United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangia Park NC 27711
EPA-600/1-79-037
September 1979
Research and Development
Low-Level Carbon
Monoxide Exposure
and Work Capacity
at 1600 Meters
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RESEARCH REPORTING SERIES
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EPA-600/1-79-037
September 1979
LOW-LEVEL CARBON MONOXIDE EXPOSURE
AND WORK CAPACITY AT 1600 METERS
Philip C. Weiser
Gerd J.A. Cropp
Call is G. Morn" 11
Thomas L. Kurt
David W. Dickey
Department of Physiology
National Asthma Center
1999 Julian Street
Denver, Colorado 80204
Contract No. EPA 68-02-2244
Project Officer
Edward Haak
Clinical Studies Division
Health Effects Research Laboratory
Research Triangle Park, NC 27711
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
HEALTH EFFECTS RESEARCH LABORATORY
RESEARCH TRIANGLE PARK, NC 27711
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DISCLAIMER
This report has been reviewed by the Health Effects Research Laboratory,
U.S. Environmental Protection Agency, and approved for publication. Approval
does not signify that the contents necessarily reflect the views and policies
of the U.S. Environmental Protection Agency, nor does the mention of trade
names or commercial products constitute endorsement or recommendation for
use.
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FOREWORD
The many benefits of our modern, developing, industrial society are
accompanied by certain hazards. Careful assessment of the relative risk of
existing and new man-made environmental hazards is necessary for the estab-
lishment of sound regulatory policy. These regulations serve to enhance the
quality of our environment in order to promote the public health and welfare
and the productive capacity of our Nation's population.
The Health Effects Research Laboratory, Research Triangle Park, conducts
a coordinated environmental health research program in toxicology, epidemio-
logy, and clinical studies using human volunteer subjects. These studies
address problems in air pollution, non-ionizing radiation, environmental
carcinogenesis and the toxicology of pesticides as well as other chemical
pollutants. The Laboratory participates in the development and revision
of air quality criteria documents on pollutants for which national ambient
air quality standards exist or are proposed, provides the data for registra-
tion of new pesticides or proposed suspension of those already in use,
conducts research on hazardous and toxic materials, and is primarily respon-
sible for providing the health basis for non-ionizing radiation standards.
Direct support to the regulatory function of the Agency is provided in the
form of expert testimony and preparation of affidavits as well as expert
advice to the Administrator to assure the adequacy of health care and
surveillance of persons having suffered imminent and substantial endanger-
ment of their health. '
Results of two studies are discussed on the following pages. The
initial study investigated nine, non-smoking, male subjects breathing either
filtered air (FA) or 28 ppm CO in filtered air. The dose-response study
exposed twelve subjects to FA or CO such that the end-exercise HbCO levels
were 0.7, 3.5, 5.4, and 8.7 percent HbCO.
F. Gordon Hueter, Ph.D.
Director
Health Effects Research Laboratory
iii
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ABSTRACT
At sea level, low-level carbon monoxide (CO) exposure impairs exercise
performance. To determine if altitude residence at 1600 m augments this CO
effect, two studies of graded treadmill work capacity were done. The
Initial Study investigated nine, non-smoking, male subjects breathing
either filtered air (FA) or 28 ppm CO in filtered air. End-exercise
carboxyhemoglobin (HbCO) levels averaged 0.9 %HbCO breathing FA and 4.7.
%HbCO breathing CO. Total work performance and aerobic work capacity were
reduced. Work heart rate was elevated, and post-exercise left ventricular
ejection time breathing CO did not shorten to the same degree as with FA
exposure. CO exposure resulted in a lower anaerobic threshold, and a
greater minute ventilation occurred at work rates heavier than the anaerobic
threshold due to an increased blood lactate level. The Dose-Response Study
exposed twelve subjects to FA or CO such that the end-exercise HbCO levels
were 0.7, 3.5, 5.4 and 8.7 %HbCO. Exercise performance and aerobic work
capacity were impaired in proportion to the CO exposure. In both studies,
maximal cardiopulmonary responses were not different, but submaximal
exercise changes were elevated breathing CO. Thus, in healthy young men
residing near 1600 m, an increase in low-level CO exposure produced a
linear decrement in maximal aerobic performance similar to that reported at
sea level.
IV
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ACKNOWLEDGMENTS
The authors would like to recognize and thank the following for
their assistance in the projects: Ronald McEntaffer, Patricia Schor,
Steven Getz, and Geoffrey Kampe for their technical work; Renee Kirklin,
Constance Yearling and Joanna LaRose for their secretarial help; and
Dr. Gary Zerbe for his advice and help during the data analysis.
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CONTENTS
Foreword iii
Abstract iv
Acknowledgments v
List of Figures vii
List of Tables viii
Secti ons
1. Introduction 1
2. Conclusions 3
3. Recommendations 4
4. Experimental Design and Methods 5
5. Results 9
6. Comments 21
7. References 25
VI
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FIGURE
Number Page
1 Increasing- blood carboxyhemoglobin levels (HbCO) decreases
physical work capacity (Vn max). 22
vn
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TABLES
Number Page
1. Initial Study—blood carboxyhemoglobin levels 11
2. Initial Study—changes in exercise performance 12
3. Initial Study—heart rate and ventilatory adaptations to
maximal aerobi c work 13
4. Initial Study—effects of CO exposure during submaximal
14
exerci se 1H
5. Initial Study—change in systolic time intervals 15
6. Dose-Response Study—blood carboxy hemoglobin levels 17
7. Dose-Response Study—change in exercise performance 18
8. Dose-Response Study—heart and ventilatory adaptations to
maximal aerobic work 19
9. Dose-Response Study—change in systolic time intervals 20
vm
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SECTION I
INTRODUCTION
Ambient Air Quality Standards (AAQS) have been established to protect,
with a reasonable margin of safety, susceptible segments of the population
as well as healthy individuals from the harmful effects of air pollution.
