Clinical Science and Molecular Medicine (1976) 51, 335-344.
Gas exchange during exercise in healthy people II. Venous admixture
E. A. HARRIS, EVE R. SEELYE
AND
R. M. L. WHITLOCK
CIinical Physiology Department, Green Lane Hospital, Auckland, New Zealand
(Receiued 14 July 1975)
Key words: alveolar and airway closure, exercise, venous shunt.
SummarY 1. Venous admixturelcardiac output ratio (Ova/
e t ) has been measured in twenty-four healthy volunteer subjects of both sexes aged 20-71 years, at rest and during the steady state of treadmill exercise at two rates of work, and breathing air and breathing oxygen. 2. With oxygen breathing, Ovalet was considerably less during exercise than during the time subjects were taking either normal or deep breaths of oxygen at rest, and did not significantlyincreasewith the intensity of exercise. It is postulated that the increase in ventilation during exercise opens most or all of those alveoli which, during oxygen breathing at rest, close because of critically low ventilation/ perfusion (V/Q>ratios. 3. With air breathing, Ovalet fell from rest to exercise (especially in older subjects), presumably due to improved ventilation of alveoli at the lung bases. With an increase in work rate e v a / e t increased in all age groups. This increase was not due to increase in the shunt fraction (e,/et), nor to limitation of diffusing capacity; it arose from an increase in V/Q variance. 4. Equations have been derived for the prediction of normal e v a / e t during exercise, with or without correction for the effects of increasing pulmonary capillary temperature. These effects do not materially influence the accuracy of prediction, but may be relevant to some of the interpretations. In particular, they provide a further indication that es/(& probably cannot be measured by breathing oxygen at rest, even in deep breathing. Correspondence: Dr E. A. Harris, Clinical Physiology Department, Green Lane Hospital, Auckland, New Zealand.
335
Introduction
The effects of different alveolar oxygen tensions (PA,o~)on alveolar-to-arterial oxygen-tension gradient (PA,O~ -Pa,o,) and venous admixturelcardiac output ratio (eva/et) were studied in forty-eight healthy men and women, ages 20-74 years, by Harris, Kenyon, Nisbet, Seelye & Whitlock (1974). These data provided prediction standards for normal Ova/ e t . The reduction in e v a / e t when deep, as contrasted with ordinary, breaths of oxygen were taken led to speculation as to whether ‘deep-breathreversible’ shunt might make a significant contribution to venous admixture when air was breathed, diminishing the importance of pulmonary ventilationlperfusion (310)variance. Subsequent papers by Wagner, Laravuso, Uhl & West (1974) and by Dantzker, Wagner & West (1975) point to a different interpretation, based on the selective instability of lung units with low V / eratios during oxygen breathing. This paper presents the results of studies in twentyfour healthy subjects at rest and during exercise. The objects were (1) to add to available information about the normal range of venous admixture during exercise, (2) to interpret the data in the light of the work of Wagner et al. (1974) and Dantzker et al. (1975) and (3) to assess the effect on h a l e t of correcting blood-gas tensions to pulmonary capillary temperature; in the preceding paper Bradley, Harris, Seelye & Whitlock (1976) have shown that such
336
E. A . Harris, Eve R. Seelye and R. M. L. Whirlock
where Voz was the measured Oz uptake (ml/min) during the particular exercise breathing air. Eqn. (4) was calculated from the pooled data of Epstein, Beiser, Stampfer, Robinson & Braunwald (1 967), Hermansen, Ekblom & Saltin (1970) and Levy, Methods Tabakin & Hanson (1961), who measured cardiac Subjects, procedure and laboratory methods output at various rates of work in the upright position, in healthy subjects. We were unable to find These, including details of the subject groups A, B sufficiently detailed information to warrant making and C, have been described in the preceding paper a distinction according to age. (Bradley et al., 1976). Error in the assumption of arteriovenous Oz difference affects the calculated ovalot less during exercise than at rest. For example, an