Effects of age on ventricular performance during graded supine exercise

Effects of age on ventricular performance during graded supine exercise To assess the effects of age on ventricular performance, graded supine exercise tests with equilibrium radionuclide ventricuiography were performed in six normal subjects of mean age 37 ? 4 years and in eight normal subjects with a mean age of 5g ?X 2 years. At a standard submaximal work load, older subjects had a similar heart rate (older: 126 k IO, younger: 128 * 5 bpm) and systolic blood pressure responses (older: lg8 * 24, younger: 202 ? 24 mm Hg). Cardiac output counts increased appropriately in both groups during submaximal exercise. However, when expressed as percent change from resting values, the increases in cardiac output (older: 125 ? 14, younger: 75 2 10 L/min; p < 0.05) were greater for the older subjects. The percent change in end-diastolic counts (older: 8.4 ? 5, younger: -2.8 ? 4), stroke counts (older: 26 ? 6, younger: 8.6 ? 4), and ejection fraction (older: 18 * 3, younger: 11 ? 1%) in proceeding from rest to exercise Stage Ill (600 kg-m/min) was greater for the older subjects. Age-related differences in each of these measurements were significant at p < 0.05. These findings suggest that cardiac output during exercise is maintained by an increased heart rate in younger subjects, and by a combination of increased heart rate and the Frank-Starling mechanism in older individuals. Since the heart rate and mean blood pressure response to exercise were similar in both groups, the use of the Frank-Starling mechanism during exercise in older subjects suggests that age-related differences in ventricular preload are important in modulating the performance of the aging left ventricle. (AM HEART J 111:108, lg86.)

Douglas L. Mann, M.D., Barry S. Denenberg, M.D., Arnold K. Gash, M.D., P. Todd Makler, M.D., and Alfred A. Bove, M.D., Ph.D. Philadelphia,

Pa., and Rochester,

Minn.

The impact of aging on the cardiovascular system has been the subject of considerable research since Master and Oppenheimer described the decrease in work capacity of older individuals in 1929.l While unanimity does not exist,2 the great majority of studies have indicated that aging is associated with a decline in maximal oxygen uptake and cardiac output during exercise. 3-s However, despite extensive research in this area, it is uncertain whether this decline is related to changes in ventricular “pump” function or to changes in the peripheral vasculature or skeletal muscle. The advent of radionuclide ventriculography has provided a simple noninvasive means for assessing ventricular performance in the elderly. Thus far, these noninvasive studies have examined the ventricular performance of older indiFrom the Cardiology Section, Department of Medicine, Temple Medical School; and Cardiovascular Division, Mayo Clinic. Supported by National tutes of Health, Grant Received accepted

for publication July 8, 19&35.

Heart, Lung, No. HL-28473. Jan.

and Blood

4, 198$

Reprint requests: Alfred A. Bove, M.D., Mayo Clinic, Rochester, MN 55W5.

revision Ph.D.,

Institute, received

University

National June

Cardiovascular

Insti-

10, 1985: Division,

viduals during upright exercise.zn lo The first such study, by Port et al.,l” suggested that aging is associated with a decline in the exercise ejection fraction. These authorslo concluded that aging is associated with a decline in the “contractile reserve” of the ventricle. In contrast, a recent report by Rodeheffer et al2 suggests that exercise ejection fraction remains unchanged throughout most of exercise, md that cardiac output is maintained by a combination of increased heart rate and the FrankStarling mechanism. It is of interest that Port et aLlo did not detect such an increase in end-diastolic volume in their exercising older subjects. Since ejection phase indices of ventricular performance are dependent on loading conditions,ll we considered it possible that the differences in ventricular performance observed by Port et aLlo and by Rodeheffer et al2 were the result of different loading conditions rather than differences in contractile performance. The purpose of the present study was to examine the ventricular performance of older subjects during graded supine exercise. Supine rather than erect exercise was chosen, since ventricular filling pres-