The present AAQS for carbon monoxide (CO) is 9 ppm averaged over an eight
hour period and 35 ppm averaged over a one hour period. These levels of
CO and exposure times are sufficient to increase the blood carboxyhemo-
globin concentration (HbCO) about 1.5%. The AAQS have been established,
however, from data acquired from sea-level studies. Information necessary
to adequately evaluate any additional risk factors for sojourners or
residents during CO exposure at altitude does not exist.
Acute exposure to CO impairs exercise performance as measured by
maximal aerobic power (v"02 max) at sea level (2,8,12,14,18,19). The
threshold for a statistically significant decrease in \IQ^ max appears to
be at a HbCO level of 4.0% (2,12). Above this level, the decrease in VO
max is proportional to the HbCO level (2,17).
Hypobaric hypoxia that occurs at altitude also impairs maximal
aerobic power. The threshold for an altitude-induced decrease in V0? max
is at an elevation of 1600 m. Above this altitude, the loss of V02 max
is proportional to the decrease in inspired oxygen tension (5,10).
The purpose of this study was to determine if the effects of low-
level CO exposure upon aerobic work capacity would be augmented in healthy
young men who reside at an altitude of 160m (Denver). Their aerobic work
capacity was measured using graded treadmill tests with and without CO
exposure. Also, the electrocardiogram and systolic time intervals were
investigated also to determine if decrements in cardiac function occurred.
In the initial research research study, 9 healthy young males had their
maximum oxygen consumption measured four times: twice while breathing
filtered air, and twice while breathing ambient air which contained
-------
sufficient CO to maintain a blood concentration of 5% HbCO after a quick
CO loading. In a subsequent dose-response study, 12 healthy young males
performed maximal exercise tests at each of four different levels of HbCO.
Each subject was exposed randomly to filtered air, nearly free of CO, and
to sufficient CO in the other three experiments to maintain venous COHb
levels of approximately 4, 6, and 9% HbCO after quick CO loading. The
results of these tests were analyzed to determine the effects of low-level
CO concentrations on exercise performance and cardiac function in healthy
young males acclimated to residence at 1610m.
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SECTION II
CONCLUSIONS
At an altitude of 1610m (Denver, Colorado), a proportional reduction
of total exercise time, total vertical work done, and final work rate
was found when the HbCO level was increased from 1% to 9% HbCO.
Maximal aerobic work capacity, measured as Vn max, decreased linearly
2
with the level of CO exposure.
Although work capacity during CO exposure was reduced, maximal heart
rates, maximal minute ventilations, peak venous lactates, and oxygen
debts were not significantly different suggesting that CO exposure
provoked a greater cardio-respiratory adaptation at a given submaximal
workload.
At 3-4 minutes post-exercise, left ventricular ejection time was not
shorted as much during CO exposure as it was during FA breathing.
This finding has also been reported for patients reporting chest pain
during exercise.
The changes found in exercise performance and cardiac function during
CO exposure were comparable to those reported in sea level studies.
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SECTION III
RECOMMENDATIONS
1. Since it is believed that the rate of CO uptake is increased as the
partial oxygen pressure level decreases, i.e., the higher the altitude,
then a test of this hypothesis should be made in Denver residents
before any affirmation or modification of the current AAQS for 1600m
is made.
2. Since Denver's elevation is at the threshold for altitude-induced
aerobic work capacity decrement, then both the exercise performance
and cardiac function of residents at a higher elevation, e.g., Lead-
vine (3100m), and sojourners from Denver altitude to that higher
altitude should be studied.
3. Since the oxygen supply to the heart tissue, especially in heart
patients, is crucial to work performance, the effect of CO on angina-
limited exercise in patients living at Denver altitude should be
studied.
4. Since patients with chronic obstructive pulmonary disease living in
Los Angeles show a remarkable loss of work capacity when exposed to
low CO level, patients with lung disease who reside in Denver should
be studied to determine if altitude aggravates exercise-induced
breath!essness.
5. Since the blood supply to the brain is crucial, the effects of CO
exposure on judgment should be studied in asymptomatic 50-to-60 year
old individuals who live in Denver.
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SECTION IV
EXPERIMENTAL DESIGN AND METHODS
1. Initial Study
We studied nine healthy, male volunteers with a mean (+SEM) age of
24.7 +_ 1.4 years, height of 178 +_ 2 cm, and weight of 76.6 +_ 3.1 kg.
Analysis of variance showed no significant change in the subjects' weights
during the study. All subjects were non-smokers. Informed consent was
obtained from all the subjects. Before participating actively in the
study, each subject was given a preliminary physical examination which
included a resting 12-lead electrocardiogram (ECG), pulmonary function
evaluation, blood analysis, preliminary exercise ECG, and graded stress
test to VQp ma*.
In the study itself, each subject exercised four times, twice breathing
filtered air (FA) and twice breathing air containing CO. These four
sessions were divided into two pairs, with each pair consisting of one FA
and one CO experiment. The order of FA and CO experiments in each pair
was assigned in a double-blind fashion.
In each experimental session, the same protocol was used. Following
resting 12-lead ECG and systolic time interval (STI) measurements, a
forearm venous blood sample was taken and analyzed for HbCO. The initial
HbCO estimate was always made on a CO-Oximeter (Instrumentation Laboratory)
with the more accurate HbCO measurement made later using a gas-chromatograph
technique which was modified for use with a flame-ionization detector
(Baseline Industries). The desired blood HbCO concentration was obtained
quickly in the CO experiments by having the subject rebreath from a
closed-circuit system to which a bolus of 100% CO had been added (7).
