Left Ventricular Function Before and After Reaching the Anaerobic Threshold

Left Ventricular Function Before and After Reaching the Anaerobic Threshold* Charles A Boucher, M.D., F.G.C.P.; Mark D. Anderson, M.D.; Michael S. Schneider, M.D.; Judith H. Murphy, M.D.; Robert D. Okada, M.D., F.C.C.P.; and David]. Kanarek, M.D.

Simultaneous pulmonary gas exchange analysis and exercise radionuclide angiography were performed in 24 normal patients (14 supine and ten upright). Left ventricular (LV) volumes and ejection fraction (EF) were measured at rest, anaerobic threshold (point of nonlinear increase in ventilation relative to oxygen uptake), and peak exercise. The anaerobic threshold occurred at a similar heart rate for supine vs upright exercise, 78 percent and 77 percent of peak heart rate, respectively. The anaerobic threshold occurred at a similar workload for supine vs upright exercise, 60 percent and 56 percent of peak workload, respectively. The anaerobic threshold also occurred at a similar oxygen uptake for supine vs upright exercise, 69 percent vs

69 percent of peak oxygen uptake, respectively. For both exercise modes, mean LVEF increased (p0.68). Therefore, for both supine and upright exercise, the major augmentation in LVEF occurs at earlier stages of exercise, prior to the anaerobic threshold. After the anaerobic threshold, the LVEF response may be highly variable, and a uniform increase is not necessarily expected even in normal subjects.

The exercise test is an important part of the evaluation of patients with cardiac and pulmonary diseases, because abnormalities not evident at rest may be unmasked. The development of exercise radionuclide angiography has expanded the diagnostic potential of exercise testing.':" Although several radionuclidederived parameters of global left ventricular (LV) function have been described, only the ejection fraction (EF) is widely utilized. Accordingly, an understanding of the EF response to exercise to be anticipated in normal subjects is important for the appropriate interpretation of individual results. An increase in LVEF ofO.05 or greater from rest to peak exercise or establishment of absolute lower limits of normal have been suggested as normal criteria. 2.3 However, rest and peak exercise values in normal subjects do not always meet either of these criteria. 14-16 Therefore, despite its widespread use, the definition of "normal' EF is uncertain. This is in part because exercise is a complex combination of increased contractile state, heart rate, and loading conditions, each of which may affect LVEF differently.":" Furthermore, most studies compare rest values to those at peak exercise effort and seldom consider the EF at another end-point of exercise, such as the anaerobic threshold. 23-25 In this study, the use ofupeak effort" as the endpoint

in normal subjects was examined. Radionuclide angiography was performed on normal subjects with simultaneous pulmonary gas exchange analysis to determine the timing of the anaerobic threshold. Ejection fraction values were studied at rest, at the anaerobic threshold, and at "peak" exercise and were related to end-diastolic and end-systolic volume changes during exercise. The data provide a better understanding of the spectrum of the normal LVEF response to exercise.

*From the Cardiac and Pulmonary Units, Massachusetts General Hospital, Boston. Supported in part by US Public Health Service Grant Number HL 21751 and HL 26215 and Training Grants HL 07354 and HL 07416 from the National Institutes of Health, Bethesda, Maryland. Manuscript received May 8; revision accepted August 3. Reprint requests: Dr. Boucher, Cardiac Unit, Massachusetts General Hospital, Boston 02114

METHODS

Patient Population Twenty-four subjects underwent exercise radionuclide angiography. All were referred for evaluation of a chest pain syndrome. No subject had clinical evidence of cardiopulmonary disease and all had less than 1 percent probability of having significant coronary artery disease by Bayesian analysis by virtue of normal exercise ECG and thallium-201 stress tests. 26 In 15 of the subjects, cardiac catheterization had been performed, and all 15 had normal coronary arteries (less than 25 percent diameter luminal narrowing) and normal left ventricular function by contrast ventriculography, None of the subjects was receiving any medication at the time of the study. None had evidence of mitral valve prolapse, hypertension, or hypertrophic cardiomyopathy.

