Download Normal Exercise Capacity in Patients with Severe Left Ventricular

Normal Exercise Capacity in Patients
with Severe Left Ventricular Dysfunction:
Compensatory Mechanisms
ROBERT L. LITCHFIELD, D.O., RICHARD E. KERBER, M.D., J. WILLIAM BENGE, M.D.,
ALLYN L. MARK, M.D., JOSEPH SOPKO, M.D., RANBIR K. BHATNAGAR, PH.D.,
AND MELVIN L. MARCUS, M.D.
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SUMMARY About one-third of patients who have severe left ventricular dysfunction can achieve normal
levels of exercise. To elucidate the mechanisms that permit this to occur, we studied six patients with severe
left ventricular dysfunction (average left ventricular ejection fraction 17
2.5% [mean ± SEM]) who
achieved nearly normal levels of exercise tolerance (greater than 11 mhutes of treadmill exercise, Sheffield
protocol). All patients had normal pulmonary function at rest and during exercise. Hemodynamics were
measured at rest and during supine and upright exercise. The major mechanisms of the preserved exercise
capacity in these patients were chronotropic competence, ability to tolerate elevated wedge pressures (33 +
3 mm Hg) without dyspnea, ventricular dilation, and increased levels of plasma norepinephrine at rest and
during exercise. Also, whereas peripheral vascular resistance was unchanged during supine exercise, it
decreased by 50% during similar levels of upright exercise. As a consequence, increases in cardiac output
from rest to exercise were greater during upright than supine exercise (100% vs 50%, respectively) (p <
0.05), and pulmonary wedge pressures were lower during upright than supine exercise (21 ± 5 mm Hg vs 33
+ 3 mm Hg). Thus, multiple mechanisms permit some patients with severe left ventricular dysfunction to
achieve normal levels of exercise. These studies emphasize that left ventricular function must be assessed by
direct means rather than inferring function of the left ventricle from the results of an exercise tolerance test.
A PREVIOUS STUDY from our laboratory' showed
that exercise capacity in patients with severe left ventricular dysfunction varies widely. There are two major weaknesses in previous studies of exercise hemodynamics in patients with heart disease-. First, the
patient populations have usually-not been homogeneous with regard to the severity of their cardiac dysfunction.2-9 Second, in most studies, only a few aspects of
cardiac function have been examined,2-9 and the hemodynamic measurements were obtained with patients
either in the supine or upright position.>6' 8-10
We studied patients with severe left ventricular dysfunction and normal exercise tolerance to determine
the compensatory mechanisms that allowed them to
achieve normal exercise levels. The patients were
studied in both the supine and upright positions.
were being treated for congestive heart failure at the
time of our study; all six patients were taking digitalis
preparations and four were taking diuretics. All patients were on a salt-restricted diet. Patients with valvular heart disease, arrhythmias, or noncardiac disabilities that limit exercise were excluded. Approval of
the protocol was obtained from the Human Use Committee of the University of Iowa, and each patient gave
informed consent.
Graded Treadmill Exercise Test
All patients underwent physician-monitored graded
treadmill exercise tests using the Sheffield modification of the Bruce protocol." A multilead ECG (12
standard leads and Frank X, Y, and Z leads) and cuff
blood pressure were measured every 3 minutes during
exercise. The exercise test was terminated if the patient
complained of marked dyspnea or fatigue or achieved
85% of the maximal predicted heart rate.
Materials and Methods
Patients
We studied six males (mean age 60 years, range 5369 years) who had left ventricular ejection fractions
less than 30% by gated isotope ventriculograms (range
7-25%) and nearly normal exercise tolerance by graded treadmill exercise test. Four patients had coronary
artery disease and two had congestive cardiomyopathy. All of the coronary patients had evidence of
previous infarction, but none had angina. All patients
Pulmonary Function Tests
Pulmonary function testing was performed and respiratory volumes were measured. In addition, two
types of exercise pulmonary functions were determined in each patient.'2 The first was a progressive
upright bicycle test with an initial power output of 100
kpm/min. Each minute, the work load was increased
by 100 kpm/min while a physician monitored the
ECG, cuff blood pressure and ventilation. Oxygen
consumption and carbon dioxide production were
measured with oxygen and carbon dioxide analyzers
after each minute of exercise. Exercise was terminated
if the patient complained of significant dyspnea or
fatigue. A second pulmonary exercise test was performed on a different day. Measurements were obtained at one-third and two-thirds maximal exercise
(based on external load) in the upright posture. Each
From the Cardiovascular and Clinical Research Centers and the Departments of Internal Medicine and Pharmacology, University of Iowa
and Veterang Administration Hospitals, Iowa City, Iowa.