The volume CO required to increase the subject's HbCO level to 5% was
calculated from a preliminary estimate of total body hemoglobin. About
90% of the calculated CO volume was added to a 4.2 liter rebreathing
circuit over a 1-3 minute period. After 8 minutes of rebreathing, another
-------
venous blood sample was taken, and the HbCO level measured. Additional
CO was administered at that time if needed to achieve the 5 %HbCO level.
The total volume of 100% CO administered ranged from 37 to 53 ml (STPD).
A third blood sample was taken at the end of the 20 minute rebreathing
period to determine the final pre-exercise HbCO level. For the remainder
of the experiment, the subject breathed from an open-circuit system.
This system provided the inspired CO level that was required to maintain
the desired HbCO for that experiment. Throughout the experiment, the
inspired and expired CO levels were monitored by a long-path infrared
analyzer (Beckman, Model 315B).
Maximal oxygen consumption (tfcu max) was measured using a modified
incremental treadmill test (4). The work test was preceded by a 9 minute
resting period with the subject in the supine position. The subject
began the test by walking for 4 minutes at 2.0 mph on a Q% grade. The
treadmill speed was then increased at 2 minute intervals, to 3.0 and 3.75
mph. At 3.75 mph, the grade was increased 2% every 2 minutes until the
subject could no longer continue or until the treadmill had reached its
maximum grade of 20%. If the subject could still exercise at a 20%
grade, then the speed was increased every 2 minutes to 4.5, 5.0, and 5.5
mph until the subject's maximal performance was reached. Following
exercise, the subject walked slowly in place for 1-2 minutes and then
rested in the supine position for the remainder of the 60 minute recovery
period.
During the exercise tests, minute ventilation (VL, BTPS), the
expired air fractions of oxygen (F^Oo) and carbon dioxide (FECQ ), and
heart rate (HR) were measured. These data were processed by an on-line
digital computer (Health Garde), which calculated oxygen consumption and
other parameters. During the 9 minute pre exericse rest period, computer
data sampling was done over the last two minutes of each three minute
interval. For work rates producing a HR of less than 180 bpm, the second
minute of each 2-minute period was sampled. For heavy work producing a
HR above 180 bpm, sampling was done over the last twenty seconds of each
work minute. For the first six minutes following exercise sampling was
done over the last 20 seconds of each minute. Thereafter during the
-------
recovery period, the sampling intervals were progressively lengthened. A
blood sample was taken every fourth minute during exercise and at the
fourth minute of recovery.
Minute ventilation was measured in a 120 liter gasometer (Tissot,
Collins), and respiratory rate was obtained by monitoring inspiratory
flow with a Fleisch pneumotachygraph (Instrumentation Associates) that
was connected to a differential strain gauge (PM197, Statham). Expired
gas was analyzed for FECC^ and F£°2 by a mass sPectrometer (Model 1100,
Perkin Elmer) which sampled expired gas from the outlet of a 9 liter
mixing chamber. Heart rate was obtained from the ECG recordings.
Venous blood samples were analyzed for pH (Radiometer), lactate (Sigma),
2,3-diphosphoglycerate (Sigma), hemoglobin by the cyanmethemoglobin
method, and hematocrit by the microhematocrit method.
During the twelve minutes which preceded the sub-maximal exercise,
resting, baseline measurement were made. Ventilation was measured over
the last two minutes of successive three-minute intervals and a blood
sample was drawn during the last minute of the rest period. Submaximal
exercise followed the rest with each subject walking continuously for 12
minutes at 5.3 kilometers per hour. The submaximal work intensity
(treadmill grade) was adjusted for each subject to produce a heart rate
between 100 and 120 bpm at the end of a FA test. The submaximal work was
set at the same intensity for each of the four exercise tests for a given
subject. Ventilation was measured the last minute of successive two-
minute intervals and blood was drawn at the end of the fifth and twelth
minutes of the submaximal test. The treadmill and monitoring were then
stopped for four minutes while the equipment was recalibrated. The
subject came off the mouthpiece for the first minute of the recalibration
period. After recalibration, maximal oxygen consumption was measured
using a modified incremental treadmill test (11). The subject ran at a
constant rate of 10.5 kph (6.5 MPH) and the initial treadmill grade was
the same as that during the submaximal walking test. The grade was
increased by 2.5% every two minutes until the subject became exhausted
and could no longer continue to exercise at such a rate. Data was
collected over the last 27 seconds of each minute period. No blood
-------
samples were taken during the maximal test. The subject remained on the
breathing system for a sixteen minute recovery period after the maximal
test. The first part of recovery consisted of four, one-minute periods,
with 27 second collections. This was followed by six, two-minute periods,
with 60 seconds collections over the second minte. Blood samples were
drawn and measurements for STI calculations were made at the 2nd, 4th,
8th, and 15th minutes of recovery.
The following parameters were monitored on-line using a digital
computer (Health Garde): minute ventilation by gasometer (Tissot,
Collins); respiratory rate with a Fleisch pneumotachygraph (Instrumentaton
Associates) in series with a differential strain gauge (Statham Model
515); and mixed expired oxygen and carbon dioxide concentrations sampled
from a 9 liter chamber by a mass spectrometer (Perkin Elmer, Model
1100). Using these signals, the computer calculated values for oxygen
consumption.