“Ohm Number

111

LV performance

1

sure in the supine position in normal individuals is thought to be above the steep portion of the ventricular function (Starling) curve.12 Thus, although there might be small differences in ventricular preload between groups at rest, these differences would be less likely to &ect ejection phase indices of ventricular performance. METHODS The patient population consisted of six normal subjects (all men) all less than or equal to 50 years old (37 & 4 years; mean ? SEM) and eight normal subjects (two women, six men) older than 50 years (59 2 2). Six of the older subjects and two of the younger subjects were referred for nonanginal chest pain; the remaining subjects were referred for evaluation of functional capacity. All patients had a normal chest x-ray examination and ECG. Moreover, there was no past medical history suggestive of organic heart disease and no evidence of valvular heart disease on physical examination. None of the patients was taking diuretics, nitrates, beta-blocking agents, calcium channel blockers, or digitalis preparations; furthermore, all noncardiovascular medications were stopped 24 hours prior to exercise testing. During exercise and the ensuing recovery period, no subject developed chest pain or shortness of breath, ST-T changes suggestive of &hernia (i.e., >l mm ST depression in any lead), radionuclide ventriculographic yall motion abnormalities, or a decline in the radionuclide ejection fraction. None of the subjects was engaged in a regular exercise program at the time of testing. All subjects were studied as part of an outpatient clinical evaluation which included referral for a radionuelide exercise test. In all cases exercise testing was performed in order to provide proper advice for levels of activity. Exercise protocol. All exercise studies were performed in the supine position on a standard bicycle ergometer. Subjects were tested to a symptom-limited maximum defined as weakness, fatigue, or leg pain. Heart rate, exercise ECG, and brachial artery cuff blood pressure were recorded at rest and at each stage of exercise. Graded multilevel exercise was performed for 3 minutes at each level, starting at workloads of 200 kg-m/min. Increments of 200 kg-m/min were added at each successive stage of exercise. Count data acquisition and hemodynamic measurements were collected at rest in the “leg up” position and during the second through third minute of each stage of exercise. Count data were acquired in this manner to allow for equilibration of heart rate. Radionuclide technique. After in vivo labeling of the patient’s red blood cells with 20 mCi of technetium-99m pertechnetate by the method of Pave1 et al.,13 equilibrium multiple gated acquisition studies were performed in the 35- to 45-degree left anterior oblique projection, with the camera angle varying from patient to patient to give the best visualization of the interventricular septum. The energy window was centered at 140 keV. The window was usually set at 20%, and was occasionally reduced to 15 y0

Table I. Heart rate younger subjects*

response

to exercise

Older E.7 stage 0

I II III Peak Ex

HR Rwn) 84 103 117 126 142

Ik * & 2 *

in older

109

and

Younger 7; ma

7 8 8 IO 9

and aging

40 56 66 71 79

Hr Rwnl 80 100 114 128 161

k k k zk ?

7; max

Pt

44 52 60 70 88

NS NS NS NS NS

4 6 5 5 8

Ex = exercise; HR = heart rate; NS = nonsignificant. *Data are mean ? SEM. tp value refers to differences in the percent maximal between groups.

heart

rate response

to avoid saturating the counting capacity of the computer system. The window setting for each patient remained the same throughout all studies. Data were acquired utilizing a low-energy, all-purpose parallel hole collimator and a General Electric scintillation camera interfaced with a commercially available computer system (Medical Data Systems-Simul, Ann Arbor, Mich.). Count data were stored on a 64 X 64 image matrix utilizing a standard commercially available computer system (MUGX). Left ventricular time-activity curves were generated for each patient with the standard computer system (MDSAZ). A semiautomatic edge detection system determined the boundaries of the left ventricle in each frame. Background subtraction was performed with an automated computer-selected region of interest adjacent to the left ventricle at end systole. Counts were thus obtained over the left ventricle for each frame. The end-diastolic frame was defined as that frame during the cardiac cycle with a maximum number of counts within the region of interest. The end-systolic frame was defined ati that frame with the minimum number of counts within the region of interest over the left ventricle. Both end-diastolic and end-systolic counts were corrected for technetium-99m isotope decay. We used the standard equation advocated by Dehmer et al.? & = R,,e - 0.693t/T%, where & is the activity at any time (t), R0 is the activity of the sample at time zero, and T’ is the half-life of the isotope (360 minutes for technetium) administered. End-diastolic and end-systolic counts were corrected with the formuCobs la: Ccor = where Ccor Cycles collected X time/frame ’ are the corrected counts and Cobs are the observed counts. This correction was performed so that count data could be compared at different heart rates during each stage of exercise. Thus a change in count data represented a change in volume rather than a change in counts, due to a changing number of cardiac cycles collected during a given exercise stage. The values for end-diastolic counts and ejection fraction were determined by two independent observers. The interobserver variability for each parameter was less than