Supported by Research Career Development Award HL-00328, Program Project grant HL- 14388, and grant RR059 from the General Clinical Research Center Program, Division of Research Resources, NIH.
Address for correspondence: Melvin L. Marcus, M.D., Department
of Internal Medicine, University of Iowa Hospitals, Iowa City, Iowa
52242.
Received April 16, 1981; revision accepted October 28, 1981.
Circulation 66, No. 1, 1982.
129
130
VOL 66, No 1, JULY 1982
CIRCULATION
level of exercise was continued for more than 3 minutes. Oxygen and carbon dioxide consumption, heart
rate, brachial artery pressure, pulmonary artery pressure and mean pulmonary arterial wedge pressure were
obtained at each level of exercise.
Hemodynamic Monitoring
Pulmonary wedge pressures and pulmonary artery
pressures were obtained using a #7F Swan-Ganz thermodilution catheter. Arterial pressure was monitored
by inserting a straight, 20-cm #5F catheter into the
brachial artery. Heart rate and rhythm were recorded
by a standard 12-lead ECG and cardiac output
was determined by the thermodilution'3 and Fick14
methods.
Norepinephrine Levels
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Arterial blood samples were drawn and packed in
dry ice for later determinations of norepinephrine levels using a modification of a method described by de
Champlain et al. 15 One sample was obtained at rest and
another at two-thirds maximal supine exercise.
Cardiac Imaging
Gated isotope ventriculograms were taken at rest
and two-thirds maximal supine exercise in all patients.
Red cells labeled in vivo with technetium-99m were
used as the imaging agent. A small-field-of-view portable gamma camera with an all-purpose collimator
(energy window 140 KeV and width ± 20%) was used
to obtain the images, which were recorded on a computer. A time-activity curve composed of 16 frames
(200,000 counts/frame) was obtained both at rest and
during exercise in the 450 left anterior oblique projection. Rest and exercise left ventricular ejection fractions were calculated from the left anterior oblique
projection using a method described by Burow et al.'6
No significant ectopy was noted during acquisition.
Echocardiograms
Echocardiograms were performed at supine rest
using an M-mode ultrasonoscope and a 2.25-MHz
transducer focused at 7.5 cm. Recordings were made
on a strip-chart recorder. Left ventricular end-diastolic
dimensions were measured at a level immediately below the mitral valve.17 End-systolic dimensions and
ejection fraction measurements were not made from
the echocardiograms, as they may be unreliable in
patients with ischemic heart disease.
Protocol
Upon admission, each patient related a complete
medical history. Treadmill exercise tolerance tests
done at least 1 week before the study suggested that the
patients' exercise tolerance was better than expected.
A physical examination, chest x-ray and echocardiogram were performed, and a complete blood count,
blood urea nitrogen, serum creatinine, sodium, potassium, chloride and bicarbonate were obtained. A practice session was held for each type of exercise (supine
and upright) to familiarize the patients with the exercise procedure and the apparatus used to collect ex-
pired pulmonary gases. During this practice session,
we determined the maximal level of exercise that each
patient could achieve in the supine and upright postures. Submaximal levels of exercise (one-third and
two-thirds maximal) were used to ensure steady-state
conditions (more than 3 minutes of continuous exercise at one work load) during hemodynamic measurements. Isotope ventriculograms were also taken on day
1 at rest and at two-thirds maximal exercise.
On day 2, the patients were taken to the catheterization laboratory where Swan-Ganz and arterial catheters were placed through a right antecubital cutdown.