3. Statistical Analysis
The data were analyzed using a one-way analysis of variance with
repeated measures across all exposure conditions (FA vs 5% CO for the
initial study; FA,3%, 6%, vs 9% for the dose-response study). When the
F-value was significant at the 5% level, an orthogonal comparison between
the individual means was made (20, pp. 171-175). For these analyses, the
selected variables included all physiological variables measured at
max and the venous blood variables measured immediately following the
exercise test.
8
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SECTION V
RESULTS
A. Initial Study
Changes in HbCO during the experiments are shown in table 1. The CO
bolus increased HbCO from about 1.0% to about 5.1% HbCO. Maximal exercise
during FA breathing significantly decreased HbCO by approximately 0.1% Hb.
During exposure to 28 ppm CO, light exercise significantly decreased HbCO
by about 0.2% Hb and maximal exercise decreased HbCO by an additional
0.4% Hb.
Exercise performance was decreased by CO exposure (Table 2). Total
exercise time was significantly decreased by 3.8% from an average of 27.0
minutes for the two FA experiments to an average of 26.0 minutes for the
CO experiments. Total vertical work done during uphill walking or running
(i.e., at a work rate of 3.75 mph, 2% grade or greater) was significantly
4
decreased by 10.0% from an average of 1.40 x 10 kpm for the FA experiments
4
to 1.26 x 10 kpm for the CO experiments. These changes in work done were
•
also associated with a significant 3.5% decrease in Vc^ max.
Although both the total vertical work done and VQ2 max were reduced
during CO exposure, other physiological variables measured at the end of
the work capacity tests were not significantly changed (Table 3). Both
the maximal heart rate and maximal minute ventilation during CO exposure
were not different from the FA values. Maximal end-exercise ventilatory
equivalent (Vr/VQoK as well as the respiratory exchange ratio (R), were
not significantly different between the two conditions.
At a given submaximal work rate, a greater heart rate response occurred
during CO exposure. To minimize individual differences in both maximal
aerobic power and maximal heart rate, the data were reanalyzed, being
expressed as a percent of both the highest achieved ^02 and highest heart
rate in either the FA or CO condition. Exposure to CO increased the heart
rate significantly at any work rate from rest to 75% V02 max (Table 4).
-------
At 89% V02 max (highest common work rate for both the FA and CO conditions)
and at VCL max, no differences in heart rate between the FA and CO conditions
were found.
Examination of the ECG records during exercise and recovery showed no
occurrences of cardiac arrhythmias. No evidence of myocardial ischemia,
including J-point depression, was found.
Cardiac function appeared to be altered by low-level CO exposure.
Systolic time intervals were measured 3-4 minutes and 19-22 minutes after
the exhaustive exercise test in six subjects and are shown in Table 5.
Heart rates at these times were not statistically different between the FA
and CO conditions. During both CO and FA exposures at 4 minutes post
exercise, LVET was shortened relative to resting values. This LVET
shortening was significantly greater during the FA exposure than for the
CO conditon. Also, an impaired shortening of the electro-mechanical
systole (QS2) resulted, although no change in the pre-ejection period
(PEP) or the PEP/LVET ratio was found. These changes were not present
when STIs were measured at 20 minutes post-exercise.
Ventilatory responses to submaximal exercise during CO exposure were
also altered. Minute ventilation was significantly greater at 75% and
89% V0?, max (table 4). Both respiratory rate and tidal volume were
slightly but not significantly elevated during CO exposure. The anaerobic
threshold (20) occurred at a lower work rate during CO exposure than
during FA exposure, which resulted in the increased minute ventilation at
heavy work rates. During FA exposure, the anaerobic threshold was 50.7 +_ 2.6
tyO? max, whereas when breathing CO, the anaerobic threshold was reduced
to 46.0 +_ 2.2% tfO,, max. At work rates above the anaerobic threshold, the
venous lactate concentration was also increased significantly. Although
lactate levels were significantly higher during heavy exercise, maximal
post-exercise lactate levels were not significantly different between
the two conditions.
Oxygen debt during 60 minutes of recovery was not significantly
different between the FA and CO conditioning. Total oxygen consumed
above baseline oxygen uptake was 7.2 +_ 0.8 1 after FA exercise and 7.2 +_ 0.6
1 after CO exercise.
10
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Table 1. Initial Study--blood carboxyhemoglobin levels (% Sat)
Condition
Baseline
Resting after bolus
Light exercise
(2mph,0% grade)
Maximal Exercise
FA
1
1.05
+_.05
0.99
+ .06
1.02
+_.05
0.87
+ .07
FA
C.
1.08
^.08
1.11
+ .05
1.10
+ .04
1.02
+ .05
Average
FA
1.07a
+ .05
1.05b
+ .04
1.06d
+_.03
0.94f
+ .05
CO,
j.
1.03
+ .12
5.08
+ .32
4.80
+_.27
4.71
+ .25
C09
£.
0.96
+ .05
5.10
+ .19
4.91
+ .16
4.66
+ .23
Average
CO
0.99a
+ .05
5.09C
1-H
4.85e
+ .13
4.69g
+ .16
a FA and CO baseline HbCO values not significantly different.
FA resting and baseline HbCO values not significantly different.
c CO resting HbCO values greater than baseline value (P<.001).
FA light exercise and resting HbCO values not significantly different.
e CO light exercise HbCO values less than resting value (p<.01).
FA maximal exercise HbCO values less than resting or light exercise
value (p<.01).
9 CO maximal exercise HbCO values less than light exercise values
(p<.05) and resting values (p<.01).
