EPA-RI-72-002
July 1972                  Environmental Health Effects Research
Physiological Adaptations
to  Carbon  Monoxide Levels
and Exercise in  Normal Men
                             Office of Research and Monitoring
                             U.S.  Environmental Protection Agency
                             Washington, D.C. 20460

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                                           EPA-RI-72-002
  Physiological Adaptations

 to  Carbon Monoxide Levels

and  Exercise  in Normal Men
                        by
             C. R. Collier, J. M. Workman
         J. G. Mohler, J. Aaronson, and 0. Cabula

            University of Southern California
               Department of Medicine
                 2025 Zonal Avenue
            Los Angeles, California 90033
              Contract No.  68-02-0334
             Program Element No.  1A1007
           Project Officer:  Dr. John H. Knelson

          Division of Health Effects Research
         National Environmental  Research Center
       Research Triangle Park, North Carolina 27711
                   Prepared for

          OFFICE OF RESEARCH AND MONITORING
          U.S. ENVIRONMENTAL PROTECTION AGENCY
               WASHINGTON, D. C. 20460
                          !

                    July 1972

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                                          EPA REVIEW NOTICE



               This report has been reviewed by the Environmental Protection Agency

               and approved for publication.  Approval does not signify that the

               contents necessarily reflect the views and policies of the Agency,

               nor d.oes mention of trade names or commercial products constitute

               endorsement or recommendation for use.
                                                 11
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                                SUMMARY









     Normal, young, non-smoking men were studied at rest and during




submaximal exercise with carboxyhemoglobin (COHb) levels of about




1% and after breathing CO to raise the COHb level to 8 to 9%.




Arterial and mixed venous blood was sampled.  CO caused an increase




in minute volume and breathing frequency during exercise but not at




rest.  CO caused no changes in cardiac output, heart rate, lactate,




lactate/pyruvate ratio, tidal volume, C0~ output or 2,3 DPG during




rest or exercise.  CO caused a decrease in $2 consumption, in




arterial-venous Q  content difference and in venous 0,, content and




venous Po™ during exercise and in the latter two also at rest.




Changes in On affinity are still being calculated.
                                  -1-

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INTRODUCTION





     Carbon monoxide is believed to exert its toxic effect almost entirely



through its binding on the active sites of hemoglobin.  This reduces the



oxygen carrying capacity of hemoglobin and produces a hypoxemia similar



to that of anemia.  However, the displacement of oxygen from active



sites has the equivalent effect of displacing the oxygen dissociation



curve of the remaining sites to the left and hence effectively increasing



the affinity of the remaining sites for oxygen.   This effect has long



been known since Haldane .  This phenomenon has  little effect on



arterial oxygenation but has been believed to have a profound effect on



oxygenation of tissue and on oxygenation of venous blood.  Because of  .



normal arterial Po_ in CO poisoning, it is generally believed that the



body has limited physiological defense against CO compared with the



hypoxemia of altitude.



     Of the many studies on the effects of carbon monoxide, only


            234
Ayres, et al ' '  have directly sampled the blood from the pulmonary



arteries.  In his studies, observations were made only at rest.  In the



studies of Vogel, et al ' /observations were made at submaximal and



maximal exercise.  The cardiac output was measured by dye dilution, but a



mixed venous sample was not obtained.



     This study reports observations made on healthy, young, normal, male



subjects under conditions of rest and submaximal work before and after



giving a load of carbon monoxide to produce approximately 10% carboxy-



hemoglobin concentration.  Pulmonary artery blood was sampled.



Observations were also done on levels of 2,3 diphosphoglycerate and



estimations were made of the oxygen affinity of the hemoglobin, both in



vitro and in vivo.
                                  -2-

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METHODS





     Nine, young, male, non-smoking subjects were chosen for study.  The



physical characteristics of the last seven subjects are shown in Table I.



The first two subjects served mainly as pilot studies.  A number of



pieces of information are missing about both of these.  Essentially all



of the data desired is available on the last seven subjects, except that



one sample of blood from the pulmonary artery was actually a wedge sample



and was omitted from the data.