Exercise Protocol Fourteen subjects exercised in the supine position and underwent equilibrium gated blood pool imaging. There were six women and eight men, ranging in age from 20 to 68 years (mean ± 1 SI) = 42 ± 13). These subjects exercised on an electronically-braked bicycle ergometer. Ten subjects exercised in the upright position and underwent first-pass radionuclide angiography. All ten were men, ranging in age from 34 to 53 years (mean 48 ± 5). These subjects exercised on an electronically-braked bicycle ergometer. The data in the two groups of patients were analyzed separately. CHEST / 87 / 2 / FEBRUARY, 1985

145

Table I-Exercise Performance in Ten Sedentary Normal Patients Undergoing Two Exercise Tests

Heart rate: rest AT Peak Workload (kpm/rnin): AT Peak Oxygen uptake (ml/kg/rnin): AT Peak

Supinet

Upright

p

75±9 146* ± 13 (80%) 183* ± 12

83± 19 165* ± 17 (88%) 187 ± 13

NS <0.05 NS

555± 142 (62%) 885*±18O

675± 237 (71%) 945* ±235

NS NS

21.5±4.7 (66%) 32.8* ±6.6

24.1±7.0 (68%) 35.7* ±9.2

NS NS

*p
Pulmonary Gas Exchange Data Analysis The pulmonary data were analyzed by an on-line computer, and oxygen uptake, carbon dioxide output, R value, minute ventilation, and the ventilatory equivalent for oxygen were calculated at 15second intervals, as previously reported. 17 The anaerobic threshold was determined by gas exchange criteria as the point of nonlinear increase in the ventilatory equivalent for oxygen, which has been previously associated with elevations in simultaneously obtained arterial lactate samples. 27 This point was determined as the consensus of two observers. The heart rate, blood pressure, workload, and oxygen uptake at rest, anaerobic threshold, and peak exercise were noted. The normal values in our laboratory for the timing of the anaerobic threshold are shown in Table 1. These were derived from ten other healthy sedentary volunteers studied twice several weeks apart using the same supine and upright exercise protocols as were used in the study patients. This group consisted of nine men and one woman, ages 18 to 38 years (mean = 27 ± 9). No radionuclide studies were performed in these patients. With supine exercise, the anaerobic threshold occurred at 80 percent of peak heart rate, 62 percent of peak workload, and 66 percent of peak oxygen uptake. With upright exercise, the anaerobic threshold occurred at 88 percent of peak heart rate, 71 percent of peak workload, and 68 percent of peak oxygen uptake. Although the mean anaerobic threshold and peak exercise values appeared to be higher with upright exercise, they were not significantly different except for the anaerobic threshold heart rate, which was higher with upright exercise (p
Badionuclide Data Acquisition Supine exercise multigated blood pool imaging was performed using 20 mCi technetium-99m in vivo labeled red blood cells. 8.28 Immediately prior to exercise, multigated cardiac image acquisition was performed in the anterior position and in the left anterior oblique projection that best visualized the interventricular septum

148

using an Anger gamma scintillation camera interfaced to an imaging computer. Two-minute cardiac collections were synchronized with the QRS complex of the ECG to obtain 14 frames per cardiac cycle. Two-minute left anterior oblique cardiac images were collected during the last two minutes of each three-minute workload. Upright exercise first pass radionuclide angiography was performed in the anterior projection. 13.1U8 A total of 7 mCi of technetium-99m pertechnetate was used for the first injection, and 9 and 13 mCi, respectively, for the two subsequent injections. The patients were pretreated with stannous pyrophosphate. The isotope was administered via an 18 gauge, two-inch intravenous cannula placed in an antecubital vein and flushed with 20 ml of saline solution. The images were processed using the standard computer and software. Images were acquired at .05 second intervals for 50 seconds following the injection at rest and at .025 second intervals for 25 seconds for the injections at exercise.