11
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Table 2. Initial Study—changes in exercise performance
for 9 subjects (mean +_ SEM)
variable FA, FA2 Average CO, C02 Average
FA CO
Total Vertical Work 1.42 1.48 1.45 1.25 1.36 1.31a
(kpm x 104) +_.14 +.15 +_.14 +.12 +.13 +.12
Total Exercise Time 26.7 27.2 27.0 25.6 26.4 26.Oa
(min) +1.1 +1.1 +1.1 +1.0 +1.0 +1.0
18.2a
+1.1
42.6a
+2.0
Final Workrate
(kpm kg"1)
V0? max
-1 -1
(ml kg min )
18.6
+1.3
45.0
+2.3
19.8
+1.3
43.6
+2.2
19.2
+1.3
44.3
+2.2
17.8
+1.1
43.0
+2.1
18.6
+1.2
42.6
+2.0
Values for average CO performance less than FA performance (p<.05).
12
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Table 3. Initial Study—heart rate and ventilatory adaptations to maximal
aerobic work
Variable
Heart Rate (bpm)
V£ (1/min)
vT(D
fr(/min)
VV
R
FA1
192
±3
165
+10
2.87
+ .14
56.9
+2.2
48.0
+1.7
1.104
+ .010
FA2
192
+2
158
+10
2.85
+ .14
55.6
+2.2
48.5
+1.6
1.114
+ .023
Average
FA
192
+2
161
+9
2.86
+ .14
56.2
+2.1
48.2
+1.5
1.104
+ .012
co1
193
±3
158
+8
2.92
+ .12
54.0
+1.7
48.7
+1.6
1.081
+ .015
co2
191
+3
153
+10
2.87
+ .12
55.5
+2.2
49.1
+1.9
1.095
+ .019
Average
CO
192
±2
155
+8
2.90
+ .12
54.7
+1.8
48.9
+1.7
1.089
+ .013
13
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Table 4. Initial Study—effects of CO exposure during exercise (expressed
as a percent of the highest ^QO max) uP°n neart rate, ventilation,
and blood lactate (LA) (expressed as a percent of the maximal
value observed).
WORK RATE
35%
FA CO
Heart Rate 52.4% 53.2%a
+1.0 +0.8
V 21.4% 21.9?;
+0.5 ±0.5
VT 50.8% 51.3% 65.1% 65.2% 83.9% 84.3% 91.9% 93.5%
1 +2.9 +2.8 +2.9 +2.6 +2.0 +1.6 +0.6 +0.6
f 40.4% 41.0%a 46.9% 48.0%a 64.4% 66.8%a 79.1% 82.9%a
+1.5 +1.5 +1.7 +1.6 12.1 +1.9 +2.1 +1.7
LA 8.8% 9.0% 11.6% 12.7% 25.5% 29.5%b 43.9% 54.2%b
+0.7 +0.6 +0.7 +0.8 +1.5 +1.5 +3.2 +2.0
50%
FA
65
+_1
32
±0
.2%
.1
.0%
.7
CO
67.
+1.
32.
+0.
0%a
1
8%
9
FA
87.
+0.
57.
_tl.
75%
2%
9
1%
2
CO
89.
±0-
59.
+1.
3%a
9
l%b
1
FA
94
+0
79
+1
89%
.7%
.6
.0%
.7
CO
96
+0
83
+1
.3%a
.5
.9%b
.5
Main effect of CO greater than FA across all work rates (p<.05).
CO values greater than FA for this work rate (p<.05).
14
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Table 5. Initial Study—changes in electro-mechanical systole (QS^), left
ventricular ejection time (LVET), and the ratio of pre-ejection
period (PEP) to LVET (9 measurements in 6 subjects).
Heart Rate Q$2 (msec) LVET (msec) PEP/LVET
_FA CO FA CO FA CO FA CO
Pre-Exercise
3-4 minutes
Post-Exercise
19-20 minutes
Post-Exercise
61.1
+2.3
118.2
+3.0
95.4
+2.1
62.7
+2.5
120.2
+3.2
94.2
+1.8
398
+9
277
+12
358
+7
411
+7
309a
±6
365
+8
281
±9
193
±9
258
+4
292
±6
220a
+5
254
+3
0.42
+ .03
0.43
+ .04
0.39
+ .01
0.41
+ .02
0.41
+ .03
0.44
+ .02
aCO values significantly greater than FA values (p<.05).
15
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B. Dose-Response Study
HbCO changes during these experiments are shown in Table 6. The CO
bolus established levels of about 4, 6, and 9% HbCO compared to the FA
level of less than 1* HbCO. Maximal exercise reduced HbCO at 1-2 minutes
post-exercise by about O.lc, Hb when breathing FA and from 0.4% to 0.9% Hb
when exposed to CO.
Exercise performance progressively decreased as HbCO levels were
increased (Table 7). At the final workrate achieved, HbCO decreased 8.5,
16.4, and 18.5% when the initial CO exposure was 4%, 6%, and 9% HbCO,
respectively. Correspondingly, VQ max was decreased by 3.8, 8.3, and
11.156 at the levels of 45,, 6^-, and29^ HbCO, respectively.
During maximal aerobic work that occurred at lower final workrates
when breathing CO, maximal cardiac and ventilatory adaptations were about
the san-e (Table 8). As in the initial study, maximal heart rate and
maximal minute ventilation remained the same. No changes in end-exercise
tidal volume and respiratory rate were found. Both end-exercise ventilatory
equivalent (VE/VQ_) and respiratory exchange ratio (R) increased progressively
35 CO exposure increased.
As in the first study, examination of the EC6 records during exercise
and recovery revealed no occurrences of cardiac arrhythmias. Likewise,
no evidence of myocardial ischemia was found. No differences in systolic
time intervals were found before 4 min post maximal exercise in contrast
to our initial study (Table 9).