     The subjects ate a light breakfast before 6 a.m. and reported to the



laboratory about 7 a.m.  Blood carboxyhemoglobin was estimated by a method



modified slightly from Jones, et al .   The subject warmed up for 10



minutes on the stationary constant load bicycle ergometer at a work load



of 50% of his estimated maximal 0  consumption (Vo~ max).  The predicted

                                                                   0

V02 max. as calculated according to the formula of Armstrong, et al



based on age and body weight and the corresponding bicycle load was



calculated from the empirical formula:



     L = 570 Vo  - 200



     where L = bicycle load in KPM

     •

     Vo_ = desired 0  consumption in L/min.


                                               9
The subject then lay on a bed while a Swan-Ganz^ catheter was inserted in an



antecubital vein in one arm and advanced to the pulmonary artery.  A



plastic arterial cannula was placed percutaneously in a brachial artery



of the other arm.  The subject then moved to the bicycle where he



remained for the rest of the experiment.  After moving, the position of



the catheter tip was rechecked.  Observations of inspired minute volume



and of heart rate were made during a rest period of five minutes, the



last three minutes of which samples of expired air, arterial blood and



mixed venous blood were obtained.  Exercise was then performed at a load
                                  —3—

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of 75% of the estimated Vo« max. for a period of 5 minutes.  Heart rate,

EGG, respiratory rate and inspired minute volume was observed for the

entire period.  Mixed venous and arterial blood samples were obtained

during the last two minutes of exercise and expired air was collected

for the last minute of exercise.

     The subjects were then loaded with carbon monoxide, first to about

7% carboxyhemoglobin, and then to 10% carboxyhemoglobin by breathing a

measured volume of 1% carbon monoxide in air.  The dose was calculated

according to the formula of Pitts and Pace^.  After a period of from

20 to 45 minutes, the studies at rest and exercise were repeated as

described for control state.  During the exercise period, the subject

breathed air containing 60-70 ppm CO.  Following the second exercise

study the catheter was withdrawn and the subject breathed 100% oxygen

for approximately 30 minutes.  A few of the subjects experienced a mild

phlebitis and thrombosis in the vein the cardiac catheter had been

placed in.  All the subjects were able to complete the protocol except

one, K.S., who passed out and would have fallen from the bicycle after

4 minutes and 40 seconds of exercise.  The subjects knew the protocol.

Several of them stated that the second exercise period was easier than

the first.

     Blood samples were measured for pH, Po2 and Pco2 using radiometer

electrodes and Model PHM72 readout system.   Expired air volume was

measured in a large spirometer and a sample taken for analysis by the

micro-Scholander method.  Blood was analyzed for 0 , C02 and CO content

by the method of Van Slyke.  Hemoglobin concentration was measured as

cyanmethemoglobin photometrically.  Lactate and pyruvate were 2,3

diphosphoglycerate was determined by specific enzymatic methods using

commercial kits.*
                                  _4_       .

* Lactate and pyruvate were determined by use of kits from Boehringer
  Mannheim and 2,3 DPG by using  a kit from  Calbiochem.

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     Blood was equilibrated in a swirl tonometer with approximately 3%


and 4% oxygen" and; 5%  CG-- in- nitrogen /'respectively;^ 'aM'? oxygen1' c'onteh't , t °


          and pH were determined1 as"1 described 'above.  Th'e cardiac output
was calculated from  the  Pick' equation and in' vitro andt 'in? vivo ••pnn \ will


be computed from the data  of the mixed < venous'* sample by methods to be


developed.  The difference between means of -. control and after CO was  '


tested for statistical significance by student's "t" test- for paired


data..


     The base excess of  the extracellular fluid was computed according


to Collier, Hackney  and  Mohler V".