A plethysmograph was placed on the left arm to measure forearm blood flow. 18 All measurements were obtained at supine rest and, after the third minute, at onethird and two-thirds maximal steady-state exercise.
The patient was allowed to recover for 15-45 minutes
before the upright exercise tests. Samples were again
obtained at upright rest and at one-third and two-thirds
maximal steady-state exercise. After the upright exercise studies, the catheters were removed and the skin
was sutured. On day 3, a graded treadmill exercise test
was performed.
Calculations and Statistical Analysis
Peripheral vascular resistance was calculated as
80 * MAP/CO, where MAP = mean arterial pressure
and CO = cardiac output. Forearm vascular resistance
was calculated as MAP/FBF, where FBF = forearm
blood flow.
Differences between various treatments were determined by paired t test or analysis of variance. The
significance of subgroup differences were assessed
with Duncan's test.19 Results are presented as mean
+ SEM.
Results
Clinical Examination
All patients had a history of congestive heart failure.
At the time of our study, none of the patients had
physical findings (peripheral edema, increased systemic venous pressure, tachycardia or a third heart
sound) or symptoms (dyspnea at rest or upon exertion)
of advanced heart failure. Two patients had a 2/6 murmur of mitral regurgitation. The cardiothoracic ratio
by chest x-ray averaged 0.54 + 0.02, and there was no
evidence of marked congestion or pleural effusion.
The hemoglobin concentration (15.1 + 0.2 g/dl),
blood urea nitrogen (18.6 + 2.7 mg/dl), and other
blood chemistries were nornal. Thus, the patients in
this study had clinically compensated cardiac failure.
Graded Exercise Tolerance Test
All patients exercised for at least 12 minutes on the
treadmill (Sheffield protocol"). The average duration
of treadmill exercise was 13.3 + 0.7 minutes, and the
maximal heart rate averaged 146 + 11 beats/min.
Pulmonary Function Test
No patient had evidence of limiting pulmonary disat rest or during exercise testing (table 1). During
supine or upright exercise, oxygen consumptions and
ease
EXERCISE CAPACITY IN SEVERE LV DYSFUNCTION/Litchfield et al.
TABLE 1. Results of Pulmonary Function Test
FVC (1)
FEV1
Maximal exercise
Work load (kpm/min)
Heart rate (beats/min)
Mean arterial pressure (mm Hg)
Oxygen consumption (mi/kg/min)
Two-thirds maximal exercise
Arterial Po2 (mm Hg)
4.2±0.4
(97 ± 6%)*
(77±5.1%)*
650 ±56
148 ± 11
(87 ± 6%)*
112 ±6
19.1± 1.2
(71 ± 3%)*
87±5
(94 ± 6)t
Arterial PcO2 (mm Hg)
Arterial pH
V02/pulse
VE/V02
34.5 ±2
(30.3 ± 2)t
7.42 ±0.01
(7.49 ± 0.02)t
10±1
(1I±1)T
33± 1.9
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(27 ± 3)t
*Percent predicted.
tValue at rest.
tNormal value from Sheffield."
Abbreviations: FVC = forced vital capacity; FEV, = forced
expiratory volume in 1 second; kpm = kilopond meters; V02 =
oxygen uptake; VE = ventilatory equivalent; Po2 = oxygen tension; PcO2 = carbon dioxide tension.
pulmonary artery saturations were similar in all patients. The oxygen consumptions were similar to predicted values for two-thirds maximal oxygen consumption in normal age- and sex-matched subjects
(table 2).
Left Ventricular Function
Our patients' left ventricular ejection fractions were
severely depressed at rest and did not increase with
exercise (table 2). Left ventricular end-diastolic dimension assessed by M-mode echocardiography was 7
+ 0.4 cm (normal range 3.5-5.7 cm).17
Catecholamines
Norepinephrine levels were above normal at rest and
increased markedly with exercise (table 2).