After 15 minutes of recovery no differences were seen in 02 debt
among any of the exposure conditions. Net oxygen uptake above baseline
oxygen uptake was 8.0 ± 0.2, 8.0 +. 0.3, 7.4 +_ 0.4, and 7.6 +_ 0.4 liters
for the 1%, 4%, 6i, and 9* HbCO conditions, respectively.
16
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Table 6. Dose-Response Study—blood carboxyhemoglobin levels (I- Sat).
Condition
Baseline
Resting after bolus
End-Exercise
a Baseline HbCO values not different from FA HbCO values.
Resting HbCO values greater than baseline values (p<0.01).
c End-Exercise HbCO values less than restina values after CO bolus (p<0.01)
FA
Y-h HbCO
0.85
+ .06
0.76
+ .05
0.67C
+ .05
4% HbCO
0.74a
+ .03
4.09b
+ .17
3.51C
+ .17
CO
6% HbCO
0.76a
+_.04
6.28b
+ .37
5.38°
+ .28
9% hbCO
0.82a
+ .05
9.51b
+_.22
8.71C
+ .15
17
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Table 7. Dose-Response Study—changes in exercise performance for
12 subjects (Mean + SEM).
Variable
Total Vertical Work
(kpm x 103)
Total Exercise Time
(min)
Final Workrate
(kpm kg-1 min~l )
FA
1% HbCO
6.48
+ .87
6.95
+ .42
18.81
+1.50
49.5
+2.1
4% HbCO
5.61a
+ .85
6.35a
+ .45
17.36a
+1.56
47. 6a
+1.8
CO
6% HbCO
4.89b
+ .72
5.81b
+ .41
15.76b
+1.53
45. 4b
+2.4
9% HbCO
4.63°
+ .62
5.67C
+ .31
15.40°
+1.22
44. Od
+1.6
_ _
(ml kg min )
aValues for 4% HbCO less than 1% HbCO (p<0.05).
bValues for 6% HbCO less than 3% HbCO (p<0.05) and 1% HbCO (p<0.01).
cValues for 9% HbCO less than 3% HbCO (p<0.05) and 1% HbCO (p<0.01).
Values for 9% HbCi
1% HbCO (p<0.01).
dValues for 9% HbCO less than 6% (p<0.05), 3% HbCO (p<0.01) and
18
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Table 8. Dose-Response Study--heart and ventilatory adaptations to maximal
aerobic work.
Condition
Heart Rate (bpm)
V£ (1/min)
VT(D
fr (min)
R
Fi 1 tered
air
187
+2
161
±5
2.77
+ .12
59.0
+1.8
43.0
+1.3
1.073
+ .014
4% HbCO
187
+2
160
+5
2.78
±•12
58.2
+2.0
44. 6a
+1.2
1.078
+ .018
CO
6% HbCO
187
±2
154
±6
2.72
±•10
57.0
+2.4
45. Oa
+1.6
1.106C
+ .023
9% HbCO
186
±2
157
+4
2.76
+ .12
57.8
+2.4
47. 5b
+1.6
1.114C
+ .019
Value is greater than FA (p=0.06).
b Value is greater than FA, 4%, and 6% HbCO (p<0.01).
c Value is greater than FA and 4% HbCO (p<0.05).
19
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Table 9. Dose-Response Study -- Changes in left ventricular ejection time (LVET), and the ratio
of pre-ejection period (PEP) to LVET in 10 subjects (Means +_ SEN).
ro
o
Pre-Exercise
4/minutes
Post-Exercise
15/minutes
Post-Exercise
fA
63
+4
114
±4
109
+3
Heart
4%
68
±4
119
±4
114
+5
Rate
6%
73
+4
116
+3
111
+3
LVET
9%
70
+5
121
+4
112
+5
£A
279
±8
201
+6
233
+7
4%
276
+7
192
+6
233
+7
6%
269
+7
194
±6
229
+7
9%
292
±11
191
+8
231
+7
FA
.380
+ .027
.270
+ .011
.379
+ .022
PEP/LVET
4%
.369
+ .031
.291
£.017
.399
+ .025
6%
.371
+ .027
.287
+ .011
.402
+ .023
9%
.362
+ .031
.273
+ .020
.374
+ .018
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SECTION VI
COMMENTS
At an altitude of 1610 m (Denver, Colorado), performance was reduced
as the HbCO level was increased. Compared to filtered air breathing
resulting with less than 1% HbCO, exposure to 3-10 % HbCO produced a
proportional decrease in total work done, total exercise time, and final
work rate achieved. At sea level using a similar stress test, Aronow and
Cassidy (3) found that raising the HbCO level from 1.07% to 3.95% in 45-55
year old asymptomatic subjects reduced the total exercise time by about
the same amount (5.0%). Horvath et al. (12) studied the effects of
increasing HbCO from 0.4% to 4.3% and found a decrease in the total
exercise time of 8.1% for a graded stress test. Therefore, CO exposure at
Denver's altitude resulted in a decrement in maximal exercise time similar
to but no greater than that found at sea.
Maximal aerobic work capacity was decreased in proportion to the
level of CO exposure. Figure 1 summarizes the decrement in Vn max found
2
in our study and reported by others who used similar exercise testing
during CO exposure from 3% to 21% HbCO (8,12,14,16,18,19). The decrement
for VQp max (i-e-> A^02 max) is nl9nly correlated (p< .01) to HbCO level
(A V()2 max = 1.08 x HbCO + 0.35) with an intercept that is close to zero
HbCO. The decrement in VQ^ roa* found at Denver altitude is similar to
that found at sea level and is clearly not greater than that observed at
sea level in normal subjects. Patients with chronic obstructive lung
disease also show a greater decrement in work performance at sea level
than normals (3), but any additional effect of altitude on work performance
with these patients has not been studied. Hypobaric hypoxia produced by
residing at altitudes higher than Denver does produce a significantly
greater reduction in VQ? max (5). Therefore, our observations do not
exclude the possibility that at higher altitude than Denver's, low-level
21
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25-1
20-
15-
GO
CO
09
10
• Sea level
x Denver
= 0.77+1.07X
r =0.96
5 10 15 20
HbCO (Sat.)