RESULTS




     Table II contains a summary of the  most- pertinent data; obtained;.  The


mean and standard deviation, is  shown for all' data obtained1. ; The! mean r


carboxyhemoglobin concentration was 8.9% -after, loading: iahd duringcn: •.


exercise this lowered slightly  to 7.8% even though: 60. to 70.ppin of


carbon monoxide was  breathed during the  exercise period.:  .There-.wasn a;.r:i ;


significant increase in  minute  volume during- exercise after*' CO. IcThds.was


due entirely to an increase in  respiratory frequency: as ;the; tidalh .volume


did not change significantly.   The increase in minute volume during


exercise caused a islight lowering pf: -the arterial. P.co A, -,. but -the-. Change


was not statistically significant.  There were no significant changes in


arterial Pco^ caused by  carbon  monoxide'.  However ,.•> the mixed; venous POA


was significantly lowered  at both rest and' during exercise ,-ibeingr lowered


to 22.2 torr during  exercise after CO. ; .The lowest mixed;; yenous. Pdo i l<


observed was 20 torr on  two occasions.  The] alveolar rarte'rtlal - oxygen


tension dif f erence :was Increased; during) bothvresti and- exercise.cli.The
             t

difference was not significant  during exercise but was during rest.   This

                     f>
may have been due to observation during  an unsteady state from the previous


exercise.

                                   -5-

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     The arterial oxygen content was, of course, lowered as this was




essentially a manipulated variable.  The mixed venous oxygen content,




however, was also significantly reduced, being approximately 1 volume %




lower than the control.  However, the arterial-venous oxygen content




difference was also lowered by CO during both rest and exercise.  The




change caused by CO was not statistically significant at rest but was




statistically significant during exercise.   This was made possible not




by a change in blood flow which did not change significantly due to CO




during either rest or exercise but was caused by a reduction in oxygen




consumption during exercise.  There were no statistically significant




changes in C02 output but there was slight drop after CO during




exercise so the respiratory exchange ratio was essentially unchanged.




There were no significant changes in lactate, pyruvate, or lactate/




pyruvate ratios caused by CO during exercise.  The changes observed




after CO at rest were probably related to the first exercise period.




There were no significant changes in DPG caused by either CO or exercise.




     Table III shows the results of some of the most pertinent acid-base




data for arterial and venous blood.  The lactate values are again shown




in this table but in meq./L, for comparison with the acid-base data.




Fig. 1 shows the arterial and venous acid-base measurements at rest and




during exercise.






DISCUSSION






     The reduction in oxygen consumption which was observed after CO



during exercise was also observed during maximal 3 minute exercise in an



                               12
earlier study in our laboratory   but not observed during submaximal 3




minute exercise.  It may be that some of our subjects were close to Vo« max.
                                  -6-

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One of our subjects, K.S., exercised at Vo2 max. because he was unable to




complete the work.  Our empiric formula for computing the bicycle load




may have given too high a work load.  In comparison with the formula of




Cotes  , our subjects were working at about 84% of Vo2 max. and if




compared with Astrand and Rodahl   were working at 87% of Vo^ max., rather




than at the expected 75%.  This reduction in oxygen consumption which is




observed after CO during exercise seems tenable only if we assume that




there is an increase in oxygen debt because it does not seem logical




that carbon monoxide would cause an increase in mechanical efficiency.




However, this could not be absolutely ruled out without further study.




     A reduction in oxygen consumption after CO was also reported by




Chevalier, et al  .  The total amount of oxygen consumed before CO for




5 minutes of exercise was 5.99 L. (an average of 10 subjects) and after




CO the same workload  required only an extra 5.79 L.  This difference




was not significant but neither was the oxygen debt which was 1.65 L.




control and 1.84 L. after CO.  However, the percentage of the oxygen debt




of the total, or the sum of these two was significant at the 5% level.




The sum of 02 consumed during work plus the 02 debt is identical before




and after CO.