110

Mann

et al. A-NS

stage kg-m min

I 200 3

rest 0 0

II 400 6

ill 600 9

stage kg-m min

rest 0 0

I 200 3

II 400 6

Ill 600 9

1. Heart rate and systolic blood pressure response to exercise in older (solid line) and younger (dashed line) subjects at rest (0) and with submaximal exercise (I to III). All values are expressed as the mean 5 SEM. Levels of significance for age (A) and exercise (E) effects, obtained from two-way analysis of variance, are indicated for each of the plots.

Fig.

Table

Il. Left ventricular response to exercise in older and younger patients* Exercise

stage

0

End-diastolic counts

Older Younger Older Younger Older Younger

End-systoliccounts Stroke counts Cardiac

output

counts

(X10-21

Ejection fraction (percent)

5%, and intraobserver variability

Older Younger

Older Younger

613 720 256 318 354 398 278 311 58 -55

for these parameters

was less than 3 % . Hemodynamic data. The left ventricular ejection fraction was determined by dividing the stroke counts by the end-diastolic counts. The cardiac output in counts was calcuIated by multiplying the heart rate by the number of stroke counts. We utilized count-derived changes rather than absolute ventricular volumes. This technique, validated by Sorensen et al.,14 has excellent reproducibility and correlates closely with Fick-derived cardiac output data. Moreover, count-derived changes are relatively independent of geometric assumptions about the ventricle (which might differ in older and young subjects). Percent changes in each measured variable from baseline were calculated

as;

observed counts-baseline baseline counts

counts

x100.

Statistical analysis. Statistical analysis of the hemodynamic data was performed by analysis of variance and Student’s paired t test. A two-way analysis of variance testing for both age (i.e., differences arising between the groups) and exercise effects (i.e., differences arising within

I

iz ? I!I ? 2 zk k k 2 k

65 61 24 33 45 38 36 18 2 2

659 766 260 311 400 455 398 439 60 ,5S

k * k zk zk * rk 2 2 *

II 65 86 25 34 42 59 46 43 1 3

652 716 234 288 4lS 432 468 482 63 60

rk 69 k 77 k 26 z!L 39 2 49 k 47 k .V 2 43 k 2 * 3

III 664 708 216 278 44S 438 502 552 6S 62

k 7S * 84 k 26 Y!z 41 IL 61 k 51 * 35 k 34 k 3 k 3

each group) was used. All data were expressed as mean 2 standard error of measurement. The level of significance for all studies was defined at the p < 0.05 level. RESULTS Response to exercise. The exercise data for older and younger subjects are summarized in Table I and Fig. 1. Although the symptom-limited maximal work load was significantly greater for younger subjects (1100 & 105 vs 675 & 80 kg-m/min, p < O.Ol), at peak exercise there was no significant difference between groups in systolic blood pressure (older group: 204 & 9 mm Hg, younger group: 228 & 12 mm Hg), or the heart rate response expressed as actual values (older group: 142 ? 9 bpm, younger group: 161 ? 8 bpm) or as a percent of predicted maximum heart rate (older group: 79%, younger group: 88%). In order to facilitate comparison between older and younger subjects at the same absolute and relative work loads, analysis of the data was confined to submaximal levels of work (rest through 600 kg-m/min).

Volume ill Number I

L V performance

END-DIASTDLIC CDUNTS

and aging

111

END-SYSTDLIC COUNTS A< llO5 EC ~J05

-

q q

750 Years Old G 50 km Old

A<005 Ec005

STAGE KG-M MIN

I

II

200 3

400 6

III

600 9

STROKE COUNTS

200 3

400 6

600 9

CARDIAC OUTPUT COUNTS

Fig. 2. Left ventricular size and performance during exercise in older (open bars) and younger (hatched bars) subjects. End-diastolic counts, end-systolic counts, stroke counts, and cardiac output counts are

expressed as percent change data from resting values. The levels of submaximal exercise (200 to 600 kg-m/min) are depicted along the abscissa. All data points are expressed as mean ? SEM. Levels of significance obtained from two-way analysis of variance, testing for age (A) and exercise (El effects, are indicated for each of the plots.

