 2.3
7.7
6.
9
-12.7
7.1
7.0 7.7
9.2
7.'*
6.
9
-12.7
l.h
5
Feant 7.9
6.
9
7.2
3.3
7.0 7.9
7.6
S.k
S.O. 0.3
0
0. 1
0.1 0.6
0.2
N.
S.
L N.S!
Sequence at.
Cftal 1en0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
~ 122 0 80.t o 82.0 o 112.5 I00.3g
EXPOSURE RESPONSE PROFILE:
ANIMAL NO. 1633
26
20
o Q Pulmonary Flow Resistance
0----0 Lung Compliance
24
u
22
2-
-j
CO
o
o
z
z
u
u
CO
<0
__ A
,£>. o *> -o* \vo-00
JO
a.
so2
(20.3 *1.0 ppm)
+ NaCI
(10 ±0.2 mg/M3)
- EXP0SURE-4
S02
(21.6 ±2.3 PPM
- EXPOSURE —
NoCI
(I0±0.2mg/M3)|
~ EXPOSURE —
S02
(31.8 ± 2.3ppm
- EXPOSURE <
CONTROL-
CONTROL-
CONTROL
CONTROL
o
20
0
40
60
140
160
180
300
80
100
120
200
220
240
260
280
Time , Minutes
-------
TABLE 9
Cat No. '606
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
Mech. %
Control Stim. Change
Low %
Control SO2 Change
Mech. %
•Control Stim. Change
S0,+ %
Control Natl Change
Mech. %
Control Stim. Change
19.9 127 538
19.9
Meant iq.q 127
S .D. 0
REFLEX INTACT
19-9 15-7 -17.2
18.5 15.7 -17.2
18.5 21.9 15.5
19.0 17.8
0.8 3.6
A N.S .
18..5 87. 4 372.4
18.5 87. 4
REFLEX INTACT
17.1 16.6 0.2
1 '4, 1 16.6 0.2
18.5 '6.6 0.2
16.6 16.6
2.2 0
A N.S.
14.1 112 6.94.3
14.1 112
REFLEX INTACT
Lung Compliance
Mech. %
Control Stim. Change
Low y_
Control S0p Change
Mech. %
Control Stim. Change
S02+ %
Control NaCl Change
Mech. %
Control Stim. Change
Q. 7 6.9 -27.*+
9.3
Meant P.5 6.9
S.D. 0.3
9.1 9.1 -2.2
9.3 9.3 0.0
9.5 9.5 2.2
9.3 9.3
0.2 0.2
an.s.
9.7 4.7 -5J.5
9.7 4.7
9.9 7.6 -20.8
10.2 7.3 -24
8.7 7.5 -21.9
9.6 7.5
0.8 0.2
•P < u. 0 5
8.4 4.1 -51.2
8.4 4.1
Sequence of j
Cfial ten0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE 9 (Continued)
Cat No. 1606
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUE'
7-
Control NaCl Change
Mech. y~
¦ Control Stim. Change
High %
Co.itrol SO2 Change
Mech. %
Contro.l Stim. Change
14. 1 H.7 -31-3
18.5 11.6 -31.9
18.5 8.4 -50.7
Meant 17.0 10.6
S.D. 2.5 1.9
P<0.05
19.2 96.3 401.6
19.2 93.3
REFLEX INTACT
19-9 22.3 17-6
18.5 2 5 3 23.4
18.5 19.9 4.9
19.0 22.5
0.8 2.7
A N.S.
18.5 61.1 230.3
18.5 61.1
REFLEX INTACT
Pulmonary Flow Resistance
W
Lung Compliance
Control iJaCI
V.
Change
<5.1
7.6
8. 9
7.6
8.5
7.7
Meant
K. 9
7.6
S.D.
0.4
0. !
P< 0.05
-14.6
-"4.6
- i 1. 5
Sequence c|faj
Cfta 1lertge
Mech. V
Control Stim. Change
8.5 ft. I -51.i
8.3 4.
High % I Mech. %
Control S02 Change ] Control Stim. Change
6.7
1.2
7.2
7.0
0.3
8. 2
7.1
7.1
7.5
0.6
&N.S.
16.6
2.4
0.9
7.9
7.9
7.6
(M
(7)
(8)
(9)
*CnntroJ for 15 minutes preceding challenge.
(a) See Figure. 0 N.S. = Difference between means not siyificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm H2O.
-------
30
28
26
24
22
20c
18
16
(
14
12
10
C
~ 127
~ 87.4
~ 112
Q96.3
~ 61.1
CONTROL
S02
(20 i0.5 ppm)
EXPOSURE
<
u
z
_ r
u
P-Q
>3
J I L
J I ' i 1 i
EXPOSURE RESPONSE PROFILE:
ANIMAL NO. 1606
CONTROL
so2
(2l.6*0.6ppm)
+ NoCI
(10 ±0.2mg/M3)
EXPOSURE , CO
NaCI
(I0±0.2mg/M3)
NTROL , EXPOSURE
J 1 I I I ft i i
S02 O
(31.1 11.7 ppm) ^
EXPOSURE
CONTROL
«xA
\ JX>
V
20 40 60 80 100 120 140 160
TIME, MINUTES
180
200 q 220
8.4
240
260
280
30
-------
TA9LE 10
Cat No. ''12
RESPONSE TO VARIOUS STIMULI EXPRESSEO AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
Low %
Control SO2 Change
Hech. %
Control Stim. Change
S02+ %
Control NaCl Change
Mech. %
Control Stim. Change
%
Control NaCl Change
18.1 27.6 57.1
18.1 29.2 66.2
16.5 27.6 57.1
Mean! 17.6 28.1
S.D. 0.9 0.9
r-test P< 0. CI
19.7 65.7 233.5
19.7
19.7
19.7 65.7
0
REFLEX INTACT
!8.1 25-9 ^3.1
18.1 34.4 90,1
18.1 28.8 59.1
18.1 29.7
0 4.3
p< 0.05
18.9 49.8 156.2
19.7
19.7
19.4 49.8
0,5
REFLEX INTACT
18.9 14.9 -23.3
19.7 20.3 4.5
19-7 23.1 18.9
19.4 19.4
0.5 4.2
A N.S.
Lung Compliance
Low %
Control SO2 Change
Mech. %
Control Stim. Change
S02+ %
Control NaCl Change
%
Control Stim. Change
%
Control- NaCl Change
15.5 12.9 -4.2
12.8 13.2 -1.2
11.8 12.8 -4.2
Heani 13.U 12.9
S.D. 1.9 0.2
t-test A N.S.
11.5 11.5 +0.0
H.3
11.8
11.5 11.5
0.3
ll.3 12.8 13.6
11.0 14.5 28.7
11.5 12.5 10.9
11.3 13.3
0.3 1.1
A N. S.
11.5 16.0 47.7
10.5
10.5
10.8 16.0
0.6
11.5 9.2 -15.1
10.5 10.0 -7.7
10.5 9.2 -15.1
10.8 9.-5
0.6 0.5
-0.05
Sequence of } (1)
Cfcal 1en«je '
(2) (3) (4) (5)
*Cr»ntroJ for 15 mi.vjtes preceding challenge.
(a) See Figure. fcN.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
fc) Lung Compliance, ml/cm f^O.
-------
TABLE lQ (Continued)
Cat Mo. 1112
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance ^
High -/-
Control S02 Change
Mech.
