MAXIMUM CARDIAC OUTPUT RELATED TO SEX AND AGE. Miharu MIYAMURA and Yoshiyuki HONDA

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1 Jap. J. Physiol., 23, , 1973 MAXIMUM CARDIAC OUTPUT RELATED TO SEX AND AGE Miharu MIYAMURA and Yoshiyuki HONDA Department of Physiology, School of Medicine, Kanazawa University, Kanazawa, Japan Summary Maximum cardiac output (Qmax) was determined for 233 males (aged 9 through 53 years) and 102 females (aged 9 through 20 years) by the carbon dioxide rebreathing technique during bicycle exercise. Maximum cardiac output of the males progressively increased from 12.5 to 22.0 liter/min until age 17 through 18 years and was maintained at this level until age 24 years. From age 25 years a decrease in Qmax to 16.7 liter/min by age 53 years was observed. Qmax of the females increased from a level of 10.5 liter/min at age 9 years to a Qmaximum of 15.5 liter/min at age 18 years, maintaining this level through age 20 years. Male Qmax for comparable ages above 18 years was 30 % higher than female Qmax. Using the average Qmax value of males of years as an optimum value, the decrement in Qmax with each year was approximately 0.9 %. The aerobic work capacity (maximum oxygen intake; 102.a.) of humans is known to decrease with increasing years from an optimum age (ROBINSON, 1939; ASTRAND, 1960; IKAI et al., 1970). Oxygen intake is strongly related to cardiac output and one of the limitations in oxygen intake must be in the circulatory ability to deliver oxygen to the working muscles. Unfortunately, data regarding the determination of cardiac output at VO2max have previously been reported for only a limited number of subjects representative of a narrow range in ages. Furthermore, data regarding the Qmax of females are limited. Therefore, this study was designed to systematically investigate the effect of increasing age, from 9 through 53 years, on Qmaximum cardiac output for males, and from 9 through 20 years for females. It was anticipated that such a study would define the role played by the cardiac output in the age-related decrease in maximum aerobic capacity and add to knowledge of the progressive increase in aerobic capacity of males and females during the developmental process of puberty. Received for publication September 3,

2 646 M. MIYAMURA and Y. HONDA METHODS The subjects studied were normal healthy males (n=233) and females (n= 102) ranging in age from 9 through 53 years for males and from 9 through 20 years for females. Their anthropometric data are shown in Table 1. Exercise was carried out using an incremental loading technique in a bicycle ergometer (Monark, Sweden), and the pedaling rate was kept constant at 60 rpm and timed with a metronome. All subjects were made to perform a preliminary test on the ergometer to accustom themselves to the procedure as well as to determine the work load for exhaustion within the proper work period. For this purpose, the preliminary test beginning with the properly assumed work load was performed until the near maximal load for exhaustion. Based on this preliminary test, the initial work load for each individual was chosen so that the subject could work 4-8 min before exhaustion. After 2 min pedaling with constant load ( kg-m/min), the work intensity was increased by 180 kg-m/min once every minute up to exhaustion. In some subjects, who appeared to have nearly reached exhaustion until the 3rd minute of work, the work load was kept constant until exhaustion. Maximum oxygen intake and carbon dioxide output were determined by the Douglas bag technique: Expired gas was collected in the bag every minute until exhaustion. The diameter of the connecting tube was 33 mm. To collect expired gas from children, we used a modified respiratory face mask, which was adjusted to the small size of the subjects. The inner diameter (28 mm) was also a little smaller than the respiratory valve used for adults. The volume of collected gas was measured by a dry or wet gasometer, and gas analysis was performed with the Scholander micro-gas analyzer. Cardiac output was determined by the CO2 rebreathing technique (JERNERUS et al., 1963): The partial pressure of CO2 in the artery (PaCO2)was estimated from the mean of two partial pressures of CO2 in the alveolar (PACO2) values measured with an Infrared CO2 analyzer (Beckman, LB-1) at the point of maximal expiration. The partial pressure of CO2 in the mixed venous blood (PvCO2)was estimated by rebreathing a CO2 in O2 gas mixture, a method which was devised by KLAUSEN (1965). The measurements of PACO2 and CO2 rebreathing were completed within 15 sec after exhaustion. From the Pa", and PVCO2 thus obtained the values of the content of CO2 in the arterial blood (CaCO2) and in the mixed venous blood (CVCO2) were read on a standard CO2 dissociation curve. Heart rate was calculated from the cardiometer recording measured for 15 sec immediately after exhaustion. RESULTS Table 1 summarizes average values and standard deviations for body height,