The actual heart rate response to submaximal exercise is displayed in Fig. 1. Although older and younger subjects both increased their heart rate response significantly, analysis of variance indicated that there was no significant difference between groups in the actual heart rate response. Furthermore, when the heart rate response was expressed as a percent of maximum heart rate (Table I), no significant difference was observed between groups. The systolic blood pressure response during exercise is summarized in Fig. 1. Analysis of variance indicated a significant exercise effect over the course of submaximal exercise, but no significant difference between groups (age effect). Mean blood pressure was also not different between the groups (restolder: 110 k 4, younger: 114 * 5 mm Hg; Stage III-older: 133 * 4, younger: 131 & 7 mm Hg).

Left ventricular size and performance. Actual count data for end diastole, end systole, stroke output, cardiac output, and ejection fraction are presented in Table II. The normalized values for these data, expressed as percent change from resting values, are displayed in Figs. 2 and 3. Statistical analysis was performed on the normalized data. At the beginning of exercise, both older and younger subjects increased their end-diastolic size; however, whereas older subjects maintained this increase in enddiastolic size throughout exercise, the younger subjects decreased their end-diastolic size with increasing levels of work (Fig. 2). An analysis of variance indicated significant changes in end-diastolic size within each group, but no significant differences in end-diastolic size between the groups. Since the statistical evaluation of age effect may have been

112

Mann

et al.

American

DISCUSSION

25

0 STAGE KG-VI MIN

January, 1966 Heart Journal

1 200 3

II

III

The major finding of this study is that older subjects utilized the Frank-Starling mechanism during supine exercise. Whereas younger subjects increased their exercise cardiac output largely through an increase in heart rate, older subjects utilized a combination of increased heart rate and stroke output to augment exercise cardiac output. Importantly, the increase in stroke output in the older subjects was mediated through an increase in end-diastolic size (Frank-Starling mechanism); however, this increase in size was not the result of a slower heart rate in the older group, as has been previously suggested.z

400 6

600 9

Invasive

EJECTION FRACTION PERCENT Fig. 3. Ejection fraction response to exercise in older (open bars) and younger (hatched bars) subjects. The

ejection fraction is expressed as a percent change from resting value. The levels of submaximal stress (200 to 600 kg-m/min) are depicted along the abscissa. Data points are expressed as the mean * SEM. Analysis of variance was significant for age (A) and exercise (E) effects. influenced by exercise-related variation in the data (introduced by the negative changes in the younger

group at stages II and III), we compared the difference in end-diastolic size at stages I to III by t test. When analyzed in this manner, the difference in end-diastolic size at stage III was significant. Endsystolic size diminished progressively in both groups during exercise (Fig. 2). Although the decrease in end-systolic volume was only slightly greater for older subjects, the differences in systolic performance were significant for both age and exercise effects. Fig. 2 also demonstrates that whereas the stroke counts of younger subjects tended to plateau

during the latter stages of work, the stroke output of older individuals increased significantly with progressive exercise. During exercise the cardiac output counts increased in both groups (Fig. 2); however, the relative increase in cardiac output was significantly greater for older individuals. To exclude the possibility that inclusion of the two older female subjects might have biased the results, the statistical analysis of end-diastolic and end-systolic counts, cardiac output counts, and ejection fraction response was repeated without the female subjects; the conclusions were the same. Ejection fraction increased significantly in both groups with exercise (Fig. 3); furthermore, the relative increase in ejection fraction was significantly greater for older subjects.