Badionuclide Data Analysis Left ventricular EF was measured at rest, at the anaerobic threshold, and at peak exercise from the gated blood pool and firstpass scans by two separate observers. For the equilibrium gated studies, the EF was determined from the left anterior oblique scan by a standard counts method.v" After background subtraction, the activity in the left ventricle throughout the cardiac cycle was derived using a semiautomated edge detection algorithm to determine the left ventricular borders in each frame. Ejection fraction was calculated from the difference between the background-corrected enddiastolic and end-systolic counts divided by the end-diastolic counts. Ejection fraction values were the mean of two determinations by each observer and the mean of the two observers' values was used in the data analysis. U sing area-length techniques, approximations of left ventricular end-diastolic volume were made at rest, at the anaerobic threshold and at peak exercise by two separate observers and the means utilized in the data analysis. For the gated equilibrium study, enddiastolic volume at rest was derived from the anterior and left anterior oblique views using a previously reported geometric biplane area-length method. 29 The volume was then determined using the left anterior oblique alone at rest, anaerobic threshold and peak exercise, and these three values were proportionately corrected by the comparative single plane and biplane values at rest, as previously reported. 15 For the first pass studies, the software of the System 77 was utilized. 30·31 A region of interest was manually placed over the left ventricle, and a time-activity curve was generated. The left ventricular activity peaks were considered the end-diastoles, and the valleys were considered the end-systoles. Only cycles with 70 percent or more of the maximum end-diastolic activity in the end-diastolic frame were included as left ventricular beats. Background was the activity within the left ventricular region of interest prior to the first left ventricular beat. The background subtracted left ventricular beats were summed to generate a representative cardiac cycle. Ejection fraction was end-diastolic minus end-systolic counts divided by end-diastolic counts in the representative cardiac cycle. In addition, the end-diastolic outline was analyzed for end-diastolic volume using a single plane area-length method. Although the first two first pass injections nearly always produced sufficient counts for data analysis, the third (peak exercise) first pass acquisition sometimes contained insufficient data for analysis after subtraction of the background that had accumulated after the first two injections. Only patients with peak end-diastolic counts in the representative cycle above 5,()()() were included. 31 This figure is based on previous studies which assessed the accuracy of volume measurements using this technique in relation to maximum counts. For both gated equilibrium and first pass methods, the EF and end-diastolic volume values were used to derive stroke volume and end-systolic volume. This eliminated geometric assumptions of the Left Ventricular Function and Anaerobic Threshold (Boucher st 8/)

Table 2-Anaeromc Threshold cs Peak LevellL-ith SupineExercise (n = 14)* Rest 69± 12§ Heart rate Workload (kpm/min) Oxygen uptake (mllkglmin) LV ejection fraction 0.66 ± .06t Relative LV volumes EDV 100 66±6t SV ESV 34±6t

Anaerobic Threshold

Peak

113± IS (78%)

(§)l4S:!: 18

438± 129 (60%)

(§)727± 202

14.7±4.2 (69%) 0.72±.OS

(§)21.3:!:3.8 O.71:!:.O8

99:!: 18 72±IS 27±6

107:!: 13 76± IS 31±8

·Values are mean ± 1 SD. Mean anaerobic threshold relative to peak exercise values are in parentheses. LV volumes are in milliliters relative to rest EDV =100 for all patients. tp
Statistical Methods All values were expressed as mean ± 1 standard deviation. Mean differences in the same patient were compared using a paired Students r-test, and mean differences in different patient groups were compared using a one-way analysis of variance followed by a Neuman-Keuls multiple comparison test.

anaerobic threshold (p<0.05), but there was no further change from anaerobic threshold to peak exercise. The EF values in the eight men were not different than those in the six women. The increase in EF and decrease in end-systolic volume prior to the anaerobic threshold was related to the rest EF value. In the nine patients with a rest EF below 0.68, mean EF increased by + .09± .03 from rest (0.62 ± .03) to anaerobic threshold (0.71 ± .05), p
Upright Exercise The data in the ten patients undergoing upright exercise are shown in Table 3. The anaerobic threshold occurred at 77 percent of peak heart rate, 56 percent of peak workload, and 69 percent of peak oxygen uptake. The occurrence of the anaerobic threshold was compa-

RESULTS

O 85

Supine Exercise The data in the 14 patients undergoing supine exercise are shown in Table 2. The anaerobic threshold occurred at 78 percent of peak heart rate, 60 percent of peak workload, and 69 percent of peak oxygen uptake, which was similar to the relative level at which the anaerobic threshold occurred in the normal volunteers (Table 1). However, this group was older than the volunteer group (p<. 01)and achieved a lower absolute heart rate, workload, and oxygen uptake at the anaerobic threshold and peak exercise than the healthy volunteers (p<0.05). The LVEF and relative volumes are shown in Table 2 and Figure 1. There was a significant increase in mean EF between rest and anaerobic threshold (p
SUPINE