3 MAXIMUM CARDIAC OUTPUT 647

4 648 M. MIYAMURA and Y. HONDA body weight, maximum cardiac output (Qmax), maximum cardiac output per kilogram of body weight (Qmax/W), maximum heart rate (HRmax), stroke volume (SV), arterior-venous oxygen difference ((a-v)o2d), maximum oxygen intake (VO2max), and maximum oxygen intake per kilogram of body weight (VO2max/W) obtained for the different age ranges of both male and female subjects. Individual values for maximum cardiac output, maximum cardiac output per kilogram of Fig. 1. Relationship between maximum cardiac output (Qmax) and age in the male. Fig. 2. Relationship between maximum cardiac output per kilogram of body weight (Qmax/W) and age in the male.

5 MAXIMUM CARDIAC OUTPUT 649 Fig. 3. Relationship between maximum heart rate (HRmax, upper) and stroke volume (SV, lower), and age in the male. body weight, maximum heart rate, and stroke volume in the male subjects are presented in Figs. 1 through 3. There was a considerable variation in all measured variables among the subjects of the same age as shown in these figures. This tendency was also seen in females. In the female subjects, maximum cardiac output, maximum cardiac output per kilogram of body weight, stroke volume, and maximum oxygen intake were generally lower than in the male, though no apparent difference was seen in the maximum heart rate between the sexes. The average maximum cardiac output increased with advancing age until ado-

6 650 M. MIYAMURA and Y. HONDA lescence in both sexes. In the male, maximum cardiac output progressively increased until years (22.0 liter/min), then was maintained at a plateau level until years and from years decreased successively with increasing age. It was 16.9 liter/min at years old. On the other hand, in the female, it increased until years (15.0 liter/min), then remained unchanged until maturity. When maximum cardiac output was compared between the male and female subjects, the value of the former in adult age is higher by approximately 30% than that of the latter, while maximum cardiac output of the age range is nearly the same in both sex groups. Average maximum cardiac output per kilogram of body weight decreased gradually with advancing age in both male and female subjects. That is, it decreased from 416 ml/kg min of 9-10 years to 279 ml/kg min of years in the male, and from 339 ml/kg min of 9-10 years to 308 ml/kg min of years, in the female. The difference between the sexes was about 15% lower in the female adult. The average maximum heart rate gradually decreased with advancing age in the male subjects. The average stroke volume showed a tendency similar to those of both maximum cardiac output and maximum oxygen intake in both sex groups. It increased from 66 ml at 9-10 years to 120 ml at years, then decreased with advancing age in the males. In the case of females, average storoke volume increased remarkably from 57 ml at 9-10 years to 79 ml at years, and was maintained at approximately the same level until maturity. Table 2 summarizes statistical data of the relationship between body weight, body height, maximum cardiac output, and maximum oxygen intake. As seen from this table, close correlations were found between cardiac output and other variables, and the values of the correlation coefficients were seen to be significant at the P<0.001 level. DISCUSSION The adaptive capacity of the cardio-respiratory function for maximal and submaximal exercise seems to be different at different ages. Several investigations have independently been carried out to observe the exercise response in children (SHEPHARD et al., 1969; ANDERSON and GODFREY, 1971; BAR-OR et al., 1971), in young people (HANSON and TABAKIN, 1965; STENBERG et al., 1966; DOUGLAS and BECKLAKE, 1968; EKBLOM et al., 1968; HERMANSEN, 1970; FAULKNER et al., 1971; DIXON and FAULKNER, 1971), and in older subjects (HARTLEY et al., 1969). However, comparative studies of the maximum cardiac output in broad age groups are rare. BECKLAKE et al. (1965) reported data on cardiac output during submaximal exercise in a broad range of ages, and HANSON et al. (1968) and JULIUS et al. (1967) studied maximum cardiac output between the ages of 20 to 60. In the previous reports by IKAI and MIYAMURA (1970), maximum