Hemodynamic

nath

profile

of exercising

studies on healthy

et al.,5 Strandel,6

older individuals.

older subjects by Gra-

and Julius

et al.8 indicate

that as oxygen uptake increased during exercise, the heart rate response was similar in older and younger individuals; however, at any given level of oxygen uptake, the cardiac output was lower in the older group. These investigators attributed this difference to smaller stroke volumes in the older group.5x6z8Yet it is unclear from their data whether the age-related decline in stroke volume stems from changes in cardiac “pump” function or peripheral circulatory changes. Proposed mechanisms for the smaller stroke volumes in the elderly include differences in preload due to decreased compliance of the ventricles,15 increased afterload due to changes in aortic impedance,‘jp l6 as well as alterations in the contractile state of the myocardium secondary to a diminished response to catecholamines.14y 17-~gIt has even been proposed by some that the age-related changes in the elderly may simply be the result of deconditioning,K XT21 although a recent study testing this hypothesis suggests that exercise training does not improve ventricular performance in the aged.zz In a survey of catheterization data,33 we noted that resting indices of left ventricular performance were not depressed in normal older individuals. Recent noninvasive studies suggest that the hemodynamic profile of exercising older individuals differs from that of younger individuals. With the use of radionuclide ventriculography, Port et al.l” detected an age-related decline in ejection fraction during upright exercise. These authors attributed this change to a reduced “contractile

elderly. More recently,

Rodeheffer

reserve” in the

et al2 reported

that the radionuclide ventriculographic ejection fraction and cardiac output are not diminished during upright exercise in older individuals. In contrast to previous invasive studies,5s c ‘9g these authors reported an age-related increase in stroke volume during exercise, which they attributed to the

Volume 111

LV performance

Number 1

use of the Frank-Starling mechanism by older subjects. Rodeheffer et al.* concluded that the use of the Frank-Starling mechanism compensated for the slower heart rate observed in their exercising older individuals. With the use of echocardiography during semi-supine exercise, Van Tosh et al.23 reported similar findings; however, these authors did not observe a significant difference in heart rate response between their older and younger subjects. The hemodynamic profile of our exercising older individuals is in overall agreement with previous invasive and noninvasive studies.zv 5s6v*ps*23 The significant increase in cardiac output (counts) detected in our older and younger subjects has been previously reported by others ;5s6s**s However, our findings suggest that the relative increase in cardiac output with exercise was greater for older individuals. Similar findings were reported by Julius et al.8 With exercise, we noted a significant (p < 0.05) increase in the exercise ejection fraction of our older subjects (Fig. 3). In this regard, our findings differ from those reported by Port et aLlo and by Rodeheffer et al.* One possible explanation for the difference in exercise performance between older and younger subjects might be that although both groups exercised at the same absolute work loads, this work load was relatively greater for the older subjects. However, the observation that the percent of maximum predicted heart rate response was similar between groups (Table I) suggests that the older and younger subjects exercised at the same absolute and relative work loads. In the present study, striking differences in the stroke count response to exercise were observed in older and younger individuals (Fig. 2). Whereas the stroke output of younger individuals tended to plateau at successive work loads, older subjects continued to increase their stroke output throughout exercise. Our findings suggest that these differences in stroke output are the result of the disparate changes in end-diastolic size between the two groups (Fig. 2). Thus our results are in overall agreement with the noninvasive studies of Rodeheffer et al.* and Van Tosh et al.,23 and the invasive study by Granath et al.,5 who observed that individuals with the greatest increases in filling pressure during exercise also had the greatest increases in cardiac output and oxygen uptake. Use of the Frank-Starling

mechanism

during

exercise.

Despite extensive studies in man, the data on left ventricular volumes and performance during exercise remain inconclusive.z4p25 Most studies indicate that the Frank-Starling mechanism is not operative in normal subjects during supine submaximal exercise.24*z6,z7In the present study, the exercise performance of our younger group was similar to that