     Three other studies do not report a change in oxygen consumption




during exercise.  Asmussen and Chiodi  , reporting on 3 subjects, and




Klausen, et al^ , reporting on 8 subjects, both showed no difference in




oxygen consumption.  Vogel, et al  reported that there was no difference




in oxygen consumption at the same work load and shows a graph on which




oxygen consumption is plotted against work load for a number of




individuals.  In view of our data, it might be well to look at the




individual cases in his study.
                                   -7-

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     The cardiac output which we found unchanged was also reported
unchanged by Asmussen and Chiodi   and by Klausen, et al  .   However,
in their studies the cardiac output was measured by an indirect
"bloodless" method.  The acetylene method was used by the first group
and a CCL rebreathing method by the second.  Vogel, et al ,using the
dye-dilution method, report that there is an increase in cardiac output
for  suhnaximal exercise.  However, in Vogel's presentation, he
plotted the cardiac output as a function of oxygen consumption rather
than as workload.   If there were small reductions in oxygen consumption
at the same workload, this might change the data somewhat.  Vogel's
subjects were at a higher COHb (about 20%) and the difference in response
of cardiac output probably represents a true difference in response at
                                  18
the higher CO load.  Chiodi, et al   found an increase in cardiac output
at high CO levels but no increase at lower CO levels.
     The dye-dilution method which Vogel used gives approximately the
same value for cardiac output as the direct Pick method in patients at
                            19
rest or during .mild exercise   but has not been adequately compared at
                                                              20
high workloads  in normals.  The normal data of Tabakin, et  al   using
dye dilution and treadmill exercise gives higher cardiac outputs at a
                                              21
given work load than the data of Reeves, et al   using the direct Fick.
Our subjects show only slightly higher cardiac outputs than  those of
Reeves.  Even though the direct Fick method may be preferable to the dye-
dilution method at heavy exercise, the difference in methods probably
does not account for the difference in response of cardiac output to CO
in our two studies.
     The heart rate which we found unchanged was found to be increased by
most other observers '  '  '  '     However, Chevalier, et al   report a
                                  -8-

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reduction in heart rate during exercise following CO inhalation.  Another




study in our laboratory   also showed no change in heart rate after CO.




In our first study, the subjects were sham loaded in a single blind




procedure; but in the present study, the subjects knew that the CO load




followed the control study.  The ECG showed no changes after CO at rest



                                                                         22
or exercise.  This was also found in the young subjects of Fortuin, et al




     The alveolar-arterial Po  difference was quite high in all of our




subjects, perhaps because they tended to hyperventilate.  CO caused an




increase in this difference which was statistically significant at rest.


                23
Brody and Coburn   first reported this phenomenon which is due to the




decrease in mixed venous Po~ and 0» content after CO.




     The acid-base data given in Table III shows that the acid-base




changes are mostly due to lactate production during exercise.  Neither




lactate production nor acid-base changes are affected by the CO load.




The lactate concentration at rest after CO was elevated but this is




probably because the resting sample after CO was taken from 38 to 73 min.




(average 59 min.) after the first exercise and the lactate had not yet




been metabolized to control values.  Asmussen and Chiodi   reported an




increase in lactate production during exercise caused by CO but their




COHb levels were 20-30%.


                  n i

     Visser, et al   have investigated the relation between lactate and




arterial blood acid-base changes following acute exercise and found




that the change in blood lactate was almost identical with the change




in plasma bicarbonate concentration corrected for changes in Pco?.




(This change is essentially the change in base excess of the arterial




plasma (BEp).) The addition of lactic acid to in vitro blood gives a




lesser change in BEp, making it necessary to postulate some unknown




acids in the body.  -There are two errors in this analysis which have been
                                 -9-

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clarified by more recent work.  First, the correction for changes in Pco-



was based on an in vitro CCL dissociation slope for blood.  Because of



dilution effective of the buffer value of blood with interstitial fluid,



the ECF has a buffer value which is about 1/3 of that of blood.  Thus



if there was a change in Pco~ during exercise in his patient population,



Visser would have calculated a false change in base.  We have obviated



this by calculating the base excess of the ECF  .   Second, inspection of



figure 1 shows that the exchange of CO  from venous to arterial blood is



along an in vitro blood slope and not along the ECF or in vivo slope.



This is due to the fact that the pulmonary capillary exchange is only



with the blood and does not include an appreciable interstitial fluid


                                                             ? c
pool.  This relationship  was first stated by Roos and Thomas  . 'This



fact makes it necessary to use the mixed venous blood for such comparison.