7 MAXIMUM CARDIAC OUTPUT 651 Table 2. Relationship between body weight(w), body hight(h), maximum cardiac output(qmax) and maximum oxygen intake(vo2max) each other. M1, Male subjects under 20 years; M2, subjects older than 20 years; F, female subjects. cardiac output related to sex and age was measured in either maximal treadmill or bicycle ergometer exercises. However, we found recently that cardiac output during maximal treadmill exercise was higher than during maximal bicycle exercise, and this difference was statistically significant(miyamura and HONDA, 1972). Therefore, in the present study the maximum cardiac output was measured only in bicycle exercise. In examining the 233 males and 102 females reported here, we noticed the change in maximum cardiac output with advancing age. However, as to whether or not we could measure the real maximum cardiac output in this experiment, two problems should be considered: One is the methodological problem, and the other is the definition of "maximum cardiac output." We measured cardiac output by the CO2 rebreathing technique. However, the reliability of this method which was developed only recently may be questioned by some. It is well known that the most reliable methods for measuring cardiac output are the direct Fick or the indicator dilution methods. If, however, these methods are attempted during strenous exercise, their use is restricted to a limited type of exercise. As described by BAR-OR et al.(1971), the CO, rebreathing technique is a bloodless method, requires neither much cooperative effort of the subject nor close medical

8 652 M. MIYAMURA and Y. HONDA supervision, and can be performed in field work. MAGEL and ANDERSEN(1968) also showed the advantages of the CO2 method-it is easily applicable and can be repeated during exercise without blood sampling. SATOH et al.(1968) found a high correlation between the results by the CO2 rebreathing method and by the direct Fick method, the correlation coefficient being 0.908, P<0.01 in resting normal subjects. Furthermore, FERGUSON et al.(1968) found good correlation (r=0.86) and no significant difference between cardiac outputs obtained by the CO2 method and dye-dilution methods conducted during heavy exercise. In respect to the difinition of "maximum cardiac output," it may be questioned whether the cardiac output measured by the method of this study revealed the real "maximum cardiac output." According to ASTRAND et al.(1964), HOLM- GREN(1967), and DOUGLAS and BECKLAKE(1968), the cardiac output measured at the time of the maximum oxygen intake seems to deal as the maximum cardiac output. The VO2max is usually obtained during the exercise when the subjects become exhausted. The value of cardiac output, thus obtained in the present study, is considered to be the "maximum cardiac output." The above authors also determined the maximum cardiac output in a similar way. Furthermore, according to the experiment of OUELLET et al.(1969), cardiac output and oxygen intake increased linearly with the severity of work, and reached a plateau at nearly the same level of work load. Therefore, our subjects, who became exhausted during 4-8 min maximal work and should have reached maximum oxygen intake, were assumed to reveal maximum cardiac output in this experiment. Table 3 presents the mean and standard deviation(sd) of cardiac output and other physiological parameters in normal subjects of around 20 years old during maximal exercise ; these are data hitherto reported by many investigators. As has been emphasized before, there are differences in physiological responses to stress depending upon the type of ergometry employed. It should also be noted that maximum cardiac output was determined by the maximal bicycle exercise in the present study, and such maximum cardiac output may have lower values than those determined during maximal treadmill exercise. However, when compared with the data in Table 3, the present results are approximately the same or slightly lower. Our results might be due partly to the fact that almost all of our subjects were participating until adolescence in extracurricular physical activities. However, maximum cardiac output per kilogram of body weight is a little higher than reported by others. This discrepancy seems to be due partly to the.difference in body weight-our subjects were less heavy than those in other investigationsbecause there is a close correlation between maximum cardiac output and body weight, as can be seen in Table 2. The data on arterio-venous oxygen content difference((a-v)o2d) are lower than those of ERIKSSON et al.(1971) and HARTLEY et al.(1969). Two reasons can be considered: The first is the method of work loading. FAULKNER et al. (1971) and we(1972) found higher(a-v)o2d during maximal treadmill exercise