and aging

113

reported by others;z8-30 we observed that younger subjects utilized mainly heart rate response to increase their cardiac output during submaximal exercise. However, the left ventricular performance of our older group differed. These individuals relied on a combination of increased heart rate and stroke volume to increase their cardiac output. Our data suggest that the proportionately greater increase in stroke volume counts in the older group is achieved through a small but significant increase in enddiastolic size (Fig. 2). Although our findings are in overall agreement with those of Rodeheffer et al.,* we cannot attribute the increase in end-diastolic size to differences in heart rate as they did, since the heart rate response to exercise was similar in both groups (Fig. 1). Conceivably, we might have noticed a difference in heart rate response between groups at higher work loads. However, the important observation was that a slower heart rate was not necessary for the development of the Frank-Starling effect in our older subjects. Thus, our findings are in accord with those of Van Tosh et al.23 Since there was no difference in the systolic blood pressure between older and younger subjects during exercise (Fig. 1), it is unlikely that differences in afterload alone were responsible for the increase in end-diastolic size noted in our older subjects. One possible explanation for our findings might be that there is an age-related decrease in ventricular compliance, as suggested by the experimental studies of Templeton et all5 If so, one might predict that at a given filling pressure the less compliant ventricles of older subjects would start at a lower point along the diastolic pressure-volume curve. Consequently, with increased venous return during exercise, the relative increase in end-diastolic size would be greater for the older subjects, albeit at the expense of higher filling pressures. In a survey of catheterization data,33 however, we did not observe a significant age-related increase in left ventricular end-diastolic volume or pressure in normal older individuals. An alternative explanation might be that the increase in central blood volume (i.e., heart and lungs) observed during supine exercise31* 32 is relatively greater in older individuals. Accordingly, venous return (and hence end-diastolic volume) might be expected to be relatively greater in exercising older individuals. Study design. Although there might be concern that chronic disease, and not age, produced the observed changes, none of our patients had evidence of cardiovascular disease on physical examination, resting or exercise ECG, or chest roentgenogram. In addition, we used accepted noninvasive methods similar to those used by Port et al.,*O and Rodeheffer

January,

114

Mann

et al.

et al.2 to exclude coronary heart disease: absence of exercise-induced symptoms or changes in the exercise ECG; absence of stress-induced ventriculographic wall motion abnormalities; and absence of exercise-induced abnormalities in ejection fraction. The sensitivity of these techniques for detecting coronary heart disease approaches 85 % 35-37Lastly, a recent investigation by Hakki et a13* suggests that older individuals with angiographically demonstrated coronary heart disease do not use the FrankStarling mechanism during exercise. Thus, while we cannot entirely exclude coronary artery disease in our older subjects, their hemodynamic response during exercise is neither typical nor suggestive of coronary heart disease. conchsions. The major finding of this study is that older individuals use the Frank-Starling mechanism during supine submaximal exercise. Although we have not delineated the exact mechanism(s) responsible for this increase in end-diastolic size during exercise, and data suggest that this increase in size is not the result of a slower heart rate in older subjects. While we agree with Rodeheffer et al2 that “beta-adrenergic modulation of myocardial contractility, heart rate, and vascular tone declines with age,” our data do not support their hypothesis2 that beta-adrenergic modulation “alone is sufficient to explain all of the age-related changes.” Indeed, our data, as well as those of Van Tosh et al.z3 suggest that a single mechanism is insufhcient to explain the changes in hemodynamic response in exercising older individuals. It is likely that loading conditions of the ventricle, possibly as a result of differences in venous return or perhaps ventricular compliance, are also important in modulating the ventricular performance of exercising older individuals. REFERENCES

AM, Oppenheimer ET A simple exercise tolerance 1. Master test for circulatory efficiency with standard table for normal individuals. Am J Med Sci i77:223, 1929. RJ. Gerstenblith G. Becker JC. Flea JL. Weis2, Rodeheffer feldt ML, Lakatta EG Exercise’cardiac output is-maintained with advancing age in healthy subjects: Cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 69:203, 1984. M, Landowne M, Shock NW: Changes in 3. Brandfonbrenner cardiac output with age. Circulation 12:5X, 1955. 4. Cournand A, Riley RL, Breed ES, Baldwin E, Richards DW: Measurements of cardiac output in man using the technique of catheterization of right auricle or ventricle. J Clin Invest 24:106, 1945. 5. Granath A, Jonsson B, Strandel T: Circulation in healthy old men, studied by right heart catheterization at rest and during exercise in supine and sitting position. Acta Med Stand 176:424, 1964. T: Cardiac outnut in old age. Zn Carid FT, Doll JLC, 6. Strandel Kennedy RD, editors: Cardiology in old age. New York, 1967, Plenum Press, p. 160.