Arterial blood can be used only if the A-V LHCO'j  difference is constant



in the two situations.  This is certainly not true when comparing rest



and exercise.  Figure 1 and Table IV show  the much greater change in



base excess of arterial blood than of mixed venous blood.  The close



equimolecular correlation of lactate and base deficit is only fortuitous



and has no scientific basis.  There seems to be no need in searching for



other sources of acid.
                                 -10-

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                              REFERENCES
1.   Haldane, J.B.S.:  "The Dissociation of Oxyhemoglobin in Human Blood
     During Partial CO Poisoning".  J. Physiol. 45: XXII-XXIV, 1912-1913.

2.   Ayres, S. M., Gianelli, S., Jr. and Armstrong, R. G.:
     "Carboxyhemoglobin:  Hemodynamic and Respiratory Responses to Small
     Concentrations".  Science 149:  193-194, 1965.

3.   Ayres, S. M., Mueller, H. S., Gregory, J. J. , Gianelli, S., Jr. and
     Penny, J. L.:  "Systemic and Myocardial Hemodynamic Responses to
     Relatively Small Concentrations of Carboxyhemoglobin (COHb)".
     Arch. Environ. Health  18:  699-709, 1969.

4.   Ayres, S. M., Gianelli, S., Jr. and Mueller, H.:   "Myocardial and
     Systemic Responses to Carboxyhemoglobin".  Ann. N.Y. Acad. Sci.
     174:  268-293, 1970.

5.   Vogel, J. A., Gleser, M. A., Wheeler, R. C. and Whitten, B. K.:
     "Carbon Monoxide and Physical Work Capacity".  Arch. Environ.
     Health  24:  198-203, 1972.

6.   Vogel, J. A., Gleser, M. A. and Mello, R. P.:  "Oxygen Transport
     during Exercise with Carbon Monoxide Exposure".  Fed. Proc. 30:
     371, 1971.

7.   Jones, R. H., Ellicott, M. F., Cadigan, J. B. and Gaensler, E. A.:
     "The Relationship between Alveolar and Blood Carbon Monoxide
     Concentrations during Breathholding".  J. Lab. Clin. Med. 51:
     553-564, 1958.

8.   Armstrong, B. W., Workman, J. N., Hunt, H. H., Jr. and Roemich, W. R.:
     "Clinico-Physiologic Evaluation of Physical Working Capacity in
     Persons with Pulmonary Disease".  Amer. Rev. Resp. Dis. 93:  90-99,
     1966.

9.   Swan, H. J. C., Ganz, W., Forrester, J., Marcus,  H., Diamond, G. and
     Chonette, D.:  "Catheterization of the Heart in Man with Use of a
     Flow-Directed Balloon-Tipped Catheter".  N. Engl. J. Med.  283:
     447-451, 1970.

10.  Pitts, G. C. and Pace, N.:  "The Effect of Blood Carboxyhemoglobin
     Concentration on Hypoxia Tolerance".  Am. J. Physiol.  148:  139-151,
     1947.

11.  Collier, C. R., Hackney, J. D. and Mohler, J. G.:  "Use of Extra-
     cellular Base Excess in Diagnosis of Acid-Base Disorders:  A
     Conceptual Approach".  Chest 6: Supplement 6S-12S, 1972.

12.  Workman, J. M. and Collier, C. R.:  "Effects of  Carbon Monoxide on
     Human Physical Performance".  Report on Contract CPA 70-99 performed
     for Environmental Protection Agency, Durham, N.C.
                                 -11-

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13.  Cotes, J. E.:  "Lung Function".  2nd edition, pp. 312-315, F. A. Davis,
     Philadelphia, 1968.

14.  Astrand, P. 0. and Rodahl, K.:  "Textbook of Work Physiology",  p.  615,
     McGraw-Hill, New York, 1970.

15.  Chevalier, R. B., Krumholz, R. A. and Ross, J. C.:   "Reaction of
     Nonsmokers to Carbon Monoxide Inhalation".  J.A.M.A.   198:  1061-
     1064, 1966.