Figure 1. Effects of blood carboxyhemoglobin levels (HbCO) on
physical work capacity (tyQ max) in this altitude study (X)
and in others reported in the literature but done at sea
level.
22
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CO exposure may have additional detrimental effects on maximal aerobic
power compared to those found at 1600m altitude or below.
Although work capacity was reduced with CO exposure, certain
physiological variables observed during VQ? max work during the FA and CO
experiments were not significantly different. Maximal heart rate was
unaffected by CO in this study as has been reported in other studies done
at sea level (3,8,12). However, with higher HbCO levels at sea level
maximal heart rate was decreased (8,14,17,18,19). Maximal minute
ventilation (VF) (BTPS) was significantly greater at Denver altitude
than at sea level; however, VF max during CO exposure was slightly but not
significantly, lower than the FA VF max. This small change was also found
at sea level (8,12). Maximal ventilatory equivalent at 4-5 % HbCO was
unchanged as previously observed (8,12), but at 6% and 9% HbCO, the
maximal ventilatory equivalent and the respiratory exchange ratio increased
suggest CO provoked overventilation. Oxygen debt was unchanged confirming
an earlier report (12). Peak post-exercise venous lactates were the same
in both conditons which is in agreement with the findings of Ekblom and
Huot (8). Decreased post-exercise lactates have been reported by Horvath
et al. (12), but this may be explained by differences in test procedures,
subjects, or altitude conditions. These physiological adaptations to
maximal exercise were similar regardless of the gas breathed; however,
during CO breathing these adaptations to maximal work occurred at a
significantly lower work rate than during FA breathing. This difference
in maximal work rate suggests that CO exposure provokes a physiological
compensation such that greater cardio-respiratory adaptations tube place
at lower work rates during CO breathing.
Cardiac function appeared to be altered by low-level CO exposure.
Systolic time intervals were measured 3-4 minutes and 19-22 minutes
after the exhaustive exercise test. Heart rates at these times were not
statistically different between the FA and CO conditions. During FA
exposure in the inital study which used a long multistage exercise test,
left ventricular ejection time (LVET) was shortened relative to LVET at
rest, while the heart rate was elevated when measured in the supine position
at 4 minutes post-exercise. At this time, during CO exposure, LVET was
23
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significantly less shortened. A corresponding impaired shortening of the
electro-mechanical systolic (QS2) resulted, although no change in the pre-
ejection period (PEP) or the PEP/LVET ratio was found. These changes were
not present when STIs were measured at 20 minutes post-exercise. Also
these changes were not found after the dose-response study when a shorter,
supermaximal stress test was utilized, and measurements were taken in the
sitting position.
Following maximal exercise in healthy young men at sea level, LVET
was shortened to a similar extent whether subjects breathing CO or FA (1).
In the present study, LVET was not shortened as much during CO breathing.
A similar lack of LVET shortening at 4 min post-exercise has been reported
in patients having chest pain upon exertion (9,11,13,15).
In summary, low-level CO exposure resulting in a blood HbCO level of
3-9% HB at an altitude of 1610 m impaired work capacity and performance.
The impairments were of the same magnitude as those reported from sea
level studies.
24
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SECTION VII
REFERENCES
1. Anderson, E.W., J. Strauch, J. Knelson, and N. Fortuin. Effects of
carbon monoxide (CO) on exercise electrocardiogram and systolic time
intervals (STI). Circulation 48: Suppl II: 135, 1971.
2. Aranow, W.S., and J. Cassidy. Effect of carbon monoxide on maximal
treadmill exercise. A study in normal persons. Ann. Int. Med.
83: 496-499, 1975.
3. Aranow, W.S., J. Ferlinz, and F. Glauser. Effect of carbon monoxide
on exercise performance in chronic obstructive pulmonary disease.
Amer. J. Med. 63: 904-908, 1977.
4. Balke, B., and R.W. Ware. An expermental study of "physical fitness"
of Air Force personnel. U.S. Armed Forces Med. J. 10: 675-688, 1959.
5. Buskirk, E. Work and fatigue in high altitude. In: Physiology of
Work Capacity and Fatigue, edited by E. Simonson. Springfield, IL:
Charles C. Thomas, 1971, p. 312-322.
6. Dahms, T.E., and S.M. Horvath. Rapid, accurate technique for determina-
tion of carbon monoxide in blood. Clin. Chem. 20:533-537, 1974.
7. Dahms, T.E., S.M. Horvath, and D.J. Gray. Technique for accurately
producing desired carboxyhemoglobin levels during rest and exercise.
J. Appl. Physio!. 38: 366-368, 1975.
8. Ekblom, B., and R. Huot. Responses to submaximal and maximal exercise
at different levels of carboxyhemoglobin. Acta Physio!. Scand. 86:
474-482, 1972.
9. Gill.ilan, R.E., W.D. Parnes, B.E. Mondell, R.J. Bouchard, and J.R.
Warbasse. Systolic time intervals before and after maximal exercise
treadmill testing fcr evaluation of chest pain. Chest 71: 479-485,
1977.
10. Hartley, L.H. Effects of high-altitude environment on the cardiovascular
system of man. JAMA 215: 241-244, 1971.