American

Heart

1986 Journal

7. Lewis WH: Changes in cardiac output in adult men. Am J Physiol 121:517, 1938. 8. Julius S, Amery A, Whitlock LS, Conway J: Influence of age on the hemodynamic response to exercise. Circulation 36~222,

1967.

9. Strandel T: Circulation studies on healthy old men. Acta Med Stand (suppl) 414:1, 1964. 10. Port S, Cobb F, Coleman RE, Jones RH: Effect of age on the response of left ventricular ejection to exercise. N Engl J Med 303:

1133,

1980.

11. Peterson KL, Sklovan D, Lundbrok P, Uther JB, Ross J: Comparison of isovolumetric and ejection phase indices of myocardial performance in man. Circulation 49:1088, 1974. 12. Parker JO, Case RB: Normal ieft ventricular function. Circulation 60:4, 1979. 13. Pave1 DG, Zimmer AM, Patterson UN: In vivo labelling of red blood cells with Tc: A new approach to blood pool visualization. J Nucl Med 16:305, 1977. 14. Sorensen S. Ritchie *J. Caldwell J. HamiRon G. Kennedv ,JW Validation ‘of count-derived changes in cardiac outpui and quantitation and maximal exercise ventricular volume changes after nitroglycerin and propranolol in normal men. Circulation 61:600, 1980. 15. Templeton GH, Platt MR, Willerson .JT, Weisfeldt ML: Influence of aging on left ventricular hemodynamics and stiffness in beagles. Circ Res 44:189, 1979. 16. Gerstenblith G, Lakatta EG, Weisfeldt ML: Age change in myocardial function and exercise response. Prog Cardiovasc Dis 19:1, 1976. 17. Dehmer G,J, Lewis SE, Millis LD, Twieg D, Falkoff M, Parkey, RW, Willerson .JT: Nongeometric determination of left ventricular volumes from equilibrium blood pool scans. - Am .J Cardiol 45:233, 1980. * 18. Yin FC, Spurgeon HA, Greene HL, Lakatta EG, Weisfeldt ML: Age-associated decrease in heart rate response to isoproterenol in dogs. Mech Ageing Dev l&17, 1979. 19. Gerstenblith G, Spurgeon HA, Froelich JJP, Weisfeldt ML, Lakatta EG: Diminished ionotropic responsiveness to ouabain in aged rat myocardium. Circ Res 44:517, 1979. 20. Asmussen E. Mathiasen P: Some nhvsiological functions in physical education students reinvestcgated-after twenty-five years. J Am Geriatr Sot 30:379, 1972. 21. Kanstrup IL, Ekbom B: Influence of age and physical activity on central hemodynamics and lung function in active adults. J Appl Physiol 4&:709, 1978. 22. Schocken DD. Blumenthal JA. Port S. Hindle P, Coleman RE: Physical conditioning and’ left ventricular performance in the elderly. Am J Cardiol 52:359, 1983. 23. Van Tosh A, Lakatta EG, Fleg JL, Weiss J, Kallman C, Weisfeldt ML, Gerstenblith G: Ventricular dimension changes during submaximal exercise. Effect of aging in normal man (abstr). Circulation 63(suppl 111):129, 1980. 24. Vatner S, Pagani M: Cardiovascular adjustments to exercise: Hemodynamics and mechanisms. Prog Cardiovasc Dis 19:91, 1976. 25. Poliner L, Dehmer G, Lewis S, Parkey R, Blomqvist G, Willerson J: Left ventricular performance in normal subjects: A comparison of the response to exercise in the upright and supine position. Circulation 62:528, 1980. 26, Braunwald E, Goldblatt D, Harrison D, Mason D Studies on cardiac dimensions in intact, unanesthetized man. III. Effects of muscular exercise. Circ Res 13:460, 1963. 27. Braunwald E, Sonnenblick E, Ross J, Glick G, Epstein S: An analysis of the cardiac response to exercise. Circ Res 20 and 21 (suppl 1):44, 1967. 28. Rushmer R: Constancy of stroke volume in ventricular responses to exertion. Am J Physiol 196:745, 1959. 29. Chanman C, Fisher J, Snroule B: Behavior of stroke volume at rest and .during exercise in human beings. J Clin Invest 39:549, 1960. 30. Wang Y, Marshall R, Shepard J: The effect of changes in

Volume II 1 Number

31. 32. 33. 34.