080 0.75

~j::: ~

0.70

~

li:

~

065

I:::

~

l3

060 055 050

0= Mean Value

Rest

Anaerobic Peak Threshold Effort L- Exercise-1

FIGURE 1. Individual and mean left ventricular ejection fraction (LVEF) values for supine exercise are shown at rest. the anaerobic threshold and peak effort. The mean LVEF at rest (0.66± .06) increased to O.72:!: .OSat the anaerobic threshold (p
CHEST I 87 I 2 I FEBRUARY. 1985

147

Table 3-Anaerobic Thre.hold v. PeakLevel with Upright Exercise ("=10)* Rest Heart rate 78± 17 Workload (kpm/rnin) Oxygen uptake (ml/kg/min) LV ejection fraction 0.61 ± .06t Relative LV volumes EDV 100 SV 61±7t ESV 39±7t

Anaerobic Threshold

Peak

127± 14 (77%)

164± 14

450±80 (56%)

806± 137

19.5±3.4 (69%) 0.68±.06

28.2±5.1 0.69±.05

105±22 7l±8 34±9

107±27 73±15 34±15

*Values are mean ± 1SD. Mean anaerobic threshold relative to peak exercise values are in parentheses. LV volumes are in milliliters relative to rest EDV = 100 for all patients. tp
rable to the relative level at which the anaerobic threshold occurred in normal volunteers (Table 1). However, this group was older than the volunteer group (p<0.05) and achieved a lower absolute heart rate at the anaerobic threshold and at peak exercise than the healthy volunteers (p<0.05). The LVEF and relative volumes are shown in Table 3 and Figure 2. There was a significant increase in EF between rest and anaerobic threshold (p
UPRIGHT

075

~

0.70

~

0.65

li:

~

0.60

~ ~

0.55

i:::

0

O=MeanValue

050 0.45

Rest

Anaerobic Threshold ~

Peak Effort

Exercise-..l

FIGURE 2. Individual and mean left ventricular ejection fraction (LVEF) values for upright exercise are shown at rest, the anaerobic threshold and peak effort. The mean LVEF at rest (0.61 ± .06) increased to 0.68 ±.06 at the anaerobic threshold (p
148

DISCUSSION

These data are consistent with previous studies that have examined the change in LVEF and volumes from rest to peak exercise.v" In most normal subjects, EF increases from rest to peak effort for both supine and upright exercise. This is a result ofan increase in stroke volume and a decrease in end-systolic volume with little or no change in end-diastolic volume. Preload compensation, and the Starling mechanism (a parallel increase in stroke volume and end-diastolic volume) occurred in some patients, but not in either group as a whole. 33.34 In patients with a high rest value (above0.68 in this study), there was no increase in EF above the rest value during exercise and no decrease in endsystolic volume during exercise. Such patients may already have augmented contractile response at rest and may be unable to increase contractility with exercise. Ejection Fraction Changes and the Anaerobic Threshold

~

(..)

and the anaerobic threshold, there was a significant increase in stroke volume, decrease in end-systolic volume, and no change in end-diastolic volume. Between the anaerobic threshold and peak exercise, there was no further change in ventricular volumes. The increase in EF from rest to anaerobic threshold was related to the rest value. In the seven patients with a rest EF below 0.68, the mean increase in EF (+ .09± .05), p
In addition to studying the changes in left ventricular performance from rest to peak exercise, we also evaluated the changes before and after the anaerobic threshold. The anaerobic threshold is considered the work level at which lactic acid accumulates in the blood due to a shift to anaerobic metabolism in the working muscles. This shift is a result of an inadequate peripheral oxygen delivery, and therefore reflects overall cardiovascular capacity. We measured the anaerobic threshold by pulmonary gas-exchange analysis as the nonlinear increase in the ventilatory equivalent for oxygen (VErV02) . This hyperventilatory response occurs as a result of the excess carbon dioxide generated by the buffering oflactic acid by the sodium bicarbonate system in the blood. In both our normal volunteers and study patients, the anaerobic threshold occurred at about 55 percent to 70 percent of the peak workload. For supine or upright exercise, there is a consistent augmentation in EF before the anaerobic threshold at Left Ventricular Function and Anaerobic Threshold (Boucher et aI)