error of 10 Calculations ml/l would have caused an error (in the opposite For a subject breathing air, alveolar Poz (PA,oz) sense) in ova/@ of 0.3, 0.8 and 1.0% in groups A, was calculated from the alveolar gas equation (1). B and C respectively at rest. During exercise, however, the error would have been only about 0.2% in P A , o ~= P,,oz -Pa,coz[Fr,oz +(1 -Fr,oz)/R1 (1) all age groups. Moreover, the interpretations in the where R is the exchange ratio calculated from expireddiscussion are based on mean values from groups of was calculated gas analysis. With Oz breathing, PA,o~ eight subjects, and the above errors would correspond as shown in eqn. (2). to an individual error of 28.3 ml/l (10 x J8)in arteriovenous difference. It is unlikely that the assumptions PA,o~ = 0.9972 (PB- 6.27) -Pa,coz (2) erred by more than this, and at rest especially the During the course of the experiments the mean FOZ error was almost certainly less. of the oxygen supply was found to be 0.9972, SD Two sets of values of P ~ , o ~ - P a , and o ~ ovalet 0.0050. Some of the variation was due to error of were calculated in each case,according to different measurement but sometimes, as confirmed by the reference temperatures. The first of these was the subnitrogen meter, the true Oz concentration obviously ject’s resting oral temperature and the second was varied. If, therefore, the measured value in a given the estimated pulmonary capillary temperature, experiment fell below 0.9872, the measured value derived according to Bradley et al. (1976). The was used in eqn. (2) instead of 0.9972. This happened temperature correction affects Pa,oz, Pa,coz,PA,o~ in only four of the seventy-two O2-breathingperiods (through Pa,coz) and eva/Qt (through Cc’,02 and in twenty-four subjects. In one subject, measured Ca,oz). values Fr,oz lay between 0.9211and0.9285, with FI,N~ around 0.07. These values were presumably due to gross contamination of the oxygen supply and the Results O2-breathingdata for this subject were rejected. Venous admixture as a fraction of cardiac output Reproducibility of measurements (ova/ot) was derived via the shunt equation (eqn. 3). PA,o~ -Pa,oz. Paired t-tests for rest and the lesser
correction materially alters estimates of dead-space volume ( VD), especially during exercise.
Qva/Qt = (Cc’,oz - Ca,oz)/(Cc’,oz- CV,oZ) (3) In this, end-pulmonary-capillary Oz content (Cc‘,oz) and arterial Oz content (Ca,oz) were calculated from P A , o ~and Pa,oz respectively and from the reference temperature, arterial Pcoz, pH and haemoglobin concentration, by the computer subroutine of Kelman (1966). Mixed-venous Oz content (CV,oz) was calculated by assuming a Ca,02 - CV,oz difference of 50 ml/l at rest; in exercise, this difference was calculated from eqn. (4). Ca,oz - CV,oz = 201.4 VOz/(1003
+ Voz) (4)
exercise showed no systematic change from one member of a duplicate to the next, except for exercise with the subject breathing 02,where the first measurement exceeded the second by an average of 2.24 kPa (2P i0.05). The SD values of the differences between duplicates, regardless of sign, were: rest, air, 0.61; rest, O t , 4.14; exercise, air, 0.43; exercise, Oz, 2.44 kPa. Qva/Qt. Again, the first measurement of a duplicate during the lesser exercise, breathing 0 2 , was greater than the second by an average of 0 5 % (2P < 0.05). Otherwise no systematic change was
SD
Group C (n = 8) Mean
2P
SD
2P Group B (n = 7) Mean
SD
Oz breathing Group A (n = 8) Mean
SD
2P Group C (n = 8) Mean
SD
2P Group B (n = 8) Mean
SD
Air breathing Group A (n = 8) Mean
7253 3946
> 0.05 6639 3960
2640 4213 > 0.05
3293 4160
1613 513
2640 2720 > 0.99
2173 541
245 41.4
3-22 1.69
2.95 1.69
>0*05
1.17 1-89
1-47 1.87 >0.05
1.18 1.21 >0.98
3.32 1.25
1.49 1.21 >0.98
1.22
4.05
3.38 1.89 >040
827 707 < 0.05
2.22 2.03 >0.20
1.37 0.18 1-04 1-24 40.025 0,99
0.10
0.44 >0-10
1.07 0.59
>0.90 1.54 061
0.99 0.68
0.45 0 1 0
1.08
1.04 1-09 >0.95
1.59
0.33
0.91
1265 153
1470 155
Gas exchange during exercise in healthy people II. Venous admixture
E. A. HARRIS, EVE R. SEELYE
AND
R. M. L. WHITLOCK
CIinical Physiology Department, Green Lane Hospital, Auckland, New Zealand
(Receiued 14 July 1975)
Key words: alveolar and airway closure, exercise, venous shunt.
