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-Adrenergic-mediated improvement in left ventricular
function by exercise training in older men
Section of Applied Physiology, Division of Geriatrics and Gerontology, and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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To test the
hypothesis that the training-induced improvement in the age-related
decline in left ventricular (LV) function is mediated by enhanced
inotropic responses to 
-adrenergic stimulation, 10 sedentary healthy
men, 65 ± 1 yr (mean ± SE) of age, exercised for 9 mo, which
resulted in a 28% increase in aerobic exercise capacity. Training
induced a greater increase in LV systolic shortening, assessed with
two-dimensional echocardiography, in response to isoproterenol with a
steeper slope of the fractional shortening-end-systolic wall stress
(
es) relationship and an
upward shift of the es-systolic diameter relationship without an acute increase in heart rate or
preload. The increase in the early-to-late diastolic flow velocity ratio, normalized for heart rate and preload, in response to
isoproterenol was larger after training. LV systolic reserve and
cardiac output during peak exercise were higher after training.
-Adrenergic blockade with esmolol HCl abolished the adaptive
increases in LV systolic reserve capacity and cardiac output during
peak exercise in the trained state. The results suggest that one of the
underlying mechanisms responsible for the adaptive increase in LV
systolic function in response to exercise training is an enhanced
inotropic sensitivity to catecholamines. Furthermore, the enhanced
inotropic responses are associated with increased diastolic filling.
-adrenergic stimulation
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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MAXIMAL O2 uptake
(
O2 max) decreases at a
rate of 10-15% per decade in sedentary individuals after the age
of 25 yr (2, 7, 22, 23). This reduction is due to
decreases in heart rate, stroke volume, and arteriovenous
O2 content difference during maximal exercise (8, 19, 24). The smaller stroke volume at maximal
exercise in older individuals is a consequence of the age-associated
impairment of myocardial systolic and diastolic function (3, 13, 20,
28), diminished inotropic and chronotropic responses to -adrenergic
stimulation (21, 32, 38), and increased vascular stiffness and aortic
impedance (36, 39). These age-related changes have been attributed to
primary aging and chronic diseases, particularly coronary artery
disease. Physical inactivity probably also contributes to the decline
in O2 max and cardiac
function with advancing age, because endurance exercise training
induces adaptations that can partially reverse the age-related declines
in left ventricular systolic function (4, 33), diastolic filling
dynamics (3, 15), and arterial stiffness in older men (36). The
mechanisms underlying the training-induced improvement in cardiac
performance in older men are unknown. However, in view of the
age-associated decrease in cardiac responses to catecholamines (13, 14)
and because the enhanced systolic performance in response to training
is only detectable during exercise (4, 20), one potential mechanism
could be an enhanced inotropic response to -adrenergic stimulation
in the trained state. Although previous data in young subjects (10, 30)
and experimental animals (17, 37) support this concept, it is not known
whether the improvement in cardiac function in older men is mediated by increased -adrenergic responses in the trained state. In fact, Stratton et al. have recently reported no improvement in left ventricular systolic performance (32) or diastolic filling (34) in
response to isoproterenol after training in older men. One possible
explanation for the lack of increased adaptive responses to
isoproterenol reported by these investigators (32, 34) may be the
confounding effect of increased vagal tone after training, which,
because of its negative inotropic effect (9, 16), could have masked the
enhanced contractile response to the -adrenergic agonist in their
subjects. Therefore, the present study was designed to
1) test the hypothesis that the
training-induced improvement in left ventricular systolic function in
older men is mediated by an increased inotropic response to
-adrenergic stimulation and 2)
determine whether exercise training enhances the
-adrenergic-stimulated increase in diastolic filling in older men.
To minimize the effect of increased vagal tone, we evaluated left
ventricular systolic performance after vagal blockade with atropine.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Subjects
Because the main focus of this study was to evaluate the effects of endurance exercise training on diminished cardiac performance in older men attributed to aging per se, we used rigorous inclusion criteria. These criteria were the absence of the following: 1) cardiopulmonary symptoms; 2) history of hypertension, coronary artery disease, or valvular heart disease; 3) cardiac risk factors, i.e., elevated plasma total and low-density lipoprotein (LDL) cholesterol, hypertension, abnormal glucose tolerance, and smoking; 4) echocardiographic evidence of significant valvular heart disease; 5) exercise-induced myocardial ischemia manifested by either electrocardiogram (ECG) changes (>0.1 mV horizontal or downsloping S-T segment depression) or impaired myocardial perfusion during a thallium-201 exercise test; and 6) angiographic evidence of significant coronary artery disease (1 subject). We selected 11 of 19 men, 60-75 yr of age, who met all of the above criteria. The other eight men exhibited myocardial ischemia on thallium-201 scans and were therefore excluded. Of the remaining 11 eligible men, 1 man had to be excluded because he developed sustained atrial fibrillation during a final exercise test. Therefore, the data for the remaining 10 eligible men, whose ages averaged 65 ± 1 yr (mean ± SE), are reported. The diastolic filling data during exercise for three subjects, assessed with radionuclide angiography, have been reported previously (29). We also recruited 8 men aged 63 ± 1 yr who served as a control group. These men chose not to exercise for personal reasons including frequent travel commitments. They met the same screening criteria as the training group.Measurement of
O2 max
O2 max as previously described (11).