Control Stim. Charge
16.5 Ul.1 1^9.1
16.5 37.3 1?*.1
16.5 Mt.9 172.1
Mean! 16.5 M . 1
S.D. 0 3.8
t-test P<0.01
20.3 37.3 82
20.3
20.9
20.5 37.3
0.3
REFLEX INTACT
Lung Compliance
High %
Control SO2 Change
%
Control Stim. Change
10.5 17.2 63.8
10.5" 15.0 l* 2.9
10.5 18.6 77.1
Meant 10.5 16.9
S.0. 0 1.8
t-test P<0.05
11.5 1^.0 29-6
11.0
10.0
10.8 li+.O
0.8
Sequence of . (6)
CRallen0.05)
(b) Pulmonary Flow Resistance, Cm HjO/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
3:65 7
:49.E
44
42
44 -
38 -
34 -
- 32
. 30
X 26
24
22
20
ie
15
— O P'_!mcno:y Ft'o* nev.sldnce
o-*--o Lung Cofroliance
EXPOSURE RESPONSE PROFh
!'•: v:: 'JO 1112
sc2
( 18 4 x O.Sppni)
EXPOSURE j
CONTQOl
S02
(19.3 ± 0.8ppm)
+ NaCI
(I0± 0.2mg/M5),
I EXPOSURE
CONTROL
NaCI
(I0± 0.2mg/Ms)
EXPOSURE
CONTROL
_L
p-o
_L
20
18
o
rvj
X
i6 e
14 =
12
10
e
340
IOC
¦20
.40
•6G 'SO
lime. M ¦ n u; e s
300
320
-------
TABLE 11
Cat Mo. '609
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
Mech.
Control Sti.n.' Change
Low %
Control SO2 Change
Mech. %
Control Stim. Change
so2+ %
Control NaCl Change
Mech.
Control Stim. Change
19-3 1"» ^3.6
20.5
18.9
Meant 19.5 11^
S.D. 0.9
REFLEX INTACT
20.1 19.3 6.6
18.1 20.3 '3-3
19.1 20.5 '3.3
19.0 20.1
1.0 0.7
A N.S.
18.1 162 795
18.1 162
REFLEX INTACT
18.1 18.1 0
18.1 20.5 13.3
17.0 15.8 -12.7
17.7 18.1
0.6 2.U
A N.S.
15.8 72.5 398.3
13.3
1^.6 72.5
1.8
REFLEX INTACT
Lung Compliance
Mech. %
Control Stim. Change
Low ~t_
Control SO2 Change
Mech. %
Control Stim. Change
so2+ %
Control NaCl Change
Mech. yz
Control Stim. Change
8.9 5.0 -Wf.9-
9.1
9.2
Meant °. ! 5.0
S.D. 0.2
9.^ 8.5 -e!.6
9.2 9.U 1.1
9.2 8.9 -«». 3
9.3 8.0
0.1 0.5
L N.S.
9.7 U.5 -53.6
9.7 h.S
9.7 9> -5.1
10.1 S.k -5.1
9-9 9-^ -5-1
9-9 91*
0.2 0
A N.S.
10.6 7.9 -2<*.k
10.3
10.5 7.9
0.2
C^nUfa) (,) t2J (3) W (5)
"^Control for 15 minutes preceding challenge,
(a) See Figure. a N.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance* Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE 11(Cont i nued)
Cat No. 1609
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance 1 '
High
Control SO2 Change
Mec h.
Control Stim. Change
17.0 !7.6 -2.8
18.1 22.8 26.0
18.1 21.7 '9.S
leanl 17.7 20.7
S.O. 0.6 2.7
t-test t> M.S.
15-8 1?2 . 7 67- 6
1$.122.7
REFLEX INTACT
Lung Compliance
High %
Control SO2 Change
Mech. %
Control Stim. Change
9.9 9.2 -7.7
9.9 Q.U -5.7
10.1 8.2 -7.7
leant 10.0 8.9
S.O. 0.1 0.6
t-test A N.S.
9-9 5.3 -W. 5
9.9 5.3
IVTS" ?•> (6>
C*81 lenqe
(7)
*ControJ fr>r 15 winutes preceding challenge,
(a) See Figure. &tl,S. = Difference between means not sigiflcant (P>0.Q5)
(b) Pulmonary Fiow Resistance, Cm
(c) Lung Compliance, ml/an HjO.
-------
~ 114
Q162
O72.0
122.70
22
18
16
14
12
10
8
EXPOSURE RESPONSE PROFILE:
ANIMAL NO. 1609
<
o
o
UJ
*o-o
Pulmonary Flow Resistance
o—--o Lung Compliance
CONTROL
S02
(20.7 ± 3.3 ppm)
EXPOSURE .
22
20
18
16
o
14
E
u
<
u
<
z
o
CO.
3
_l
3
z-
h
(0
a>
u
12.2
a.
E
o
a
o>
10 =
- 8
CONTROL
S02
(25.7 ± 2.7ppm)
+ No CI
(10 ± 0.2mg/M5)
EXPOSURE
CONTROL
—I
so2
(36.1 11.6 ppm)
EXP'OSURE
° I
z
o
a
X
JL
0
20
40
60
80
100
Time,
120
Minutes
140
160
180
200
220
-------
TABLE 12
Cat No. 1564
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance ^b'
Mech.
Contj 1 Stim. Chancio
Low i.
Control SOj Change
Mech. %
Control Stim. Change
S0,+ %
Control NaCI Change
Mech. %
Control Stim. Change
I1.1 76.3 6^5.6
9.0
9.9
¦leant 13.3 76.3
5.D. 0.7
REFLEX INTACT
<=>./ 7.1 -?9.9
9.7 8.4 -17.1
11.0 9.5 -6.2
10.1 8.3
0.8 1.2
A N.S.
8.4 121.7 '337.<~
7.1
9.9
8.5 121.7
1.4
REFLEX INTACT
11.0 9.5 8.8
7.6 8.8 0.8
7.6 8.8 0.8
8.7 9.0
2.0 0.1+
A N.S.
11.0 29.5 237.8
7.6
7.6
8.7 29.5
2.0
REFLEX INTACT
Lung Compliance
Mech. %
Control Stim. Change
Low %
Control SO2 Change
Mech. %
Contro1 Stim. Change
S02+ %
Control NaCI Change
Mech. %
Contijl Stim. Change
9.9 6.3 -36.'+
9.9
9.9
¦leant 9.9 6.3
5.0. 0
14.6 14.2 1.2
14.2 12.9 -8.1
13.3 13.2 -5.2
14.0 lj.4
0.7 0.7
L N.S.
20.1 9.9 -'~9.5
17.6
21.1
19.6 9-9
1.8
11.2 12.9 19.1
11.2 12.2 12.2
10.1 23.;'+ 116.0
10.8 16.2
0.6 6.3
£ N.S.
11.2 8.1 -25.2
11.2
10. 1
10.8
0.6
Sequence <^faj
Cftallen
S®.
(1)
(2)
(3)
CO
(5)
"^Control for 15 minutes preceding challenge.
(a) See Figure. &N.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE (Continued)
Cat No. 15&f
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Rati stance
High %
Co'i^'-ol SO; Change
P.7 7.1 -23.^
8.U 5.2 -<*3.9
9.7 S.B -37.U
4eani 9.3 6.0
>.D. 0.3 1.0
P<0.01
Lung Compliance
High ~A
Control SO; Change
19.2 16.3 7.9
10.9 13.7 -9.3
15.2 1l».6 -3.3
leant 15.1 1^.9
;.d. k.2 1.3
L N.S.
Sequence af « I f6)
Cl»a11en„eV ' |
*Contro1 for 1? minutes preceding challenge.
(a) See Figure. N.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm ^O/l/sec.
(c) Lung Compliance, ml/ctn 1^0.
-------
29.5
~ 121
q 76.8
26
EXPOSURE RESPONSE PROFILE:
ANIMAL NO. 1564
~ ~ - Pulmonary Flow Resistance
0---0 - Lung Compliance
22
24
S02
(15.9 ± l.7ppm)
EXPOSURE
20
22
ONTROL
I SOj,
j (24.3±3.0ppm)
jcONTROL EXPOSURE
V)
o
20
o
Ul
CO
16 o
o
12 -
o
S02
(17.5 ± I.Oppm)
+ Na CI
(I0±0.2mg/M3)
EXPOSURE
CONTROL
20
280
300
320
40
60
80
120
200
Time, Minutes
220
240
260
100
-------
TABLE 13
Cat No. 1593
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
(b)
Control
Mech.
Stim.