9 MAXIMUM CARDIAC OUTPUT 653

10 654 M. MIYAMURA and Y. HONDA than cycling, and this difference was statistically significant. Therefore, the (a- v)o2d in the present bicycle experiment would be lower than that in the treadmill exercise. The second reason is related to the CO, dissociation curve. As is well known, hemoglobin concentration increases with excercise, and the slope of the CO2 dissociation curve will be steeper during exercise. When taking account of the data on the Pco2 Cco2 relationship at different Hb concentrations reported by MCHARDY (1967), (V-a )CO2D should have increased by several percent in our exercise experiment. If this is the case, cardiac output will be several percent lower than reported in our data. However, measurement of cardiac output during maximal exercise by the CO2 technique conducted by so far previous investigators has been carried out with (v-a)co2d read on the standard CO2 dissociation curve. Furthermore, FERGUSON et al. (1968), as mentioned above, found good correlation and no significant difference between cardiac output obtained by the CO2 method based on the standard CO2 dissociation curve and the dye-dilution method conducted during heavy exercise. The low (a-v )O2D of children and females are unexplainable, but it may perhaps be due to the technique in work loading. We used a bicycle ergometer with incremental loading for all subjects. The work load was increased by 180 kg-m/min in every minute after 2 min pedaling with constant load ( kg-m/min). This magnitude of increment in work load seemed sometimes to be too great for these children and females. Therefore, they might not have accomplished their full physical activity before exhaustion because they failed to follow the pedaling rate within the rather short period after the step increase of the work load. Maximum cardiac output in the male is approximately 30% higher than in the female. This difference appeared to be almost the same magnitude as that reported by ASTRAND et al. (1964). This difference may be due not only to the differences in body weight, total blood volume, and heart volume, but also to the superior cardiac output function in the male. As shown in Figs. 1 through 3, there is a considerable variation in all variables among subjects of the same age. It appears that the relative contributions of stroke volume and heart rate to the increased cardiac output during exercise can vary considerably from subject to subject. Average maximum cardiac output increased with age until adolescence in both male and female subjects. In the males over the age of 25 years, it successively decreased with age. BRANDFON- BRENER et al. (1955) have reported that cardiac output in resting and recumbent states declined at the rate of approximately 1% per year and that during exercise cardiac output gradually decreased with age for any given work load. As shown in Table 1, when maximum cardiac output at years is taken as 100%, that at years is calculated to be 75%. Therefore, the rate of decrement is maximum cardiac output with age is approximately 0.9% per year. Thus, about the same rate of decrement in both resting cardiac output and exercise maximum

11 MAXIMUM CARDIAC OUTPUT 655 cardiac output was observed. PROFANT et al. (1972) reported 0.8% decrement in VO2max per year of age. This figure agrees well with our Qmax mentioned above. As can be seen from Table 1, the decreased maximum cardiac output in the older subjects is due to the decrease in both maximum heart rate and stroke volume. The physiological factors underlying this progressive decrease of maximum heart rate with age are not fully understood. It has been mentioned that the maximum heart rate in children was relatively lower than expected, and this could have been due to too fast an increment of work load for children in the present experiment. This means that higher maximum heart rate might have been obtained if a different loading method, such as the treadmill or ground running was instituted. Similarly, what finally limits maximum stroke volume during maximal exercise in the old subjects could have been ascribed to the combined effect of diminished total blood volume, elevated peripheral vascular resistance, and hypokinesis of cardiac contractility. The authors are greatly indebted to Dr. P. B. Raven and Dr. S. Taguchi for their invaluable discussion and criticisms. REFERENCES ANDERSON, S. D. and GODFREY, S. (1971) Cardio-respiratory response to treadmill exercise in normal children. Clin. Sci., 40: ASTRAND, I. (1960) Aerobic work capacity in emn and women with special reference to age. Acta Physiol. Scand., 49: Suppl. 169; ASTRAND, P. O., CUDDY, T. E., SALTIN, B., and STENBERG, J. (1964) Cardiac output during submaximal and maximal work. J. Appl. Physiol., 19: BAR-OR, O., SHEPHARD, R. J., and ALLEN, C. L. (1971) Cardiac output of 10- to 13-year-old boys and girls during submaximal exercise. J. Appl. Physiol., 30: BECKLAKE, M. R., FRANK, H., DAGENAIS, G. R., OSTIGUY, G. L., and GUZMAN, C. A. (1965) Influence of age and sex on exercise cardiac output. J. Appl. Physiol., 20: BRANDFONBRENER, M., LANDOWNE, M., and SHOCK, N. W. (1955) Changes in cardiac output with age. Circulation, 12: DIXON, R. W. and FAULKNER, J. A. (1971) Cardiac outputs during maximum effort running and swimming. J. Appl. Physiol., 30: DOUGLAS, F. G. V. and BECKLAKE, M. R. (1968) Effect of seasonal training on maximal cardiac output. J. Appl. Physiol., 25: EKBLOM, B., ASTRAND, P. O., SALTIN, B., STENBERG, J., and WALLSTROM, B. (1968) Effect of training on circulatory response to exercise. J. Appl. Physiol., 24: ERIKSSON, B. O., GRIMBY, G., and SALTIN, B. (1971) Cardiac output and arterial blood gases during exercise in pubertal boys. J. Appl. Physiol., 31: FAULKNER, J. A., ROBERT, D. E., ELK, R. L., and CONWAY, J. (1971) Cardiovascular responses to submaximum and maximum effort cycling and running. J. Appl. Physiol., 30: FERGUSON, R. J., FAULKNER, J. A., JULIUS, S., and CONWAY, J. (1968) Comparison of cardiac output determined by CO2 rebreathing and dye-dilution methods. J. Appl. Physiol., 25: HANSON, J. S. and TABAKIN, B. S. (1965) Comparison of the circulatory response to upright