Hemodynamics
Rest and two-thirds maximal exercise hemodynamics are reported for all patients (table 2, fig. 1). Resting
heart rate was nearly normal and increased appropriately with both supine and upright exercise. Cardiac
output at rest in the supine and upright positions was
normal. With exercise, cardiac output increased by
almost 50% in the supine position and by more than
100% in the upright position. During exercise,
changes in wedge pressure were marked. With supine
exercise, for example, wedge pressure averaged about
35 mm Hg. Stroke volume decreased slightly during
supine exercise, but increased by about 100% during
upright exercise.
Total peripheral vascular resistance changed little in
the supine position, but forearm vascular resistance
during supine exercise increased significantly. In the
upright posture, peripheral vascular resistance decreased by 50% during exercise.
131
Discussion
We previously reported a poor correlation between
left ventricular function assessed by left ventricular
ejection fraction and exercise tolerance determined by
a graded exercise test. The present study indicates that
the primary mechanisms that influence exercise capacity are (1) the ability to tolerate very elevated pulmonary artery wedge pressures without symptoms, (2)
preserved chronotropic response to exercise, (3) ventricular dilation, (4) augmented stroke volume and decreased peripheral vascular resistance with upright exercise, (5) increased cardiac output particularly with
upright exercise, and (6) increased levels of circulating
catecholamines at rest and during exercise.
Compensatory Mechanisms
Tolerance of High Pulmonary Wedge Pressures
During supine exercise, wedge pressures increased
to levels that frequently produced pulmonary edema.
However, even with pulmonary wedge pressures that
averaged 33 mm Hg, no patient had clinical signs of
pulmonary edema and none was limited by dyspnea
during exercise. Only fatigue prevented additional exercise. Two mechanisms could have permitted our patients to tolerate the abnormally high pulmonary venous pressures: increased pulmonary lymphatic flow,
which allows accelerated fluid removal,22 and chronic
changes in capillary walls, which inhibit transudation
of fluid into the interstitial space. Studies in animals
suggest that increased pulmonary lymphatic flow is
probably the major factor.
Chronotropic Competence
Impaired chronotropic response to exercise has been
implicated as contributing to the inability of patients
with cardiac failure to perform normal levels of exercise.23 Compared with age-matched controls, our patients showed normal heart rate response at two-thirds
maximal exercise (fig. 1, table 1). Thus, a normal
chronotropic response to exercise contributed to our
patients' exercise tolerance.
Ventricular Enlargement
All but one patient had an abnormally large left
ventricular diameter by echocardiography. Three of
the six patients had a cardiothoracic ratio greater than
0.5 by chest x-ray. Because stroke volume increases as
the ventricle dilates, even if fractional shortening remains constant, ventricular dilation was an important
compensatory mechanism in our patients.
Stroke Volume
In normal subjects, the contribution of changes in
stroke volume to changes in cardiac output during exercise has been carefully examined. Thadani and Parker21 showed in normal males (mean age 46 years) that
stroke volume changed little during supine submaximal exercise, but increased by 67% during upright
exercise. The results in our patients with severe left
ventricular dysfunction are similar to those reported by
Thadani and Parker in normal subjects. Stroke volume
132
VOL 66, No 1, JULY 1982
CIRCULATION
TABLE 2. Hemodynamic Responses During Supine and Upright Exercise
Supine
2/3 maximal
exercise
Rest
17 ± 2
15 ± 3
Ejection fraction (%)
(64 ± 2)19*
Cardiac index (t/m2)
2.95 ± 0.3
(3.5 ± 0.3)20
Heart rate (beats/min)
Mean arterial pressure (mm Hg)
68 ± 6
(73 ± 4)20
45 ± 6
(50 + 5)20
81 ± 5