%
Change
Control
Low
S02
%
Change .
Control
Mech.
Stim.
%
Change .
Control
SO2+
NaCI
. %
Change
Control
Mech.
Stim.
%
Change
8.2
<».o
6.4
110
1298
11.1
8.8
8.8
6.4
11.2
5.8
-33.1
17-1
-r39.4
11.1
9.0-
9.8
80.1
731.5
9-0
10.1
10. 1
10.1
12.4
8.8
3.8
27.4
-9.6
10.1
82.8
719.8
Mean* 7.9
S.D. 1.3
no
9.6
1.3
7.8
3.°
9.6
'•3
.80.1
9.7
0.6
10.4
1.8
10.1
82.8
t-test reflex
INTACT .
A N.S.
REFLEX INTACT
A
N.S.
REFLEX INTACT
Lung Compliance
Control
Mech.
Stim.
%¦
Change
Contro1
Low
SO2
%
Change
Control
Mech.
Stim.
%
Chaige
Control
S02 +
NaCI
%
Change
Control
Mech.
Stim.
%
Change
10.4
10.4
19.4
6.0
-55.4
1-5.2
15.2
16.2
17.3
16.7
>7.3
11.4
7.5
11.4
17.3
19.4
19.4
4.9
-73.8
14.7
15.2
14.3
18
15.2
15.7
22.2
3.2
6.6
20.2
6.4
-68.3
Meant 13.5
S.D. 5.3
6.
0
15.5
0.6
17.1
0.3
18.7
1.2
4.9
14.7
0.5
16.3
1.5
20.2
6.4
t-test
p< 0.05
A
N.S.
Sequence of i
Challenge
(i)
(2)
(3)
(4)
(5)
^Control for 15 minutes preceding challenge.
(a) See Figure. a N.S. = Difference between means not sigiftcant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Cnmp1iancef ml/cm HjO.
-------
TA8LE 13(Continued]
Cat No. '593
RESPONSE TO VARIOUS STIMULI EXPRESSEO AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pu
lmonary Flow Resistance
Hi gh %
Contrjl SO? Change
Mech. %
Control SHm. Change
11.1 13.5 ¦ 19.8
8.9 1/4.3 23.2
15.9 1*». 7 13.1
Meant 11.9 1^.2
S.O. ?.6 0.6
t-test A U.S.
11.1 67.^ U6k.<*
8.8
15.9
11.9 67.U
3.6
reflex intact
Lung Compliance
High %
Control SO2 Change
Kech.
Control Stim. Change
19 15.2 -1if.l+
IS 15.2 -. i+
17.3 15.2 -17.3
lean! 17.8 15.2
3.D. 0.f+ 0
t-test P< 0.01
13 h. 6 -7U.1
18
17.3
17.8 k.e
Sequence of,
CfiaIlenge '
(6)
(7)
^Control for 1? minutes preceding challenge.
(a) See Figure. fcN.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance* Cm H20/l/sec.
(c) Lung CoFipIianca, rrl/cm HjO.
-------
24
22
20
u
% 18
illO
o-—-
E
u
of
o
c
o
16
.£ 14
cc
s
o
o
c
o
6
3 •
Q.
12
o—c
10
7
3 Pulmonary F
O Lung Corr;p!:<
tn
=>
-1
3
S
H
CO
<
o
u
Ui
o80.l
EXPOSURE RESPONSE PROFILE
ANIMAL NO. 1593
q28.8
q82.8
ow Resistance
©
a
¦
i
i
i
•
t
i
•
¦
A
o-gT
i
©
• \
A.
o
\ /
*o_o'
\
V
/
o
J>-©
I 10
I 3
« -1
/ H
& £
<
X
o
UJ
f
CONTROL
so2
( 22 ± 3.2ppm)'
EXPOSURE
CON
_L
_L
TROL
S02
(22.4 ± 0.7 ppm)
+ No CI
(I0± 0.2 mg/M3)
EXPOSURE .
q67.4
I
24
v>
3-
22
- 20
- 18
o
N
"I"
16 S
a.
E
o
o
12 ?>
10
8
CONTROL
_L
20 40 60 80 100 120 140 160
Time, Minutes
_L
S02
(31.4 ± 2.0 ppm)
EXPOSURE
180
200
220
_L
0
1
240
260
280
300
-------
TABLE (Continued)
Cat No. 1566
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
(b)
Control
Mech.
St i m.
%
Change
Control
Mech.
St im.
%
Change
Control
Hi gh
S0^
%
Change
Control
9.6
<9.6
4. 6
175.1
1724
10.7
9.2
15.3
201
1613
15.0
13-5
13.5
1«.5
11.3
12.2
32. 1
-19.3
-12.9
14.8
16.9
Mean! 9.6
S.D. 0
175.1
11.7
3-2
201
14.0
0.9
14..0
3.8
15.9
1.5
t-test REFLEX INTACT
REFLEX INTACT
A
N.S.
Lung Compliance
Control
Mech.
S t im.
/.
Change
Contro1
Mech.
S t i m.
%
Change
Control
Hi gh
so2
%
Change
Control
i
O CTN^J j
OO 1
<+.5
-35.7
8.5
5.5
ll.l
4.5
-46.2
8. 1
7-9
7.5
7.9
7.5
7.5
0.9
-4.3
-4.3
8.1
7.7
Meani 7.0
S.D. 0.4
4.5
8.4
2.8
4.5
7.8
0.3
7.6
0.2
7.9
0.3
t-test
Zs
N.S.
Sequence of » j
Challenge |
(6)
(7)
(8)
(9)
^Control for IS minutes preceding challenge.
(a) See Figure. & N.S. = Difference between means not sigificant (P>0.05)
(fc) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/rm h^O.
-------
TA8LE 14
Cat No. '566
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Reiistance
lb)
Control
Mech.
Stim.
¦ %
Change
Control
Mech.
Stim.
%
.Change'
Low
•Control SOj
%
Change
1
Control
Mech.
Stim.
%
Change
Control
S02+
NaC1
%
Change
11.9
13.6
1-2.1
93.
5
6U6
8.8
1C.lt
232.2
2318.8,
9.2
9.2
9.2
10.0
10.2
10.it
8.7
ib.9
13.0
11.9
8.8
112.2
98U.1
9.6
9.6
9.6
13.5
11.1
15.0
itO.6
15.6
56.3
lean! 12.5
;.D. 0.9
Q3-
5
9.6
1.1
232.2
9.2
0
10,2
0.2
-
10.
2.2
112.2
9.6
0
13.2
2.0
--test REFLEX
INTACT
REFLEX INTACT
P^0.05
REFLEX INTACT
A N.S.
Lung Compliance ^
Control
Mech.
Stim.
%
Change
Control
Mech.
Stim.
%
Change
Low
Control SO2
%
Change
Control
Mech.
St im.
%
Change
Control
S02+
NaCl
%
Change
5.9
5.9
5.9
6.6
11.9
9.1
8.3
3.3
r62.1
9.0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/era HjO.
-------
93.5b q 232 a 112 o 175 b20I
EXPOSURE RESPONSE PROFILE
ANIMAL NO. 1566
- 22
¦0 Pulmonary Flow Resistance
¦o Lung Compliance
20
V)
10
S02
(20.2 ± 1.3 ppm)
+ NaCI
(I0± 0.2mg/M3)
EXPOSURE
S02
(19.6 ±0.9 ppm)
EXPOSURE
CONTROL
COfJTRO
o
o>
10 -1
tne
S02
(2 6.0± 1.9 ppm)
EXPOSURE
CONTROL
CONTROL -
80
60
20
40
100
120
140
Time
160
Minutes
60
200
220
240
300
260
280
-------
TABLE 15
Cat No. 1113
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
"Mech. " %
Control Stim. Change
Low
Control S02 Chafije .
Mech. %
Control Stim. Change
so,+ %
Control NaCI Change
High. %
Control S02 Change
' 16. 1 233.? 13^
16.1
16.1
Meanl' 16.1 233.2
S.D. 0
REFLEX INTACT
16.1 19.2' 19.3 "
16.1 17.8 10.6
16.1 2t.6 52.8
16.1 20.5
0 3.6
A N. S.