earlier stages of exercise; whereas after the anaerobic threshold, the EF response is variable and there is normally no consistent increase. Although no previous studies have examined ejection fraction changes before and after the anaerobic threshold, several have examined EF at an arbitrary submaximal exercise level, usually about half of the peak level. 5-; These data agree that most of the increase in EF occurs at the early stages of exercise, but show conflicting data about whether further augmentation occurred at higher levels. However, it is possible that the submaximal level in other studies was below the anaerobic threshold. These studies are also consistent with previous hemodynamic studies demonstrating that most of the increase in stroke volume occurs at the earlier stages of exercise. 18.35-3; There are two possible interpretations of the difference in the EF change before and after the anaerobic threshold. One is that they are related, and the other is that they are coincidental. It is possible that when LV stroke volume reaches a peak, that this is somehow reflected in oxygen delivery to the working muscles, and there is a shift to anaerobic metabolism to meet energy needs. It is also possible that the lactic acid accumulation has an adverse impact on the myocardium, so that no further augmentation of EF is possible. We have not demonstrated any evidence to support a relationship between anaerobic threshold and the maximal EF response. Instead, our observation is probably coincidental in that the LV response to exercise utilizes most of the compensatory mechanisms (preload, contractility) at the lower early work levels and that there is little further augmentation at higher levels. At higher heart rates, there is dramatic shortening of diastole, which could limit or decrease any further preload compensation, and thereby, the stroke volume response of the left ventricle. Unfortunately, our data are unable to resolve this issue.

Potential Limitations of the Study Our normal subjects were patients referred for exercise testing for a chest pain syndrome, some of whom underwent cardiac catheterization. Sometimes, this subset may not be truly normal and the failure of EF to increase after the anaerobic threshold in our patients may reflect some subclinical cardiac disease, which may not be present in truly normal subjects. However, our findings are part of the spectrum of patients free of coronary disease and may in part explain the reduced specificity of the exercise EF response that has been seen in this setting. 14-16 It would be interesting to try to confirm our observations in young healthy normal volunteers, but this was not performed. There are theoretical objections to using a radionuclide area-length approach to measure ventricular

volumes. However, we and others have used this previously and found it satisfactory. 15,30.31 In particular, the use of single plane anterior view first pass analysis may be questioned. However, our patients had normal wall motion and were free of the regional changes that could distort left ventricular geometry in an asymmetric manner and that would lead to the need for a biplane analysis. In addition, we used a geometric approach to measure end-diastolic volume only, and the shape of the left ventricle tends to remain elliptical at end-diastole. End-systolic volume was derived from the end-diastolic volume and EF: In addition, the observer variability in the area-length volume method may be substantial and may approach the relatively small changes observed in ventricular volumes with exercise in individual patients. For this reason, we analyzed only relative changes and mean group differences. The significant differences in group means analyzed in our study should not be produced by random individual variability.

Clinical Implications During supine or upright exercise radionuclide angiography, the normal EF increase occurs primarily because of a reduction in end-systolic volume. In patients with a high EF at rest, there is little or no further increase in EF with exercise. When the EF increases, it occurs consistently before the anaerobic threshold, but after the anaerobic threshold, the response is variable. The anaerobic threshold is a marker of the point during exercise when an increase in EF above the rest value is anticipated. We do not suggest that exercise test should be terminated at this point, particularly in patients with chest pain in whom ischemia may be provoked only at peak exercise. However, this study has potential implications for exercise radionuclide angiography. Image quality is sometimes limited at peak effort because of excessively high heart rates and increased motion of the patient with labored breathing and with the patient struggling to continue pedaling. Our data suggest that images acquired just below the peak in the interval between the anaerobic threshold and peak also reasonably represent LV function at maximal or near maximal stress. Higher quality and more reliable quantitative information derived from images at such a submaximal level may be preferable to that derived from lower quality images at peak effort. ACKNOWLEDGMENTS: The authors appreciate the secretarial assistance of Janice Cahill and the technical assistance of Barry Callahan, Gerard Cotter, Maureen McCarthy, Olivia Reeney, and William Shea.