Systemic vascular resistance
(dyn/sec/cm)
Pulmonary artery saturation (%)
1115 ± 163
(- 1220)20a
69 ± 1
Stroke index (mI/m2)
(96 ± 3)20
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Pulmonary wedge pressure (mm Hg)
(-69)5a
15 ± 4
Pulmonary artery pressure (mm Hg)
(6 ± 1)20
22 ± 4
(13 + 1)20
02 consumption (ml/kg/min)
3 ±0.4
(-3.5)12
Serum catecholamines (ng/ml)
Rest
Upright
2/3 maximal
exercise
(71 ± 2)'9
4.3 ± 0.31t
(7.7 ± 0.5)20
2.8 ± 0.3
(2.8 ± 0.2)20
5.9 ± 0.6tt
(7.3 ± 0.5)20
114 ± 9t
(128 ± 6)20
39 ± 3
(61 ± 6)20
107 ± 6t
(119 ± 4)20
1060 ± 125
(-685)20a
35 ± 2t
78 ± 6
(84 ± 4)20
32 ± 5
(35 ± 3)20
90 ± ST
(99 ± 4)20
1619 ± 207T
(- 1570)20a
55 ± 5
130 I I t:
(146 + 7)20
47 7
(52 + 5)20
109 + 7t
(121 ± 5)20
783 ± 141 t
(-740)20a
36 ± It
(-40)5a
(69)5a
5 ± 2t
(4 ± 1)20
17 ± 3
33 ± 3t
(13 ± 1)20
47 ± 4
(24 ± 2)20
12.5 ± 1.5t
(-1)12
(13 ± 1)20
4 ± 0.3
(-3.5)12
(-40)5a
20 ± 5t+
(8 ± 1)20
32 ± 7t+
(22 ± 2)20
16 ± 1.4tt
(-15)12
0.47 ± 0.18
1.4 ± 0.54
(0.46 ± 0.05)2
26 ± 7
35 ± 4
Forearm vascular resistance (mm Hg/ml)
(25 ± 11)'7
(35 ± 11)17
Mean arterial pressure (ml/min x 100 g)
*Values in parentheses are the normal values. The superscript number is the number of the reference that served as the
source for these values. An "a" following the superscript reference number indictes that the value was estimated from
data given in that reference.
tp < 0.05 vs value during same posture at rest.
tp < 0.05 vs value during same condition supine.
(0.28 ± 0.05)2
changed little during supine exercise, but increased by
62% during upright exercise. Thus, an increase in
stroke volume during upright exercise contributed to
the increase in cardiac output achieved by our patients.
Studies in patients with heart failure usually have not
included measurements of stroke volume during both
supine and upright exercise.
4Anrt
loo _
beats/
min
atia
7.5 r-
toL
5.0
Upright
50*
o- -o Suplne
_
50
Peripheral Vascular Resistance
Vascular resistance in nonexercising skeletal muscle
normally increases during exercise. 8 This also occurred in our patients with heart failure. In patients
with heart failure, vasodilation is limited during exercise.6'24 In our patients, total systemic vascular resistance did not change during supine exercise, but de-
Cardiac in dex
i/M2
2.5
0.0
Nedge
Systemic Vascular
2000
_
Resistance
Ire +
40
'_
dynes/
mmHg 20
sec/ 1000
cm
0
o
Rest
Exercise
Rest
Exercise
FIGURE 1. Hemodynamics during supine and
upright exercise. During upright exercise, systemic vascular resistance and pulmonary
wedge pressure are lower and cardiac index is
higher than during supine exercise. *p < 0.05
vs rest; + p < 0.06 vs value in the opposite
posture (rest or exercise).
EXERCISE CAPACITY IN SEVERE LV DYSFUNCTION/Litchfield et al.
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creased significantly during upright exercise. With
upright exercise, the magnitude of the decrease in total
systemic vascular resistance was similar to that in normal subjects performing similar levels of exertion
(table 2).
Why did total systemic vascular resistance decrease
during upright exercise and not change during supine
exercise? During exercise, the response of the total
systemic vascular resistance represents a balance between metabolic vasodilation in exercising muscle and
reflex vasoconstriction triggered by somatic afferents.
Normally, inhibitory cardiac afferents modulate the
reflex vasoconstriction triggered by muscular exercise
and somatic pressor reflexes.24' 25 As a result, total systemic vascular resistance decreases during exercise because metabolic vasodilation in exercising muscles
predominate. However, cardiac afferent input is impaired in patients with heart failure. This would be
expected to augment the somatic pressor vasoconstrictor reflex and thereby limit decreases in total systemic
vascular resistance during exercise. This could explain
the failure of total systemic vascular resistance to decrease during supine exercise in patients with heart
failure.