16.  Asmussen, E. and Chiodi, H.:  "The Effect of Hypoxemia on Ventilation
     and Circulation in Man".  Am. J. Physiol.  132: 426-436, 1941.

17.  Klausen, K., Rosmussen, B., Gjellerod, H., Madsen, H.  and Petersen, E.:
     "Circulation, Metabolism and Ventilation during Prolonged Exposure
     to Carbon Monoxide and to High Altitude".  Scand. J. Clin. Lab. Invest.
     Suppl.  103:  26-38, 1968.

18.  Chiodi, H., Dill, D. B., Consolazio, F. and Horvath, S. M.:
     "Respiratory and Circulatory Responses to Acute Carbon Monoxide
     Poisoning".  Am. J. Physiol. 134:  683-693, 1941.

19.  Eliasch, H., Lager.lbf, H., Bucht, H., Ek, J., Eriksson, K. , Bergstrb'm, J
     and Werko, L.:  "Comparison of the Dye Dilution and  the Direct Pick
     Methods for the Measurement of Cardiac Output in Man".  Scand. J.
     Clin. Lab. Invest. Suppl. 20:  73-78, 1955.

20.  Tabakin, B. S.,  Hanson, J. S., Merriam, T. W., jr.,  and Caldwell, E. J.:
     "Hemodynamic Response of Normal Men to Graded Treadmill Exercise".
     J. Appl. Physiol.  19:  457-464, 1964.

21.  Reeves, J. T., Grover, R. F., Blount, S. G., Jr. and Filley, G. F.:
     "Cardiac Output Response to Standing and Treadmill Walking".
     J. Appl. Physiol.  16: 283-288, 1961.

22.  Fortuin, N. J.,  Anderson, E. W., Strauch, J. M. and  Knelson, J. H.:
     "Cardiovascular Effects of Exposure to Low Levels of Carbon Monoxide
     in Man".  Unpublished paper.

23.  Brody, J. S. and Coburn, R. F.:  "Carbon Monoxide-Induced Arterial
     Hypoxemia".  Science 164:  1297-1298, 1969.

24.  Visser, B. F., Kreukniet, J. and Maas, A. H.:  "Increase of Whole
     Blood Lactic Acid Concentration during Exercise as Predicted from pH
     and Pco2 Determinations".  Pfliig.  Arch, ges. Physiol.  281:  300-304,
     1964.

25.  Roos,   A. and Thomas, L. J., Jr.:   "The In-vitro and In-vivo Carbon
     Dioxide Dissociation Curves of True Plasma".  Anesthesiology  28:
     1048-1063, 1967.
                                 -12-

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Table I  VITAL DATA ON SUBJECTS STUDIED
Subject

AR
SG
RA .
KS
JB
JS
VS
Age
yr.
34
22
27
23
30
19
21
Weight
kg.
81.6
75.7
70.3
72.6
68.0
66.7
96.8
Height
on.
170
169
179
183
175
170
189
Body Surfai
M2
1.93
1.86
1.88
1.94
1.83
1.77
2.24
                 -13-

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Table II  MEASURED AND COMPUTED DATA
COHb
*E
f
VT
Paco2
Pao2
A-a Do2
Pv-o2
L Ca°2
^^
Cvo-
Cao2-Cvb2
yo2
Q
fH
Vco2
R
Lactate
Pyruvate
Lact./pyr. ratio
2,3 DPG
Units
L/min
/min
L
torr
torr
torr
torr
vol %
vol %
vol %
L/min
L/min
/min
L/min

mg %
mg %

trg/gm,

R
Control
Mean
1.1
12.9
13.5
0.97
34.0
86.3
23.4
35.9
18.9
12.9
5.9
0.35
6.0
81
0.32
0.90
18.9
0.92
30.0
, Hb 11.7
S.D.
0.6
4.7
3.9
0.29
5.7
8.0
5.4
1.7
1.2
1.3
1.0
0.06
0.9
13
0.09
0.15
5.7
0.95
13.5
3.1
E S T
E X E R C I S
After CO
Mean
8.9
15.2
17.0
0.98
32.0
85.3
26.0
31.4
17.4
11.9
5.5
0.38
7.2
104
0.34
0.90
30.4
1.60
32.5
12.7
S.D.
1.7
4.9
5.8
0.46
6.5
8.3
6.2
2.2
0.9
1.6
1.2
0.07
1.9
15
0.09
0.17
12.6
1.33
31.5
3.8
P
N.S.
N.S.
N.S.
N.S.
N.S.
<0.05
<0.01
-
<0.1
N.S.
N.S.
N S.