11. Hoffman, A., M. Sefidpar, and D. Burckhardt. Systolische Zeitintervalle
in Ruhe und unter Belastung bei unterschiedlichem Schweregrad von
Linksherzinsuffizienze. Zeit. Kardiol. 63: 768-777, 1974.
25
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12. Horvath, S.M., P.B. Raven, I.E. Dahms, and D.J. Gray. Maximal
aerobic capacity at different levels of carboxyhemoglobin.
J. Appl. Physiol. 38: 300-303, 1975.
13. Lewis, R.P., D.G. Marsh, J.A. Sherman, W.F. Forester, and S.F. Schaar.
Enhanced diagnostic power of exercise testing for myocardial ischemia
by addition of postexercise left ventricular e.iection time.
Am. J. Cardiol. 39: 767-775,1977.
14. Pirnay, F., J. Dujardin, R. Deroanne, and J.M. Petit. Muscular
exercise during intoxication by carbon monoxide. J. Appl. Phvsiol.
31: 575-575, 1971.
15. Pouget, J.M., W.S. Harris, B.R. Mayron, and J.P. Naughton. Abnormal
responses of the systolic time intervals to exercise in patients with
angina pectoris. Circulation 43: 289-298, 1971.
16. Raven, P.B., B.L. Drinkwater, S.M. Horvath, R.O. Ruhlinq, J.A. Gliner,
J.C. Sutton, and N.W. Bolduan. Age, smoking habits, heat stress, and
their interactive effects with carbon monoxide and peroxyacetyl nitrate
on man's aerobic power. Int. J. Biometeor. 18: 222-232, 1974.
17. Raven, P.B., B.L. Drinkwater, R.O. Ruhling, N. Bolduan, S. Taguchi,
J. Gliner, and S.M. Horvath. Effect of carbon monoxide and peroxyacetyl
nitrate on man's maximal aerobic capacity. J. Appl. Physiol. 36:
288-293, 1974.
18. Vogel, J.A., and M.A. Gleser. Effect of carbon monoxide on oxygen
transport during exercise. J. Appl. Physiol. 32: 234-239, 1972.
19. Vogel, J.A., M.A. Gleser, R.C. Wheeler, and B.K. Whitten. Carbon
monoxide and physical work capacity. Arch. Environ. Health 24:
198-203, 1972.
20. Wasserman, K., B.J. Whipp, S.N. Koyal, and W.O. Beaver. Anaerobic
threshold and respiratory gas exchange during exercise. J. Appl.
Physiol. 35: 236-243, 1973.
21. Winer, B.J. Statistical Principles in Experimental Design (2nd. Ed.)
New York: McGraw-Hill, 1971.
26
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse befoic completing!
1 REPORT NO.
EPA-600/1-79-037
3. RECIPIENT'S ACCESSION NO.
4. TITLE AND SUBTITLE
LOW-LEVEL CARBON MONOXIDE EXPOSURE AND WORK
CAPACITY AT 1600 METERS
6. PERFORMING ORGANIZATION CODE
5. REPORT DATE
September 1973
7. AUTHOR(S)
Philip C. Weiser, Gerd J.A.
Thomas L. Kurt and David W.
8. PERFORMING ORGANIZATION REPORT NO.
Cropp, Call is
Dickey
G. Morrill
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Department of Physiology
National Asthma Center
1999 Julian Street
Denver, Colorado 80204
10. PROGRAM ELEMENT NO.
1AA817
11. CONTRACT/GRANT NO.
EPA 68-02-2244
12. SPONSORING AGENCY NAME AND ADDRESS
Health Effects Research Laboratory
Office of Research and Development
U.S. Environmental Protection Agency
Research Triangle Park, N.C. 27211
RTP, NC
13. TYPE OF REPORT AND PERIOD COVERED
14. SPONSORING AGENCY CODE
EPA 600/11
15. SUPPLEMENTARY NOTES
At sea level, low-level carbon monoxide (CO) exposure impairs exercise performance.
To determine if altitude residence at 1600 m augments this CO effect, two studies of
graded treadmill work capacity were done. The Initial Study investigated nine, non-
smoking, male subjects breathing either filtered air (FA) or 28 ppm CO in filtered air.
End-exercise carboxyhemoglobin (HbCO) levels averaged 0.9 ^HbCO breathing FA and
4.7 %HbCO breathing CO. Total work performance and aerobic work capacity were reduced.
Work heart rate was elevated, and post-exercise left ventricular ejection time breathim
CO did not shorten to the same degree as with FA exposure. CO exposure resulted in a
lower anaerobic threshold, and a greater minute ventilation occurred at work rates
heavier than the anaerobic threshold due to an increased blood lactate level. The
Dose-Response Study exposed twelve subjects to FA or -CO such that the end-exercise HbCO
levels were 0.7, 3.5, 5.4 and 8.7 %HbCO. Exercise performance and aerobic work capa-
city were impaired in proportion to the CO exposure. In both studies, maximal cardio-
pulmonary responses were not different, but submaximal exercise changes were elevated
breathing CO. Thus, in healthy young men residing near 1600 m, an increase in low-
level CO exposure produced a linear decrement in maximal aerobic performance similar
to that reported at sea level.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COS AT I Field/Group
Air Pollution
Carbon Monoxide
Physiological Effects
Exercise
06F
18. DISTRIBUTION STATEMENT
Release to Public
19. SECURITY CLASS (This Report)
Unclassified
21. NO. OF PAGES
35
20. SECURITY CLASS (Thispage)
UnclassifiPfl
22. PRICE
EPA Form 2220—1 (Rev. 4-77) PREVIOUS EDITION is OBSOLETE
27
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