O2 was measured
continuously by open-circuit spirometry with the use of an automated
on-line system described previously (11). The following criteria were used for determining
O2 max:
1) no further increase in
O2 despite an increase in
exercise intensity, 2) a respiratory
exchange ratio of 
1.10, and 3) a
heart rate within 10 beats of the age-predicted maximal heart rate.
Peak O2 was also determined
during upright cycle ergometer exercise during which power output was
increased in 25-W increments every 2 min. This attainment
of peak O2 was established
based on the same criteria used during the treadmill test. Cardiac
output was measured at peak cycle ergometer exercise with the use of
the acetylene rebreathing procedure in six subjects as previously
described (19).
Body Composition
Percent body fat was calculated from body density measured by hydrodensitometry before and after training as previously described (12).Study Design
We evaluated left ventricular (LV) size and function with the use of two-dimensional (2-D) echocardiography 1) at baseline, 2) during infusion of isoproterenol after cardiac muscarinic receptor blockade with atropine, 3) during cycle ergometer exercise, and 4) during cycle exercise with vagal (atropine) and-adrenergic (esmolol infusion) blockade.
Cardiac output was also measured simultaneously using echocardiography
with and without -adrenergic blockade. The studies were performed
before and after training at the same time of day and using the same
intercostal space and body position for the echocardiographic studies.
Echocardiographic and Transmitral Doppler Studies
Two-dimensional and two-dimensional-guided M-mode (Hewlett-Packard model 77020A) echocardiographic images were obtained according to the guidelines recommended by the American Society of Echocardiography (27). The end-diastolic diameter (EDD) and end-systolic diameter (ESD) were measured, and fractional shortening (FS) was calculated using standard guidelines (27). LV end-systolic wall stress (es) was estimated as
described by Grossman et al. (5). An average of six cardiac cycles was
used for the analysis. LV contractile performance was assessed using
the FS-es relationship by
plotting FS as a function of es
and the es-ESD relationship by
plotting es as a function of
ESD for each subject during graded doses of isoproterenol infusion
after vagal blockade (intravenous atropine). Nine of ten subjects had
excellent linear relationships between FS and
es and between
es and ESD. Pulsed Doppler
transmitral diastolic flow velocity profile was used to assess the
effects of training on LV diastolic filling dynamics and the
relationship between LV systolic function and diastolic filling. The
early (E) and late (A) diastolic flow velocities and the ratio of E to
A (E/A) were used as a measure of overall diastolic filling. These
variables were also normalized for heart rate and EDD: (E/A)/[EDD × (R-R)0.5], where R-R
indicates cardiac cycle length.
Cardiovascular Responses to Isoproterenol
The subjects rested in the recumbent position for at least 30 min after insertion of an indwelling intravenous catheter. After baseline echocardiographic and transmitral Doppler images were acquired, each subject received atropine (1.0 mg iv). Atropine was not used in one subject because of symptomatic benign prostatic hypertrophy and concern over urinary retention. Isoproterenol was infused at successive doses of 0.01, 0.02, 0.025, and 0.03 µg · kg
1 · min1
with the use of an infusion pump (model 122; Harvard Apparatus, South
Natick, MA) with ECG and blood pressure monitoring. Each stage of
infusion lasted for ~5 min. Repeat 2-D echocardiographic and
transmitral Doppler images and blood pressure were obtained 2 min after
atropine administration and in the last 2 min of each stage of the
isoproterenol infusion. Transmitral Doppler diastolic flow velocity
profile was available in seven men during isoproterenol infusion.
Cardiovascular Responses During Exercise With and Without
-Adrenergic Blockade
-adrenergic blockade during exercise studies was
that we hypothesized that if the training-induced improvement in LV
systolic performance at peak exercise were mediated by augmented -adrenergic inotropic responses, administration of a -adrenergic blocking agent, i.e., esmolol HCl, should abolish this adaptation. We
were able to obtain satisfactory exercise echocardiographic images from
only six men. The coefficient of variation of FS was 9% at rest and
6% during exercise in our laboratory.
Exercise without -blockade.