REFERENCES 1 Marshall RC, Berger HJ, Costlin JC, Freedman GS, Wolberg J, Cohen LS, et al. Assessment of cardiac performance with quantitative radionuclide angiocarrdiography: sequential left ventricuCHEST / 87 / 2 / FEBRUARY, 1985

149

lar ejection fraction, normalized left ventricular ejection rate, and regional wall motion. Circulation 1977; 56:820-29 2 Borer JS, Kent KM, Bacharach SL, Green MV, Rosing DR, Seides SF, et al. Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with coronary artery disease: comparison with exercise electrocardiography. Circulation 1979; 60:527-80 3 Borer JS, Rosing DR, Kent KM, Bacharach SL, Green M~ Mcintosh CJ, et ale Left ventricular function at rest and during exercise after aortic valve replacement in patients with aortic regurgitation. Am J Cardiol 1979; 44:1297-1304 4 Okada RD, Pohost GM, Kirshenbaum HD, Kushner FG, Boucher CA, Block PC, et ale Radionuclide determined change in pulmonary blood volume with exercise: improved sensitivity of multigated blood pool scanning in detecting coronary artery disease. N Engl J Med 1979; 301:569-76 5 Slutsky R, Karliner J, Ricci D, Schuler G, Pfisterer M, Peterson K, Ashburn \V. Response of left ventricular volume to exercise in man assessed by radionuclide equilibrium angiography. Circulation 1979; 60:565-71 6 Brady TJ, Thrall ]H, Lo K, Pitt B. The importance of adequate exercise in the detection of coronary heart disease by radionuelide ventriculography. J Nuc1 Med 1980; 21:1125-30 7 Poliner LR, Dehmer GJ, Lewis SE, Parkey RW, Blomqvist CG, Willerson J1: et ale Left ventricular performance in normal subjects: a comparison of the responses to exercise in the upright and supine positions. Circulation 1980; 62:528-34 8 Okada RD, Kushner FG, Kirshenbaum HD, Strauss HW, Dunsmore RE, Newell JB, et ale Interobserver and intraobserver variance in the evaluation of left ventricular regional wall motion and ejection fraction using contrast ventriculogram and rest and exercise multigated blood pool image. Circulation 1980; 61: 128-36 9 Slutsky R. Response of the left ventricle to stress: Effects of exercise, atrial pacing, afterload stress and drugs. Am J Cardiol 1981; 47:357-64 10 Berger HJ, Sands MJ, Davies RA, Wackers FJ Th, Alexander J, Laschman AS, et al. Exercise left ventricular performance in patients with chest pain, ischemic-appearing exercise electrocardiograms, and angiographically normal coronary arteries. Ann

11

12

13

14

15

16

17

Intern Med 1981; 94:180-91 Dehmer GJ, Firth BG, Hillis LD, Corbett JR, Lewis SE, Parkey RW, et ale Alterations in left ventricular volumes and ejection fraction at rest and during exercise in patients with aortic regurgitation. Am J Cardioll981; 48:17-27 Iskandrian AS, Hakki A, Kane SA, Segal BL. Quantitative radionuclide angiography in assessment of hemodynamic changes during upright exercise: observations in normal subjects, patients with coronary artery disease and patients with aortic regurgitation. Am J Cardio11981; 48:239-46 Gibbons RJ, Lee KL, Cobb F, Jones JH. Ejection fraction response to exercise in patients with chest pain and normal coronaryarteriograms. Circulation 1981; 64:952-57 Gibbons RJ, Lee KL, Cobb FR, Coleman RE, Jones RH. Ejection fraction response to exercise in patients with chest pain, coronary artery disease and normal resting ventricular function. Circulation 1982; 66:643-48 Osbakken MD, Boucher GA, Okada RD, Bingham JB, Strauss HW, Pohost GM. Spectrum of global left ventricular responses to supine exercise: limitation in the use of ejection fraction in identifying patients with coronary artery disease. Am J Cardiol 1983; 51:28-35 Rozanski A, Diamond GA, Berman D, Forrester JS, Morris D, Swan HJC. The declining specificy of exercise radionuclide ventriculography. N Eng} J Med 1983; 309:518-22 Boucher CA, Kanarek DJ, Okada RD, Hutter AM Jr, Strauss