15.2 129.3 718
16.1
16.1
15.8 129.3 "
0.5
REFLEX INTACT
16.1 10.8 -32.9
16.1 18.8 16.8
8.8 -t»5.3
16.1 12.8
0 5.3
AN.S.
16.1 21.2 31.7
16.1 19-5 31.1
16.1 17.8 10.6
16.1 19.5
0 1.7
AN.S.
Lung Compliance
Mech. %
Contro1 stim. Change
Low; %
Control S02 : Change
Mech. %
Control Stim. Change
so2+ %
Control NaCI Change
High %
Control S02 Change
12.k k.7 -60.3
12
11.1
Meani 11.8 k.7
S.D. 0.7
11.1 12.0 6.2
11.1 11.'+ 0.9
11.7 12.k 9.7
11.3 11.9
0.3 0.5
A M.S.
n.i» 5.0 -55.5
11.1
11.1
1.1.2 5.0
0.2
10.R 9.1 -20.2
12.0 10.2 -10.5
9.1 -20.2
11.^ 9.5
0.8 0.6
A N.S.
11.1 10.8 -0.9
11.1 10.8 -0.9
10.5 10.5 -3.7
10.9 10.7
0.3 0.2
A N.S.
Sequence of .
CRal lenfle O (3) (k) (5)
^Control for 15 minutes preceding challenge.
(a) See Figure. fcN.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm H20.
-------
¦ EXPOSURE RESPONSE
ANIMAL NO. 1113
PROFILE
Pulmonary Flow Resistance
g—-o - Lung Compliance
(I9.8±l.3 ppm)
+ NaCI
(I0±0.2mg/M3)
EXPOSURE
S02
(29 ±1.3 ppm)
EXPOSURE-
CONTROL
CONTROL
I6CMJ-G
SO 2
( 20.6 ±0.6 ppm)
EXPOSURE
NTROL
120
Minute
Time,
60
~ 8 8
-------
TABLE 16
Cat No. 1432
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Reiistance
(bj
Mech.
% .
Low
%
S02+
%
High
%
Control
Control
Stim.
Change
Control
S02
Change -
Control
NaCI
Change
Control
S02
Change
49.0
70'
88.7
20.<*
20.1
-11.1
24. 6
22.1
7.1
20.5
11.8
-42.7
18.4
35.^
23.9
21,6
-4.4 .
19.1
23.3
12.9
23.3
10
-51.5
11.7
26.5
23.1
19.1
-15.5
18.2
26.7
29.4
18
13.9
-32.5
Mean* 37.1
70
22.6
20.3
20.6
24.0
20.6
11.9
15.1
S.O. 11.3
1.6
1.3
3.5
2.4
2.7
2.0
4.7
REFLEX
INTACT
A N.S.
A
N.S.
P <
0.01
Lung Compliance ^
Hech.
%
Low
%
SO2 +
%
Hi gh
%
Control
Stim.
Change
Control
S02
Change
Control
NaCI
Change
Control
so2
Change
Control
<*.4 :
17.6
74.3
9.9
10.1
0.7
14.1
14.6
11.5
13.3
10.4
-11.6
8.4
9.3
9.3
11.8
17.6
11.5
14.6
11.5
10.5
8.4
-28.6
10. 1
12.5
10.9
11.2
11.6
13.7
12.9
-1.5
11.5
8.4
-28.6
»1eant10.1
17.6
10.0
11.0
13.1
14.0
1J .8
9.1
9.3
S.D. 2.2 ,
0.8
0.9
1.4
1.0
1.4
1.2
1.2
± N.S.
b N.t.
P<
0.05
Sequence qt
B)|
(1)
(2)
(3)
(4)
(5)
CRa11en0.05)
(b) Pulmonary Flow Resistance! Cm HjO/l/sec.
(c) Lung Compliance, ml/cm ^0.
-------
35.8C, 4S O Q E70
28
EXPOSURE RESPONSE PROFILE
ANIMAL NO. 1482
30
26
¦G Pulmonory Flow Resistance
•o Lung Compliance
28
24
26 -
22
24
20 E
(j
22
*Lost
Record
o
W
o
(J _
so2
(23.7 ± 1.3 ppm)
EXPOSURE
so2
(37.3 ±0.5ppm)
EXPOSURE I
CONTROL
'O-O
S02
(26.9 ± 0.9ppm)
+ NaCI
(I0± 0.2mg/M3)
I EXPOSURE
PIO
*0-0-0
CONTROL
CONTROL
20
40
60
80
100
140 160
Time, Minutes
300
120
240
260
280
180
200
220
-------
TABLE 17
Cat No. '611
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Reiistance
Mech. %
Control Stim. Change
Low %
Control SO2 Change
Mech. %
Control Stim. Change
S0,+ %
Control NaCl Change
Mech. %
Control Stim. Change
17.7 135.6 666.1
17.7
Heani 17.7 135.6
S.D. 0
REFLEX INTACT
17.7 24.6 35.9
18.9 21.2 17.1
17.7 22.3 23.2
18.1 22.7
0.7 1.7
PO.05
17.7 167.4 845.8
17.7 167.4
REFLEX INTACT
17.7 25.7 45.2
17.7 22.2 25.4
17.7 22.3 26.0
17.7 23.4
0 2.0
P< 0.05
17.7 97.0 448
17.7 97.0
REFLEX INTACT
Lung Compliance
Mech. %
Control Stiin. Change
Low '1
Control SO2 Change
Mech. %
Control Stim. Change
S02+ %
Control NaCl Change
Mech. %
Control Stim. Change
Q.5 4.5 -52.6
9.1
leani P.5 h.5
S.D. 0
8.9 9.1 -9.6
8.8 8.6 -3.0
8.9 8.4 -5.3
8.7 8.U
0.1 0.3
A N. S.
9.1 4.8 -47.3
9.1 4.8
10.5 8.6 -11.9
10.0 8.2 -16.0
8.8 8.6 -11.9
9.8 8.5
0.9 3.2
L N. S .
9.8 4.6 -53.1
9.8 4.6
Sequence of v
Cftal lenge (')
(2) (3) (4) <5)
"^Control f^r t5 minutes preceding challenge.
(a) See Figure. fc N.S. = Oifference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm ^O/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
~ 135.6 167.4 ~ Q45.0 Q97
EXPOSURE RESPONSE PROFILE:
ANIMAL NO. ISM
26
26
3 o Pulmonary Flow Resistance
O o Lung Compliance
24
24
22
20
20
CO
S02 (2I.5± 0.5ppm) +
NaCI (10± 0.2 mg/M3)
EXPOSURE
S02 (21.5 ±2.8ppm)
EXPOSURE
CONTROL
CONTROL
CONTROL
5 14
P».
-o
-o
o—o
cr
-o-
80
20
30
70
Time, Minutes °4.8
40
50
60
90
100
110
120
130
140
150
4.6
-------
TA3LE 18
Cat No. »^78
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
(b)
Mech.
Control Stim.
%
Change
Low
Control SOj
%
Change
Mech. %
Control Stim. Change
Control
S02+-
NaCl
%
Change
Control
Mech.
Stim.
%
Change
22.it 115
413
17.5
16.9
18.7
21.2
17.3
21.2
19.8
-2.3
19.8
17.3 10*»
19
19
19
19
21.2
17.3
0
11.6
-8.9
17.7
89
403
lean! 22.4 115
S.D.
17.7
19.9
17-3 104
19.0
0
19.2
2.0
17.7
89
t-test REFLEX INTACT
A N.S.
REFLEX INTACT
A N.S.
REFLEX INTACT
Lung Compliance
Mech.
Control Stim.
%
Change
Control
Low
so2
%
Change
Mech. %
Control Stim. Change
Contro
S02+
NaCl
%
Change
Control
Mech.
Stim.