How could the cardiac afferents contribute to a significant decrease in total systemic vascular resistance
during upright exercise? Normally, cardiac afferent
input decreases during upright tilt because cardiac filling pressures and volume decrease.25 Consequently,
with exercise, the percent change in cardiac dimensions is increased relative to that during supine exercise. This greater change in cardiac dimensions may
help activate the cardiac afferent sensory endings,
which discharge during systole with a frequency that
depends largely on the mechanics of ventricular contraction. It is difficult to prove that this hypothesis
explains the mechanism for the restoration of the vasodilator response to exercise in the upright position in
patients with heart failure. The important point is that
the normal decrease in vascular resistance during upright exercise in patients with heart failure may contribute to the increase in stroke volume and preservation of exercise capacity in these patients.
Cardiac Output
An inadequate cardiac output response to exercise is
a common characteristic of patients in heart failure.4 1" 7-9 Our patients, although unable to increase
cardiac output to normal levels with exercise, doubled
their cardiac output with upright exercise. Increases in
cardiac output during supine exercise were more limited. These differences in exercise cardiac output during
supine and upright exercise are probably modulated by
significant differences in peripheral vascular resistance
that occurred during these two states.
Plasma Norepinephrine
Plasma norepinephrine levels were above normal at
rest and increased substantially during exercise. This
increase in catecholamines has also been reported by
133
Chidsey et al.,2 and is a significant compensatory
mechanism in patients with left ventricular dysfunction.
Advantages and Problems of the
Experimental Design
There are several advantages to our experimental
design. The patients were similar with respect to the
severity of left ventricular dysfunction and exercise
tolerance. In addition, no patient was accepted into the
study if exercise performance was limited by pulmonary disease or other noncardiac factors. Each patient
was familiarized with the supine and upright exercise
procedures. Maximal exercise was determined to calculate the two-thirds maximal exercise level. All measurements were obtained in the steady state so as to
eliminate dynamic variations seen with progressive exercise. Invasive hemodynamic monitoring was performed in both the supine and upright postures. Measurements of oxygen consumption and pulmonary
artery saturation indicate that during upright and supine exercise, comparable levels of cardiovascular
stress were achieved. Thus, comparisons between upright and supine exercise hemodynamics are reasonable. Our measurements can also be compared with
those in normal subjects.
One problem with our study is that we did not study
normal controls. Our purpose was not to delineate normal from abnormal, but to evaluate compensatory
mechanisms in patients with severe left ventricular
dysfunction. Extensive values for normal subjects are
available (table 2). A second problem is that the patients were taking various medications. Because our
patients were in well-compensated congestive heart
failure, it would have been unethical to discontinue
their medications. Consequently our results pertain
only to patients receiving adequate medical therapy.
Although the study group was small, the responses of
all of our patients were similar; thus, studies done in a
larger group of patients would probably yield similar
conclusions.
Acknowledgment
We thank Jinx Tracy, Charles Eastham and James Johannsen for
excellent technical assistance and Paula Jennings for helping us to
prepare the manuscript. We also appreciate Dr. Donald Zavala's
thoughtful review of the manuscript.