12 656 M. MIYAMURA and Y. HONDA exercise in 25 normal men and 9 distance runners. Brit. Heart J., 27: HANSON, J. S., TABAKIN, B. S., and LEVY, A. M. (1968) Comparative exercise-cardiorespiratory performance of normal men in the third, fourth, and fifth decades of life. Circulation, 37: HARTLEY, L. H., GRIMBY, G., KILBOM, A., NILSSON, N. J., ASTRAND, I., BJURE, J., EKBLOM, B., and SALTIN, B. (1969) Physiological training in sedantary middle-aged and older men. Scand. J. Clin. Lab. Invest., 24: HERMANSEN, L., EKBLOM, B., and SALTIN, B. (1970) Cardiac output submaximal and maximal treadmill and bicycle exercise. J. Appl. Physiol., 29: HOLMGREN, A. (1967) Cardiorespiratory determinants of cardiovascular fitness. Canad. Med. Ass. J., 96: IKAI, M. and MIYAMURA, M. (1970) Maximum cardiac output in ordinary Japanese related to sex and age. Res. J. Phys. Educ., 14: (in Japanese). IKAI, M., SHINDO, M., and MIYAMURA, M. (1970) Aerobic work capacity of Japanese people. Res. J. Phys. Educ., 14: JERNERUS, R., LUNDIN, C., and THOMSON, D. (1963) Cardiac output healthy subjects determined with a CO2 rebreathing method. Acta Physiol. Scand., 59: Juuus, S., AMERY, A., WHITLOCK, L. S., and CONWAY, J. (1967) Influence of age on the hemodynamic response to exercise. Circulation, 36: KLAUSEN, K. (1965) Comparison of CO2 rebreathing and acethylene methods for cardiac output. J. Appl. Physiol., 20: MAGEL, J. R. and ANDERSEN, K. L. (1968) Cardiac output in muscular exercise measured by the CO2 rebreathing procedure. In Ergometry in Cardiology, ed. by DENOLIN, H. et al. Symposium organized by European Soc. Cardiol., Mannheim, Boehinger, pp MCHARDY, G. J. R. and GODFREY, S. (1967) The relationship between the difference in pressure and content of carbon dioxide in arterial and venous blood. Clin. Sci., 32: MIYAMURA, M. and HONDA, Y. (1972) Oxygen intake and cardiac output during maximal treadmill and bicycle exercise. J. Appl. Physiol., 32: OUELLET, Y., POH, S. C., and BECKLAKE, M. R. (1969) Circulatory factors limiting maximal aerobic exercise capacity. J. Appl. Physiol., 27: PROFANT, G. R., EARLY, R. G., NILSON, K. L., KUSUMI, F., HOFER, V., and BRUCE, R. A. (1972) Responses to maximal exercise in healthy middle-aged women. J. Appl. Physiol., 33: PUGH, L. G. C. E. (1964) Cardiac output in muscular exercise at 5,800m (19,000 ft). J. Appl. Physiol., 19: ROBINSON, S. (1939) Experimental studies of physical fitness in relation to age. Arbeitsphysiologie, 10: SATOH, T., IwAmoTo, M., and OYAMA, Y. (1968) Determination of cardiac output by rebreathing method; with special reference to its reliability and merit in clinical use. Jap. Circ. J., 32: SHEPHARD, R. J., BAR-OR, A. O., DAVIES, C. T. M., DEGRE, S., HEDMAN, R., ISHII, K., KANEKO, M., LACOUR, J. R., PRAMPERO, P. E., and SELIGER, V. (1969) The capacity of Tronto schoolchildren. Canad. Med. Ass. J., 100: STENBERG, J. B., EKBLOM, B., and MESSIN, R. (1966) Hemodynamic response to work at simulated altitude, 4,000 m. J. Appl. Physiol., 21:

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