%
Change
22.6 33
-5
49.2
22.6
22.6
22.6
20.3
20.3
20.3
-10.2
-10.2
-10.2
19.4 12.8
22.6
22.6
22.6
17.7
17.7
17.7
-21.7
-21.7
-21.7
20.3
12.2
-39.9
wsan± 22.6 33
S.O.
.5
22.6
0
20.3
0
19.^ 12.8
22.6
0
17.7
0
20.3
12.2
t-tes t
P<0.01
P<0.01
Sequence
C&allen^e
(1)
(25
(3)
(4)
(5)
*Cnntrol far 15 minutes preceding challenge.
(a) See Figure. N.S. = Difference between means not sigiflcant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/'/sec.
(c) Lung Compliance, ml/cm h^O.
-------
TABLE 18 (Continued)
Cat No. T+78
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance ^
C i g. %
Control Smoke Change
Mech. %
Control Stim. Change
High %
Control SO2 Change .
17.it 13.1 -25.9
17.9 13.6 -22.9
12.3 -30.3
Mean! 17.7 13.0
S.D. O.k 0.7
t- tes t
15.2 77.9 321
20. 1
20. 1
IB.5 77.9
2.8
REFLEX INTACT
23.4 21.3 -6.0
21.2 18.3 -19.3
23.it lit.3 -36.9
22.7 18.0 '
1.3 3.5
A N.S.
Lung Compliance
Ci g. %
Control Smoke Change
Mech. %
Control Stim. Change
Hi gh %
Control SO2 Change
21.it 21.it 0
21.it 19.5 -13.6
1q.5 -13.6
Mean! 21 .it 19.5
S.D. 0
t-test
20.3 17.7 -7.3
18.5
18.5
19.1 17.7
1.0
16.3 : it. 6 - lit. 1
17.7 lit, ^ -1fa) f6)
Cfta I len0.05)
(b) Pulmonary Flow Resistance, Cm H^O/l/sec.
(c) Lung Compl i ance, ml/cm ^0.
-------
32
30
28
26
24
(
22
20
18
16
14
12
115
o
o 33.5
Q 104
~ 89
)
CO
CO
<
o
<
X
o
Ijj
s
EXPOSURE RESPONSE PROFILE
ANIMAL NO. 1478
o p Pulmonary Flow Resistance
o——o Lung Compliance
(/>
3
h-
CO
<
<_>
<
X
o
UJ
:£
CONTROL
S02
(23.7 ±0.7 ppm)
I EXPOSURE
CO
3
-I
3
2
h
(/>
U
llJ
O-Q-O -O-G—O—O
Q-
CONTROL
S02
(16.3 ± 3.2 ppm)
+ NaCI
(I0±0.2 mg/M
EXPOSURE
3)
o
CE
O
a
_L
_L
l
o
20 40 60 80 100
Time, Minutes
120
140
160
-------
TABLE 19
Cat No.32135
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Plow Resistance
(bj
Elec.
Control Stim.
%
Change
Control
Low
so2
V
Change
Control
Elec. %
Stim. Change
Contro1
E lec.
Stim.
%
Change
Control
S02 +
NaCl
%
Change
19 30.7
61 .6
11.6
9.7
9.2
11.8
12.5
12.5
7.6
14.0
1 it. 0
11.8
9.8
9.9 -8.3
1 1.2
9.8
11.1
10.4
-2.8
9.7
13-2
11.8
12.2
36. 1
21.6
25.
•"¦ea-.i 19 30.7
S.D.
KEFLEX INTACT
10.2
1.3
12.3
0.1*
A M.S.
10.8 9.9 '
1.4
REFLEX
QUESTIONABLE
10.7 10.4
0.8
REFLEX
QUESTIONABLE
9.7
12.4
0.7
P<0.05
Lung Compliance
E lec .
Control Stim.
%
Change
Control
Low
soP
:/
CKange
Control
Elec. %
Stim. Change
Control
Elec.
Stim.
%
Change
Control
S02 +
NaCl
%
Change
13.1 10.2
-22. 1
13.6
11.6
11.6
14.3
14. 0
12.7
13.2
14. 1
13.5
12.7
15.6
14.5 2.5
12
12
12
13.1
12
12
9-2
0
0
12
10.5
9.7
10
-12.5
-19.2
-16.7
t'ear.t 13. 1 ! 0. 2
S.C.
12.3
1.2
13-7
0.8
14.2
2.1
1'-+. 5
12.0
0
12.4
0.6
12.0
0
10. 1
0.4
t-test
A N.S .
P< 0.05
Sequence of , |
Cfcal 'sn^je 1
(1)
<2)
(3)
(4)
(5)
^Control for 15 minutes preceding challenge.
(a) See Figure. &N.S. = Difference between means not sigificant {P>0.05)
(b) Pulmonary Flow Resistance, Cm ^O./l/sec.
fc) Lung Compliance, ml/cm HjO.
-------
TABLE 20 ( Continued)
Cat No. 32135
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VAUJES*
Pu
Imonary Flow Reiistance
Elec. %
Control Stim. Change
%
Control NaCI Change
11.7 11*. 8 3.1
11.7
10.5
Meant 11.3 1U.8
S.O. 0.7
REFLEX
t-test QUESTIONABLE
11.7 11.3 0
11.7 1U.U 2 7. *~
10.5 12.1 7.1
11.3 12.6
0.7 1.6
£ N. S.
Lung Compliance
Elec. V,
Control Stim. Change
Control NaCI Change
12.7 11.6 -7.2
12.7
12.0
Meant 12.5 11.6
S.O. 0.1+
t-test
12.7 10.7 -1^.2
12.7 10.7 -lk.2
12.0 10.7 -1^.2
12.5 10.7
0.U 0
P<0.05
Sequence of .
Cfial 1en0.05)
(b) Pulmonary Flow Resistance, Cm HjO/l/sec.
(c) Lung Compliance* ml /cm H2O.
-------
I
24
Pulmonary Flow Resistance
o Lung Compliance
22 -
20
o-
o
®
« 18
in
I ZD
!»~
iCO
<
u
ia:
io
IlLl
|UI
{ft
-=>
_l
2
t—
U)
_J
<
u
QC
16
E
o
9
O
c
o
i 14
in
«
tr
*
o
u.
a
c
o
E
=i
a.
12
10
8
CONTROL
soz
(6.1 ± 0.3 ppm )
| EXPOSURE
_L
EXPOSURE RESPONSE PROFILE
ANIMAL NO.32135
CO
3
_l
z>
2
H
(A
-J
<
O
CJ
U1
llJ
q, o
V)
U
(-
CO
<
o
CJ
UJ
UJ
3
o-o—©
V
CONTROL
© ©
\
S02
5.9 ± 0.4 ppm)
¦+ NaCI
(I0±0.2 mg/M3)
EXPOSURE
t
NoCI
, (I0± 0.2 mg/M3)
CONTROL EXPOSURE,
24
22
20
18
O
CJ
X
E
16 £
w
u
14 J.
"o.
E
o
u
12 ?
10
8
20
40 60 80 100 120 (40
Time, Minutes
16C
(80
200
4
220
-------
TABLE 21
Cat No. 35354
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CJttNGE RELATIVE TO CONTROL VAUJES*
Pulmonary Flow Resistance ^
Elec. .%
Control Stim. Change
%
¦ Control SO? Change
S0,+ %
Control NaCl Change
' Elec. .%
Control Stim. Change
20.3 51.6 154
Meani 20.3. 51.6
S.D.
t-test REFLEX INTACT
21.8 27.9 18.7
25.5 ?7.9 18.7
23.2 27.9 1-8.7
23.5 27-9
1.9 0
A N.S. ¦
19.2 26.4 21.7
21.6 20.5 -5.5
24.4 20.8 -4.1
21.7 22.6
2.6 3.3
A N.S.