References
1. Benge W, Litchfield RL, Marcus ML: Exercise capacity in patients
with severe left ventricular dysfunction. Circulation 61: 955, 1980
2. Chidsey CA, Harrison DC, Braunwald E: Augmentation of the
plasma norepinephrine response to exercise in patients with congestive heart failure. N Engl J Med 267: 650, 1962
3. Gorlin R, Cohen LS, Elliott WC, Klein MD, Lane FJ: Effect of
supine exercise on left ventricular volume and oxygen consumption in man. Circulation 32: 361, 1965
4. Ross J, Gault JH, Mason DT, Linhart JW, Braunwald E: Left
ventricular performance during muscular exercise in patients with
and without cardiac dysfunction. Circulation 34: 597, 1966
5. Epstein SE, Beiser GD, Stampfer M, Robinson BF, Braunwald E:
Characterization of the circulatory response to maximal upright
exercise in normal subjects and patients with heart disease. Circulation 35: 1049, 1967
134
CIRCULATION
Downloaded from http://circ.ahajournals.org/ by guest on April 28, 2017
6. Zelis R, Mason DT, Braunwald E: A comparison of the effects of
vasodilator stimuli on peripheral resistance vessels in normal subjects and in patients with congestive heart failure. J Clin Invest 47:
960, 1968
7. Epstein SE, Beiser GD, Stampfer M, Braunwald E: Exercise in
patients with heart disease. Am J Cardiol 23: 572, 1969
8. Patterson JA, Naughton J, Pietras RJ, Gunnar RM: Treadmill
exercise in assessment of the functional capacity of patients with
cardiac disease. Am J Cardiol 30: 757, 1972
9. Franciosa JA: Functional capacity of patients with chronic left
ventricular failure. Am J Med 67: 460, 1979
10. Franciosa JA, Park M, Levine TB: Lack of correlation between
exercise capacity and indexes of resting left ventricular performance in heart failure. Am J Cardiol 47: 33, 1981
11. Sheffield LT: Graded exercise test (GTX) for ischemic heart disease. In AHA Committee on Exercise. A Handbook for Physicians.
Dallas, American Heart Association, 1972, pp 35-38
12. Jones NL: Clinical Exercise Testing. Philadelphia, WB Saunders,
1975
13. Ganz W, Donoso R, Marcus HS, Forrester JS, Swan HJC: A new
technique for measurement of cardiac output by thermodilution in
man. Am J Cardiol 27: 392, 1971
14. Selzer A, Sudrann RB: Reliability of the determination of cardiac
output in man by means of the Fick principle. Circ Res 6: 485,
1958
15. de Champlain J, Farley L, Cousineau D, Van Ameringen MR:
Circulating catecholamine levels in human and experimental hypertension. Circ Res 38: 109, 1976
16. Burow RD, Strauss WH, Singleton R: Analysis of left ventricular
17.
18.
19.
20.
21.
22.
23.
24.
25.
VOL 66, No 1, JULY 1982
function from multiple gated acquisition cardiac blood pool imaging. Circulation 56: 1024, 1977
Feigenbaum H: Echocardiographic examination of the left ventricle. Circulation 51: 1, 1975
Mark AL, Kioschos JM, Abboud FM, Heistad DD, Schmid PG:
Abnormal vascular responses to exercise in patients with aortic
stenosis. J Clin Invest 52: 1138, 1973
Wallenstein S, Zucker CL, Fleiss JL: Special article. Some statistical methods useful in circulation research. Circ Res 47: 1, 1980
Marcus ML, Ehrhardt JC, Verani MS: Reproducibility and sensitivity of the exercise isotope ventriculogram. Clin Res 25: 556A,
1977
Thadani U, Parker JO: Hemodynamics at rest and during supine
and sitting bicycle exercise in normal subjects. Am J Cardiol 41:
52, 1978
Uhley HN, Leeds SE, Sampson JJ, Friedman M: Right duct lymph
flow in experimental heart failure following acute elevation of left
atrial pressure. Circ Res 20: 306, 1967
Eckberg DL, Drabinsky M, Braunwald E: Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med
285: 877, 1971
Zelis R, Flaim SF, Nellis S, Longhurst J, Moskowitz R: Autonomic adjustments to congestive heart failure and their consequences. In Heart Failure, edited by Fishman AP. Washington,
DC, Hemisphere, 1978, pp 237-247
Abboud FM, Thames MD, Mark AL: Role of cardiac afferent
nerves in the regulation of the circulation during coronary occlusion and heart failure. In Disturbances in Neurogenic Control of the
Circulation. Bethesda, Am Physiol Soc, 1981, pp 65, 86
Normal exercise capacity in patients with severe left ventricular dysfunction:
compensatory mechanisms.
R L Litchfield, R E Kerber, J W Benge, A L Mark, J Sopko, R K Bhatnagar and M L Marcus
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Circulation. 1982;66:129-134
doi: 10.1161/01.CIR.66.1.129
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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