150

. 18

19

20 21

22 23

24 25 26

27

28

29

HW, Pohost GM, et ale Exercise testing in aortic regurgitation: comparison of radionuclide left ventricular ejection fraction with exercise performance at the anaerobic threshold and at peak exercise. Am J Cardiol 1983; 52:801-08 Manyari DE, Kostuk WJ. Left and right ventricular function at rest and during bicycle exercise in the supine and sitting positions in normal subjects and patients with coronary artery disease: assessment by radionuclide ventriculography. Am J CardioI1983; 52:36-42 Vatner SF, Pagani, M. Cardiovascular adjustments to exercise hemodynamics and mechanisms. Prog Cardiovasc Dis 1976; 19: 91-108 Krayenbuehl H~ Hess OM, Turina J. Assessment of left ventricular function. Cardiovasc Med 1978; 3:883-908 Kreulen TH, Bove AA, McDonough M1: Sands MJ, Spann JF: The evaluation of left ventricular function in man. Circulation 1975; 51:677-88 Mason D1: Regulation of cardiac performance in clinical heart disease. Am J Cardio11973; 32:437-48 Wasserman K, McIlroy MB. Detecting the threshold of anaerobic metabolism in cardiac patients during exercise. Am] Cardiol 1964; 14:844-52 Davis JA, Vodak ~ Wilmore JH, Vodak J, Kurtz ~ Anaerobic threshold and maximal aerobic power for three modes of exercise. J Appl Physiol1976; 41:544-50 Wasserman K. Dyspnea on exertion: Is it the heart or the lungs? JAMA 1982; 248:2039-43 Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of conronary artery disease. N Engl ] Med 1979; 300: 1350-58 Yeh M~ Gardner RM, Adams TD, Yanowitz FG, Crapo RO. Anaerobic threshold: problems of determination and validation. J Appl Physioll983; 55:1178-86 Kaul S, Boucher CA, Okada RD, Newell JB, Strauss HW, Pohost GM. Sources of variability in the radionuclide angiographic assessment of ejection fraction. Am J Cardiol 1984; 53:823-28 Boucher CA, Bingham JB, Osbakken MD, Okada RD, Strauss HW, Block PC, et ale Early changes in left ventricular size and function following correction of left ventricular volume overload. Am

J Cardiol

1981; 47:991-1004

30 Scholz PM, Rerych SK, Moran ]F, Newman GE, Douglas JM, Sabiston DC Jr., et ale Quantitative radionuclide angiography. Catheter Cardiovasc Diag 1980; 6:265-83 31 Anderson PAW, Rerych SK, Moore TE, Jones RH. Accuracy of left ventricular end-diastolic dimension determinations obtained by radionuclide angiocardiography. J Nucl Med 1981; 22:500-05 32 Boucher CA. Radionuclide assessment of ventricular function. In: Morganroth J, Parisi AF, Pohost GM, eds. Noninvasive cardiac imaging. Chicago: Year Book Medical Publishers, Inc, 1983:71-87 33 Rankin LS, Moos S, Grossman W Alterations in preload and ejection phase indices of left ventricular performance. Circulation 1975; 51:910-15 34 NixonJ~ MurrayRG, LeonardPD, MitchellJH, BlomqvistCG. Effect of large variations in preload on left ventricular performance characteristics in normal subjects. Circulation 1982; 65: 698-703 35 Ross J Jr, Gault JH, Mason D1: Linhart JW, Braunwald E. Left ventricular performance during muscular exercise in patients with and without cardiac dysfunction. Circulation 1966; 34: 597-608 36 Astrand PO, Rodahl K. Textbook of work physiology, 2nd ed. New York: McGraw-Hili Book Co, 1977:186-89 37 Thadani U, Parker J. Hemodynamics at rest and during supine and sitting bicycle exercise in normal subjects. Am J Cardiol 1978; 41:52-60

Left Ventricular Functionand AnaerobicThreshold (Boucher et 8/)