18.4 19.6 -10.1
23.0
24.0
21.8 19.6
3.0
REFLEX
QUESTIONABLE
Lung Compliance ^
Elec. %
Control Stim. Change
%
Control SO2 Change
so2+ %
Control NaCl Change
%
Control Stim. Change
10.9 10.5 -3.7
Meant 10.3 '0.5
S.D.
t-test
9.5 9.5 1.1
9.3 9.5 1.1
9.3 9.9 5.3
9.4 9.6
0.1 0.2
£> N.S .
10.7 10.0 -6.5
10.7 10.0 -6.5
10.7 10.4 -2.8
10.7 10.1
0 0.2
A N.S.
10.5 10.5 1.0
10. 1
10.7
10.-4 10.5
0.3
Sequence of v [ . .
'C6atlen«je | (1)
[2} (3) CO
*Contro1 for 15 minutes preceding challenge.
(a) See Figure. & N.S. = Difference between raeans not sigifleant (P>0.05)
(b) Pulmonary Flow Resistance, Cm HjO/l/sec.
(c) Lung Compliance* ml/cm t^O.
-------
~ 51.6 a 30.3
EXPOSURE RESPONSE PROFILE
ANIMAL NO. 35354
28
G Pulmonary Flow Resistance _
¦o Lung Compliance
26
CO
24
_ o
o
22
o
X
llJ
o
LlJ
o
o>
16 -J
S02
(I 3.7 ± 3.8 ppm)
+ NaCI
(I0± 0.2 mg/M3)
EXPOSURE
S02
(16.2 ± 6.7 ppm )
EXPOSURE
CONTROL
CONTROL
CONTROL
-3
0
10
20
30
90
110
120
130
140
150
50
60
70
80
100
Time, Minutes
-------
TABLE 22
Cat No. 1807
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
Mech. %
Control Stim. Change
High %
Control SO2 Change
Mech. %
Control St im. Change
%
Control NaC1 Change
Mech. %
Control Stim. Change
15. 4 55.1 +240.1
16.6
16.6
Meant 16.2 55.1
S.D. 0.7
t-test REFLEX INTACT
16.6 9.7 -41.6
16.6 12.3 -25.9
16.6 7.1 -57.2
16.6 9.7
0 2.6
P<-0.05
12.2 17.0 38.8
12.3
12.5 17..0
0.1
REFLEX
QUESTI0NA8EE
10.8 13.7 7.6
13.7 12.2 -4.2
13.7 13.7 7.6
12.7 13.2
1.7 0.9
A N.S.
12.3 31.8 158
12.3 31.8
REFLEX INTACT
Lung Compliance
Mech. %
Contro1 Stim. Change
High %
Control SO2 Change
Mech. %
Control Stim. Change
%
Control NaCI Change
Mech. %
Control Stim. Change
9.9 5.6 -43.4
9.9
9.9
Meant 9.9 5.6
S.D. 0
9.9 14.2 42.5
9.9 14.6 46.5
10.1 15.1 51.5
10.0 14.6
0.1 0.5
P<0.01
9.5 7.7 -42.8
17.4
13.5 7.7
5.6
14.2 11.7 -14.4
13.4 11.4 -16.6
13.-4 11.4 -16.6
13.7 11.5
0.5 0.2
P<-0.01
12.0 10.6 -11.7
12.0 10.6
Sequence of » j
CAallen^e | (1)
(2) (3) C») (5)
*Contro1 for 15 minutes preceding challenge.
(a) See Figure. a U.S. = Difference between means not sigiflcant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, m l/cm HjO.
-------
TABLE 22 (Continued)
Cat No. 1807
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pu
Imonary Flow Resistance ^
Cont ro1
13.6
16.3
13.7
Mean! 1 *+. 5
S.D. 1.5
Lung Compliance
Control
11.4
11.1
11. k
leant 11.3
3.0. 0.2
Sequence (6)
Cna 11en0.05)
(b) Pulmonary Flow Resistance, Cn ^O/l/sec.
(c; Lung Compliance, ml/cm HjO.
-------
0 w~-
n^l.O
EXPOSURE RESPONSE PROFILE
Pulmonary Flow Resistance
o Lung Compliance
5
o-o
S02
(35.6 ±2.5 ppm)
EXPOSURE
+ NaCI
(I0±0.2mg/M3)
EXPOSURE
CONTROL
CONTROL
CONTROL
80 100
Time, Minutes
120
140
160
160
-------
TABLE 23
Cat No. I486
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CWNGE RELATIVE TO CONTROL VAUUES*
Pulmonary Flow Resistance
(bj
Mech.
Control Stim.
%
Change
Control
so2+
NaC 1
%
Change
Control
Mech. 26
Stim. Change
Cont rol
Low
so2
%
Change
Control
25.6 128
27.0
27.9
376
2 9-2
31.0
29.8
3 2.2
33-8
30.2
7.3
12.7
0.7
28.5
29.2
117 302
35.9
24.7
26.9
26.4
-31.2
-25.1
-26.5
26.9
24.2
Meant 26.9
S.D. 1.2
30.0
0.9
32.1
1.8
29.1
0.2
117
35.9
26.0
1.2
25.5
t-test REFLEX INTACT
A N.S.
REFLEX INTACT
P< 0.01
k
Lung Compliance ^
Hech.
Contr o' Stim.
%
Change
Control
S0- +
NaCI
%
Change
Control
Mech. ^
Stim. Change
Control
Low
S02
%
Change
Control
5.3 3.
4.9
4.9
8
-2k. 5
5.0
5.0
5.0
4.5
4.6
4.6
-10.0
-8.0
-8.0
5.3
6.5
3.6 -40
8.1
6.2
6.0
5.6
-23.5
-25.9
-30.9
6.3
6.3
Meant 5.0
S.D. 0.2
5.0
0.0
4.5
0.1
5.9
0.8
3.6
5.9
0.3
6.3
t-test
P<0.01
P<
0.01
Sequence af »
Cfea 11en0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) lung Cocnpl i ance, ml/cm H^O.
-------
q 128 q"7
38
EXPOSURE RESPONSE PROFILE
ANIMAL NO. I486
22
36
a Pulmoncry Flow Resistance
o Lung Compliance
20
«/>
34
g
2 32
-------
TABLE 24
Cat No. 1144
RESPONSE TO VARIOUS STIMULI EXPRESSEO AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Control
Pu
1 nonary Flow Resistance
'lech. Percent
Stim. Chanoe
Low Percent
Control SO? Change
t
Mech. Percent
Control Stim. Chanqe
S02+ Percent
Control NaCl Change
Mech. Percen t
Control Stim. Change
30.2 131 326.7
31.2
lean- 30.7 131
5.0. 0.7
t-test REFLEX INTACT
34.6 41.8 19,5
33.8 40.5 15.8
36.5 40.5 15.8
35.0 40.9
1.4 0.8
P<0.01
35.2 99.3 182.1
35.2 99.3
REFLEX INTACT
47.9 45 11.7
36.5 ^5 11.7
36.5 45 11.7
40.3 45.0
6.6 0
A N.S.
43.5 81*.7 94.7
43.5 81*.7
REFLEX INTACT
Lung Compliance
Mech. Percent
Control" Stim. Change
Low Percent
Control SO2 Change
Mech. Percent
Control Stim: Change
SO2+ Percent
Control NaCl Change
Mech. Percent
Control Stim. Change
5.8 4.2 -28.°.
6.0
leant 5.9 *+.2
0.1
:-test
6.4 6.7 3.1
6.6 6.4 -1.5
6.6 6.4 -1.5
6.5 6.5
0.1 0.2
A N. S.
7.8 4.0 -48.7
7.8 4.0
6.4 5.9 -6.3
6.3 5.9 -6.3
6.2 5.9 -6.3
6.3 5.9
0. 1 0
p< 0.05
6.4 4.4 -31.3
6.4 4.4
Sequence of ^
Cfcallenqe '
*Contro1 for 15 minutes preceding challenge.
(a) See Figure. &N.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm h^O/l/sec.
(c) Lung Cnmoliance, ml/cm 1^0.