SummarY 1. Venous admixturelcardiac output ratio (Ova/
e t ) has been measured in twenty-four healthy volunteer subjects of both sexes aged 20-71 years, at rest and during the steady state of treadmill exercise at two rates of work, and breathing air and breathing oxygen. 2. With oxygen breathing, Ovalet was considerably less during exercise than during the time subjects were taking either normal or deep breaths of oxygen at rest, and did not significantlyincreasewith the intensity of exercise. It is postulated that the increase in ventilation during exercise opens most or all of those alveoli which, during oxygen breathing at rest, close because of critically low ventilation/ perfusion (V/Q>ratios. 3. With air breathing, Ovalet fell from rest to exercise (especially in older subjects), presumably due to improved ventilation of alveoli at the lung bases. With an increase in work rate e v a / e t increased in all age groups. This increase was not due to increase in the shunt fraction (e,/et), nor to limitation of diffusing capacity; it arose from an increase in V/Q variance. 4. Equations have been derived for the prediction of normal e v a / e t during exercise, with or without correction for the effects of increasing pulmonary capillary temperature. These effects do not materially influence the accuracy of prediction, but may be relevant to some of the interpretations. In particular, they provide a further indication that es/(& probably cannot be measured by breathing oxygen at rest, even in deep breathing. Correspondence: Dr E. A. Harris, Clinical Physiology Department, Green Lane Hospital, Auckland, New Zealand.
335
Introduction
The effects of different alveolar oxygen tensions (PA,o~)on alveolar-to-arterial oxygen-tension gradient (PA,O~ -Pa,o,) and venous admixturelcardiac output ratio (eva/et) were studied in forty-eight healthy men and women, ages 20-74 years, by Harris, Kenyon, Nisbet, Seelye & Whitlock (1974). These data provided prediction standards for normal Ova/ e t . The reduction in e v a / e t when deep, as contrasted with ordinary, breaths of oxygen were taken led to speculation as to whether ‘deep-breathreversible’ shunt might make a significant contribution to venous admixture when air was breathed, diminishing the importance of pulmonary ventilationlperfusion (310)variance. Subsequent papers by Wagner, Laravuso, Uhl & West (1974) and by Dantzker, Wagner & West (1975) point to a different interpretation, based on the selective instability of lung units with low V / eratios during oxygen breathing. This paper presents the results of studies in twentyfour healthy subjects at rest and during exercise. The objects were (1) to add to available information about the normal range of venous admixture during exercise, (2) to interpret the data in the light of the work of Wagner et al. (1974) and Dantzker et al. (1975) and (3) to assess the effect on h a l e t of correcting blood-gas tensions to pulmonary capillary temperature; in the preceding paper Bradley, Harris, Seelye & Whitlock (1976) have shown that such
336
E. A . Harris, Eve R. Seelye and R. M. L. Whirlock
where Voz was the measured Oz uptake (ml/min) during the particular exercise breathing air. Eqn. (4) was calculated from the pooled data of Epstein, Beiser, Stampfer, Robinson & Braunwald (1 967), Hermansen, Ekblom & Saltin (1970) and Levy, Methods Tabakin & Hanson (1961), who measured cardiac Subjects, procedure and laboratory methods output at various rates of work in the upright position, in healthy subjects. We were unable to find These, including details of the subject groups A, B sufficiently detailed information to warrant making and C, have been described in the preceding paper a distinction according to age. (Bradley et al., 1976). Error in the assumption of arteriovenous Oz difference affects the calculated ovalot less during exercise than at rest. For example, an error of 10 Calculations ml/l