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posture and of graded exercise on stroke volume in man. J Clin Invest 39:1051, 1960. Braunwald E, Kelley El? The effect of exercise on central blood volume in man. J Clin Invest 39:413, 1960. Mitchell JH, Sproule BJ, Chapman CB: Factors influencing respiration during heavy exercise. J Clin Invest 37:1693, 1958. Bodurian E, Santamore WP, Bove AA: Effect of coronary artery disease on the aging hearti Observations from cardiac catheterization, J Gerontol 39:170, 1984. Hakki A-H, DePace NL, Iskandrian AS: Effect of age on left ventricular function during exercise in patients with coronary artery disease. ,J Am Co11 Cardiol 2:645, 1983.

35. Borer J, Kent K, Bacharach S, et ab Sensitivity, specificity and predictive accuracy of radionuclide tine angiography during exercise in patients with coronary artery disease. Circulation 6&572, 1979. 36. Verani MS, Del Ventura L, Meiler RR: Radionuclide ventriculograms during dynamic and isometric exercise in coronary artery disease; comparison with exercise thallium-201 scintigrams. Clin Res 27:211, 1979. 37. Kirshenbaum H, Okada R, Kushner FG: The relation of global left ventricular function with exercise to thallium-201 exercise scintigrams. Clin Res 27:180, 1979,

Left ventricular structure and function in normotensive adolescents with a genetic predisposition to hypertension It has been SUQQeSbd that the heart plays an active role in the pathogenesis of arterial hypertension. If this is true, there must be early cardiac involvement in young normotensive subjects who develop hypertension later in life and differences in cardiac morphology or function may exist between young normotensive subjects with different risks of developing hypertension. M-mode echocardiography was performed in 51 normotensive male adolescents with at least one hypertensive parent (SHT). These subjects were compared with 55 normotensive sons of normotensive parents (SNT) and with 25 adolescents with borderline hypertension (BH). Control groups were matched for sex and age. The following morphologic parameters were significantly greater in the SHT group than in the SNT group: interventricular septum (0.54 ? 0.08 vs 0.49 ? 0.09 cm/m’; p < 0.01) and posterior wall (0.54 & 0.11 vs 0.50 ? 0.08 cm/mz; p < 0.05) thickness, left ventricular mass (125.0 + 29.1 vs 109.2 ? 25.4 gm/mz; p < 0.005), and cross-sectional area (g.Q * 1.8 vs 8-g * 1.6 cmz/m2; p < 0.005). No significant differences between SHT and BH subjects were observed. Excursion of left ventricular posterior wall was significantly higher in the BH group. No differences were observed between SHT and SNT subjects. These data show that the same kinds of changes in cardiac morphology are present in normotensive subjects with a family history of hypertension and in subjects with borderline hypertension, suggesting that cardiac involvement may precede elevation of blood pressure. (AM HEART J 111:115, 1986.)

Maria Radice, M.D., Claudio Alli, M.D., Faust0 Avanzini, M.D., Marco Di Tullio, M.D., Giancarlo Mariotti, M.D., Emanuela Taioli, M.D., Alessandro Zussino, M.D., and Giuseppe Folli, M.D., Milano,

Italy

The hemodynamic changes which lead to the development of arterial hypertension are not yet known. It has been suggested that the heart plays an active From

the Clinica

Received accepted Reprint Milana,

Medica

for publication July 22, 1985. requests: Italy.

Maria

VI, ~Jniversitzi March Radice,

di Milam.

27, 1985; revision M.D.,

Via

received

L. Mumtori

June

26, 1985;

n. 29, 20135

role in the pathogenesis of hypertensi0n.l There is evidence that strains of rats prone to develop hypertension have a greater myocardial mass than do control rata before hypertensive levels are recorded.z-4In those strains the early stage of hypertension is represented by a hyperkinetic state consisting of an elevation in cardiac output with normal vascular peripheral resistance. 3s5 Some studies have also con115