-------
TABLE 24 (Continued)
Cat No. 1144
RESPOHSE TO VARIOUS STIMULI EXPRESSEO AS PERCENT CHANGE RELATIVE TO CONTROL VAUJES*
Pulmonary Flow Resistance ^
High Percent
Control S02 Charge
40.5 55.3 46,2
36.5 47.1 2k.S
36.5 45 >8.9
leant 37.8 k9.)
5.0. 2.3 5.4
t-test P<0.05
Lung Compliance
High Percent
Control SOj Change
5.Q 6.0 2.3
5.9 5.9 0.6
5.9 5.9 0.6
¦lean* 5.8 5.9
>.0. 0.1 0.1
t-test A N.S.
Sequence
Cftallenqe
. .....
*Cnntrol for IS minutes preceding challenge.
(a) See Figure. A N.S. = Difference between means not slgiflcant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm
-------
TABLE 25
Cat No. 2593
RESPONSE TO VARIOUS STIHULI EXPRESSED AS PERCENT CWNGE RELATIVE TO CONTROL VALUES
Pulmonary Flow Resistance
Low Percent
Control SO2 Change
High Percent
Control SOj Chan-j^
Control
47.4 3J.8 -25.5
39.* 3L.9 -IB.3
4'.1 36.4 -1^.8
Me.in+ k?.7 34.
S.D. 4.1 2.3
t-test P<0.05
45.8 US.C- 4.8
44,2 48.9 11.9
41.1 47.3 8.2
43.7 . 47.3
2.4 1.6
1N.S.
48.9
48.9
Lung Compliance
Low Percent
Control SOj Change
Hj gh Percent
Control SO2 Change
Control
7.8 8.2 -4.7
9,2 8.7 1.2
8.8 8.4 -2.3
Meanl^ 8.6 8.4
S.D. 0.7 0.3
t-test A *1.5.
8.6 8.7 -0.8
8.7 8.6 -1.9
9.0 9.5 8.4
8.8 8.9
0.2 0.5
L N . S .
9.5
9.5
Sequence of \
C&a 1 leriqe
^Control for IS minutes preceding challenge.
(a) See Figure.
(b) Pulmonary Flow Resistance, Cm I^O/l/sec.
(c) Lung Compliance, ml/cm ^0.
fiN.S. = Difference between means not sigificant (P>0.05)
-------
TABLE 26
Cat No. 1988
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pu
Imonary Flow Resistance
Mech. Percent
:Control Stim. . Change
High Percent
' Control SO, ' Change
Mech. Percent
Control Stim. Change.
Percent
Control NaCI Change
Mech. Percent
Control Stim. Change
64.2 130.5 112.0
5*. 9
Mean! 61.6 130.5
S.D. 3.7
t-test REFLEX INTACT
53.1 31.8 -39.4
51.1 35.6 -32.1
53.1 -3-1.8 -39.4
52.4 33.1
1.2 2.2
P<0.01
27.7 73.7 166.1
27.7 73.7
REFLEX INTACT
22.1 18.2 -33.2
29.8 18.2 -33.2
29.8 24.0 -11.9
27.2 20.1
4.4 3.3
A N.S.
22.? 49.3117.2
22.7 49.3
REFLEX INTACT
Lung Compliance
Mech. Percent
Control Stim. Change
High Percent
Control SO2 Change
Mech. Percent
Control Stim.' Change
Percent
Control NaCI Change
Mech. Percent
Control Stim. Change
3.9 3.3 -15.4
3.9
Mean^ 3.9 3.3
0.0
t-test
4.3 5.2 20.9
4.3 5.4 25.6
*~. 3 8.4 95.3
4.3 6.3
0.0 1.8
-N.S.
6.1 3.3 -45.9
6.1 3.3
7.6 7.6 2.7
7.4 7-2 -2.7
7.2 7.2 -2.7
7.4 7.3
0.2 0.2
A N.S.
7.4 4.3 -41.9
7.4 4.3
Sequence of.
Challenge
*Control for T5 minutes preceding challenge.
(a) See Figure. & N.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE 26 (Continued)
Cat No. 1988
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance
S02+ Percent
Control NaCl Change
Mech. Percent
Control Stim Change
Percent
Control SO2 Change .
Mech. Percent
Control Stim. Change
27.9 27.3 -2.1
29.5 27.8 -2.1
27.8 31.2 9.9
Meant 2S.it 28.9
S.D. 1.0 2.0
t-test liN.S.
2U.1 33. 1 3£t.O
2k.1 33.1
REFLEX
QUESTIONABLE
26.2 26.2 -1.9
27.7 30.7 15.0
26.2 31.8 19.1
26.7 29.6
0.9 3.0
A N.S.
29.8 97.6 227.5
29.8 97.6
REFLEX INTACT
Lung Compliance ^
S02+ Percent
Control MaCI Change
Mech. Percent
Control Stim. Change
Percent
Control SO2 Change
Mech. Percent
Control Stim. Change
7.h 5.^ -22.9
7.0 S.h -22.9
6.6 5.2 -25.7
Mean! 7.0 5.3
S.D. Q.k 0.1
t-test P< 0.01
5.9 5.it -8.5
5.9 S.k
S.k k.9 -10.9
5.6 k.9 -10.9
5.6 5.0 - 9.1
5.5 k.9
0.1 0.1
0.01
5.7 k.3 -2k.6
5.7 k.3
Sequence of^ J
Cftallenqe |
^Control for IS minutes preceding challenge.
(a) See Figure. aN,S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm 1^0.
-------
TABLE 27
Cat No. 1801
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO COffTROL VAWES*
Pulmonary Flow Re*istance
lb)
Mech.
Control¦Stim.
%
Change
Control
Hi gh
so2
%
Change.
Mech. %
Control Stim. Change
. Control
NaCI
%
Change
Control
Mech.
.Stim.
%
Change
23.3 33
23'6
.7
*~3.7
18.1
23.6
23.6
18.1
25.3
22.0
-16.8
16.2
1.1
23.6 45 90.7
2>.0
23.6
25.3
45.8
56.4
61 .4
93.8
133.6
159.8
46.6
89.6
92.3
Meant 23.5 33
S.O. 0.2
.7
21.8
3-2
21.8
3.6
23.6 45.0
23.6
1.7
54.5
8.0
46.6
89.6
REFLEX INTACT
A N.S.
REFLEX INTACT
P<0.05
REFLEX INTACT
Lung Compliance ^
Mech.
Control Stim.
Change
Control
Hi gh
S02
%
Change
Mech. %
Control Stim.Change
Cont'd
NaCI
%
Change
Control
Mech.
Stim.
%
Changes
6.3 4.
6.2
9
-21.6
5.2
5.4
5.4
6.0
5.7
5.^
12.5
6.9
1.3
6.0 5.7 -5.0
5.7
5.6
5.4
4.7
4.6
4.5
-15-6
-17.4
-19.2
4.8
4.8
0
lean! 6.2 4.
S.D. 0.1
9
5.3
0. 1
5.7
0.3
6.0 5.7
5.6
0.2
4.6
0.1
4.8
4.8
A N.S.
P<0.01
Sequence
CRa1 len^je
¦ P)
(2)
(3)
(4)
(5)
^Control for 15 minutes preceding challenge.
(a) See Figure. tiN.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm HjO/'/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE 27 (Continued)
Cat No. 1801
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pu
Imonary Flow Resistance *b'
S02+ %
Coitro! NaCl Change
Hech. %
Control Stim. Change
%
Control SO2 Change
Mech. %
Control Stim. Change
?3.6 25.3 -2.7
23.6 23.9 -8.1
30.8 21.0 -19-2
Meant 2 6. 0 23.4
S.O. 4.2 2.2
A N.S.
25.3 57.0 125.3
25.3 57.0
REFLEX I NTACT
22.0 25.3 15.0
22.0 28.6 30.0
22.0 32.6 48.2
22.0 2-3.8
0.1 3.7
A N.S.