would have caused an error (in the opposite For a subject breathing air, alveolar Poz (PA,oz) sense) in ova/@ of 0.3, 0.8 and 1.0% in groups A, was calculated from the alveolar gas equation (1). B and C respectively at rest. During exercise, however, the error would have been only about 0.2% in P A , o ~= P,,oz -Pa,coz[Fr,oz +(1 -Fr,oz)/R1 (1) all age groups. Moreover, the interpretations in the where R is the exchange ratio calculated from expireddiscussion are based on mean values from groups of was calculated gas analysis. With Oz breathing, PA,o~ eight subjects, and the above errors would correspond as shown in eqn. (2). to an individual error of 28.3 ml/l (10 x J8)in arteriovenous difference. It is unlikely that the assumptions PA,o~ = 0.9972 (PB- 6.27) -Pa,coz (2) erred by more than this, and at rest especially the During the course of the experiments the mean FOZ error was almost certainly less. of the oxygen supply was found to be 0.9972, SD Two sets of values of P ~ , o ~ - P a , and o ~ ovalet 0.0050. Some of the variation was due to error of were calculated in each case,according to different measurement but sometimes, as confirmed by the reference temperatures. The first of these was the subnitrogen meter, the true Oz concentration obviously ject’s resting oral temperature and the second was varied. If, therefore, the measured value in a given the estimated pulmonary capillary temperature, experiment fell below 0.9872, the measured value derived according to Bradley et al. (1976). The was used in eqn. (2) instead of 0.9972. This happened temperature correction affects Pa,oz, Pa,coz,PA,o~ in only four of the seventy-two O2-breathingperiods (through Pa,coz) and eva/Qt (through Cc’,02 and in twenty-four subjects. In one subject, measured Ca,oz). values Fr,oz lay between 0.9211and0.9285, with FI,N~ around 0.07. These values were presumably due to gross contamination of the oxygen supply and the Results O2-breathingdata for this subject were rejected. Venous admixture as a fraction of cardiac output Reproducibility of measurements (ova/ot) was derived via the shunt equation (eqn. 3). PA,o~ -Pa,oz. Paired t-tests for rest and the lesser
correction materially alters estimates of dead-space volume ( VD), especially during exercise.
Qva/Qt = (Cc’,oz - Ca,oz)/(Cc’,oz- CV,oZ) (3) In this, end-pulmonary-capillary Oz content (Cc‘,oz) and arterial Oz content (Ca,oz) were calculated from P A , o ~and Pa,oz respectively and from the reference temperature, arterial Pcoz, pH and haemoglobin concentration, by the computer subroutine of Kelman (1966). Mixed-venous Oz content (CV,oz) was calculated by assuming a Ca,02 - CV,oz difference of 50 ml/l at rest; in exercise, this difference was calculated from eqn. (4). Ca,oz - CV,oz = 201.4 VOz/(1003
+ Voz) (4)
exercise showed no systematic change from one member of a duplicate to the next, except for exercise with the subject breathing 02,where the first measurement exceeded the second by an average of 2.24 kPa (2P i0.05). The SD values of the differences between duplicates, regardless of sign, were: rest, air, 0.61; rest, O t , 4.14; exercise, air, 0.43; exercise, Oz, 2.44 kPa. Qva/Qt. Again, the first measurement of a duplicate during the lesser exercise, breathing 0 2 , was greater than the second by an average of 0 5 % (2P < 0.05). Otherwise no systematic change was
SD
Group C (n = 8) Mean
2P
SD
2P Group B (n = 7) Mean
SD
Oz breathing Group A (n = 8) Mean
SD
2P Group C (n = 8) Mean
SD
2P Group B (n = 8) Mean
SD
Air breathing Group A (n = 8) Mean
7253 3946
> 0.05 6639 3960
2640 4213 > 0.05
3293 4160
1613 513
2640 2720 > 0.99
2173 541
245 41.4
3-22 1.69
2.95 1.69
>0*05
1.17 1-89
1-47 1.87 >0.05
1.18 1.21 >0.98
3.32 1.25
1.49 1.21 >0.98
1.22
4.05
3.38 1.89 >040
827 707 < 0.05
2.22 2.03 >0.20
1.37 0.18 1-04 1-24 40.025 0,99
0.10
0.44 >0-10
1.07 0.59
>0.90 1.54 061
0.99 0.68
0.45 0 1 0
1.08
1.04 1-09 >0.95
1.59
0.33
0.91
1265 153
1470 155