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           Table III  ACID-BASE AND LACTATL  DATA
REST
EXERCISE
Units
Arterial
Pco_ torr
PH
(.HCOo J meq./L
BE£CF meq./L
Mixed Venous
Pco- torr
pH
1 HCO« J meq./L
BE meq . / L
ECF
Lactate meq./L
Control
Mean
34.0
7.43
22.3
-1.5

40.6
7.40
24.6
0.4
2.1
S.D.
5.7
0.04
1.9
1.7

5.1
0.03
1.7
1.6
0.6
After
Mean
32.0
7.43
20.6
-3.2

38.4
7.39
22.6
-1.5
3.4
CO
S.D.
6.5
0.07
1.3
1.0

5.2
0.05
1.3
1.3
1.4
Control
P
N.S.
N.S.
<0.02
<0.02

N.S.
N.S.
<0.02
<0.02
<0.02
Mean
31
7
15
-9

57
7
21
-5
10
.0
.31
.3
.8

.9
.19
.3
.2
.3
S.D.
2.5
0.04
2.1
2.3

4.6
0.05
1.3
1.8
1.8
After CO
Mean
29.4
7.31
14.7
-10.4

55.0
7.18
20.0
-6.7
10.3
S.D.
3.5
0.02
1.1
1.2

4.7
0.03
1.4
1.3
1.9
P
N.S.
, N.S.
N.S.
N.S.

N.S.
N.S.
N.S.
<0.05
N.S.

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  Table IV  CHANGES  IN  ACID-BASE AND LACTATE PRODUCED BY EXERCISE
                             Control                    After  CO
                        (Exercise - Rest)           (Exercise  - Rest)
                             meq./L,                      meq./L


A Laotate                     +8.2                        +6.9
'. BE    Venous                -5.6                         •*>•-•
    ECF


        Arterial              -fi-3                        ~7-?

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 meq./L.
30
20
10
   7.0
7.2
7.4
                            Pco2 s 4O
7.6
                                           ECF

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                                 LEGENDS





Table I                  Vital data on subjects studied





Table II                 Measured and computed data



     COHb                % saturation of Hb with CO



     Vp                  Expired minute volume



     fR                  Respiratory frequency



     V                   Tidal volume
                                                \

     Paco_               Arterial Pco-



     Pao2                Arterial Po-



     Pvo9                Mixed venous Po«



     A-a Do2             Alveolar-arterial Po_ difference



     Qs/Qt               Total effective R to L shunt as % of total blood

                         flow



     Cao2                Arterial CL content



     Cvoo                Mixed venous Qj content



     Vo7                 0  consumption



     Q                   Cardiac output



     f                   Heart rate
      H


     Vco                 C02 output



     R                   Respiratory exchange ratio



     2,3 DPG             2,3 Diphosphoglycerate concentration



     S.D.                Standard deviation



     P                   Probability that  the difference between  the  means

                         before  and after  CO  is due  to  chance



     N.S.                No statistically  significant difference





Table III                Acid-Base and  Lactate  Data



     T HCO-T ;             Calculated concentration  of bicarbonate  in  the
          3 - p
                         plasma



      BE                  Base  excess of  extracellular fluid
       ECF

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Table IV                 Changes in Acid-Base and Lactate Produced by
                         Exercise
                         (Differences between average data of Table III)


Figure 1                 Average acid-base data for rest and exercise
                         before CO

     v                   Mixed venous blood

     a                   Arterial blood

     ECF                 Average normal non-bicarbonate buffer line for
                         extracellular fluid in humans

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