21.4 64.5 201.4
21.4 64.5
REFLEX INTACT
Lung Compliance
S02+ %
Control NaCl Change
Mech. %
Control Stim. Chsng.-:
%
Control SO2 Change
Mech. %
Control Stim. Change
5.9 ft.3 -20.4
5.6 *4.3 -2 0.4
4.7 4.3 -?0.4
Meani 5.4 4.3
0.6 0
A N.S.
5.1 5.2 2.0
5.1 5.2
5.0 4.2 -12.5
4.7 4-0 -16.7
4.7 4.2 -12.5
4.8 4.1
0.2 0.1
P<0.01
4.9 4.9 0
4.9 4.9
Sequence of.
Cftal lenfle
(6)
(7) (8) (9)
^Control for 15 minutes preceding challenge.
(a) See Figure. a N.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm HjO.
-------
TABLE 28
Cat Mo. 1781
response to various stimuli expressed as percent change relative to control values*
Pulmonary Flow Resistance
Mech. %
Control Stim. Change
Hi gh %
Control SO? Change
Mech. %
Control Stim. Change
26.1 30.6 177.9
Meant 29.0 BO.6
S.O. I*.l
t-test REFLEX INTACT
M.U
7.2 6.6
0.1 . 0.1
P<0, 01
6.7 5.6 -I6.it
6.7 5.6
Sequence of . . .
CRal len^je (1J
fi) (3)
*Contro1 for 15 minutes preceding challenge.
(a) See Figure. tt.N'.S. = Difference between means not slgfficant (P>0.05)
(b) Pulmonary Flow Resistance, Cm ^O/l/sec.
fc) Lung Compliance, ml/cm V^O.
-------
TABLE 29
Cat No. 2206
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Resistance v '
^U2
Both Percent
Control Sites Change
SO2 Percent
Control Kouth Change
SO2 Percent
Control Trachea Change
Contr ol
W+.6 37.3 -16.1+
W+.6 1+2.2 -5.1+
kh.o 1+2.2 -5.1*
Meani kh.6 1+0.6
S.D. 0.0 2.8
t-test A N.S.
M+.6 3k.3 -21.7
kh.S 37.3 -16.1+
1+4.6 3^.' -23-5
1+1+.6 35. k
0.0 1.7
p< 0.05
1+4.6 32.5 -27.1
1+1+.6 27.3 -38.8
M+.6 30.0 -32.7
1+1+.6 29.9
0.0 2.6
P< 0.05
1+2.2
42.2
Lung Compliance
iU2
Both Percent
Control Sites Change
SO2 Percent
Control Mouth Change
SO2 Percent
Control Trachea Change
Control
5.3 1+.6 -i6.lt
5.6 1+.5 -18.2
5.6 5.0 - 9.1
Mean- 5.5 1
S.D. 0.2 0,3
t-test P<0.01
5.2 5.8 8.8
5.5 5.3 -0.6
5.3 5.6 5:0
5.3 5.6
0.2 0.3
iN.S.
5.6 5.0 -10.7
5.6 1+.8 -11+.3
5.6 5.0 -10.7
5.6 5.0
0.0 0.1
P< 0.01
5.0
5.0
Sequence of > \
CF»a1 len0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml /cm HjO.
-------
TABLE 30
Cat Ho. 53869
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO CONTROL VALUES*
Pulmonary Flow Ret(stance
SO?
Both Percent
Control Sites Change
SO2 Percent
Control Mouth Chanqe
SO2 Percen1
Control Trachea Chang
Control
9.6 13.5 M*.6
8.9 ..ji»,2 52.1
9.6 13.5 M*. 6
Meant 9.3 13.7 .
S.D. 0.5 - O.it
t-test P<0.01
9.6 13.6 41.7
9.6 11.8 22.9
9.6 12.0 25.0
9.6 12.5
0.0 1.0
P< 0.05
10.9 13.5 23.9
10.9 1^.2 30.3
10.9 12.9 18.3
10.9 13.5
0.0 0.7
P< 0.05
12.3
12.3
Lung Compliance
so2
Both Percent
Control Sites Change
SOj Percent
Control Mouth Chanoe
SO2 Percent
Control Trachea Chanae
Control
22.7 19.4 -1^.5
22.7 19.fc -H».5
22.7 20.2 -11.0
Meant 22.7 19.7
0.0 0.5
t-test P< 0.01
22.7 18.1 -20.3
22.7 19.!+ -Tt.5
22.7 18.7 -17.6
22.7 18.7
0,0 0.7
P<0.01
19.^ 15.9 -19.2
19.^ I6.it -16.6
20.2 15.9 -19.2
19.7 16.1
0.5 0.3
P
Cftal len«je
*Contro1 for 15 minutes preceding challenge.
(a) See Figure. ^ N*S. = Oifference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Compliance, ml/cm f^O.
-------
TABLE 31
Cat No. 298*4
RESPONSE TO VARIOUS STIMULI EXPRESSED AS PERCENT CHANGE RELATIVE TO COKTROL VALUES*
Pu
Imonary Flow Resistance
SOo Percent
Control Trachea Change
SO2 Percent
Control Mouth Change
SU2
Both Percent
Control Sites Change
Control
42.2 25.7 -39.1
<+2.2 2 3.0 -<+5.5
1+2.2 23.0 -45.5
fear-it 42.2 23-9
S.D. 0.0 1.6
t-test P< 0.01
<+2.2 39.4 "6.6
<~2.2 42.2 0
<+2.2 <+2.2 0
42.2 41.3
0.0 1.6
is N. S .
42.2 23.0 -45.5
42.2 21.9 -48.1
42.2 25.3 -40.0
42.2 23.4
0.0 1.7
P< 0.01
36.7
36.7
Lung Compliance
SO2 Percent
Control Trachea Change
SO2 Percent
Control Mouth Change
so2
Both Percent
Control Sites Change
Control
5.3 5.6 0.6
5.4 5.6 0.6
6.0 5.6 0.6
*eant 5.6 5.6
0.4 0.0
t-test i N,S.
5.3 6.7 14.9
6.4 6.9 13.3
5.8 6.7 14.9
5.8 6.8
0.6 0.1
i N.S.
6.0 5.8 -8.9
6.4 5.6 -12.0
6.7 5.8 -8.9
6.4 5.7
0.4 0.1
A N.S.
8.2
8.2
Sequence of ^
Cfiallen^e
*Control for 15 minutes preceding challenge.
(a) See Figire. fiN.S. = Difference between means not sigificant (P>0.05)
(b) Pulmonary Flow Resistance, Cm H20/l/sec.
(c) Lung Coriplionce, ml/cm HjO.
-------
THE FOLLOWING PAG ES ARE DUPLICATES OF
ILLUSTRATIONS APPEARING ELSEWHERE IN THIS
REPORT. THEY HAVE BEEN REPRODUCED HERE BY
A DIFFERENT METHOD TO PROVIDE BETTER DETAIL
-------
IV-• ••" "" • -
• • W\
¦\\Y
g-Sa«
g o <0
r- 3 ^ mj*
til «*
g-^3
1^1
O
BP Blood Pressure
TPP Transpulmonary Pressure
V Air Flow
V Volume
Rl Pulmonary Flow Resistance
Lung Compliance
-------
A Statham Transducer (TPP)
B Fleisch Pneumotachograph
C Statham Transducer (V and V)
D Harvard Pump
-------
ALVEOLUS
ALVEOLAR DUCT
ALVEOLAR SAC
INTERALVEOLAR SEP
TUM. X130.
E
-------
ALVEOLUS
ALVEOLAR DUCT
ALVEOLAR SAC
INTERALVEOLAR SEP
TUM. X130.
-------
ALVEOLUS
ALVEOLAR DUCT
BRONCHIOLE
BLOOD VESSEL
CARTILAGE
EPITHELIUM
SMOOTH MUSCLE. X130.
M 2" 3
" §-ou
H- •"»"> p
IN!
^ 5
M ®
S ® 8
^ fr*1
3
3 a,
§*&it
-------
Patho-Physiologic Response to Single and
Multiple Air Pollutants in Humans and Animals
------- |