The subjects rested in the sitting position for 15 min before the
baseline recordings of 2-D echocardiogram, heart rate, blood pressure,
and O2 were made. The
subjects then performed an incremental upright cycle ergometer test to
exhaustion using a discontinuous exercise protocol (5 min of exercise
followed by 5 min of rest). The incremental work rates were equivalent
to 40, 60, 80, and 100% of previously determined peak
O2. Physiological
measurements including determination of cardiac output were made at
peak exercise.
Exercise during -adrenergic and vagal blockade.
A week later, the subjects performed another cycle ergometer exercise
test. After subjects rested 15 min in the sitting position, physiological measurements were obtained. The subjects then received atropine (1 mg/kg iv), and echocardiographic images and blood pressure
were recorded 2 min later. The subjects were then given a 500 µg/kg
loading dose of esmolol HCl over a 5-min period, followed by infusion
of esmolol HCl at a constant rate of 200 µg · kg1 · min1
that continued throughout the entire experiment. After 2-3 min of
infusion, physiological measurements were obtained at rest. The
subjects then exercised on a cycle ergometer during the infusion of
esmolol HCl using the same absolute work rates and an incremental discontinuous protocol identical to that described in
Exercise without
-blockade. Because of the
-adrenergic blockade, peak O2 was lower in each
subject. Physiological measurements including cardiac output were made
during peak exercise. These protocols were repeated after the
completion of the 9-mo program of endurance exercise training. The
selection of the posttraining work rates were based on
O2 data obtained from the
cycle ergometer test performed after training. The -blockade study
was not performed in the control group.
Exercise Training Program
The exercise training consisted of an initial flexibility and light stretching exercise component (1) that lasted for 2 mo, followed by 9 mo of endurance exercise training as previously described (11). The endurance exercise training program consisted of walking, running, cycle ergometer, and treadmill exercises (11). The subjects were expected to exercise 5 days/wk for 1 h/session. The intensity of exercise was initially adjusted to require 60-70% of the subject'sO2 max and
was increased progressively to 70-80% of
O2 max, supplemented
by additional bouts of interval exercise requiring 90-95% of
O2 max 2 days/wk. O2 max was measured at 3-mo intervals to monitor the effectiveness of the training
and to permit accurate adjustment of the exercise-training intensity to
maintain a constant training stimulus.
Statistics
The differences in physiological variables before and after training were compared with the use of Student's t-test for paired observations when appropriate. In addition, two-way repeated-measures analysis of variance (ANOVA; dose × time) was used to evaluate the responses during the isoproterenol infusion. Significance of differences was evaluated using Newman-Keuls post hoc comparisons. When the data were not normally distributed, nonparametric (ranked order) two-way repeated-measures ANOVA was used. Least squares linear regression was used to determine the slopes of FS-es and es-ESD relationships for each
subject. Data are presented as means ± SE.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Exercise Training Program
The men exercised 4.0 ± 0.2 days/wk for ~9 mo at an intensity averaging 85 ± 2% of their maximal heart rates in the last 3 mo of the training program.O2 max and Heart
Rate
O2 max expressed as
l/min was increased by 22% (2.39 ± 0.11 vs. 2.87 ± 0.11 l/min; P < 0.0001) after
training. When expressed relative to body weight,
O2 max was
increased by 28% (28.8 ± 1.3 vs. 36.8 ± 1.3 ml · kg1 · min1;
P < 0.0001) in response to endurance
exercise training. Maximal heart rate [164 ± 5 vs. 167 ± 3 beats/min; P = not
significant (NS)] and the respiratory exchange ratio (1.15 ± 0.02 vs. 1.17 ± 0.03; P = NS) were
similar before and after training.
Body Composition
Body weight (83.9 ± 3.8 vs. 78.6 ± 3.3 kg; P = 0.002) and percent body fat (27.6 ± 1.4 vs. 22.0 ± 1.9%; P = 0.002) decreased in response to endurance exercise training.Baseline LV Size and Function
Baseline resting LV EDD increased (P = 0.021; Table 1) with no change in the wall thickness-to-radius ratio (0.35 ± 0.015 vs. 0.35 ± 0.017) in response to training, consistent with eccentric LV hypertrophy. LV ESD (Table 1), posterior wall thickness (8.9 ± 0.39 and 9.8 ± 0.36 mm; P = 0.07), the interventricular septum thickness (8.7 ± 0.37 vs. 9.0 ± 0.53 mm; P = 0.6), and FS did not change in response to training. Baseline E/A corrected for heart rate and EDD did not change significantly after training (Fig. 1). Baseline resting heart rate decreased, but blood pressure did not change, in response to training (Table 1). There was no change in any of the baseline variables in the control subjects.
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Cardiovascular Changes After Vagal Blockade
There was a significant increase in heart rate both before and after training in response to atropine (Table 1). The training-induced sinus bradycardia was almost abolished after cardiac muscarinic receptor blockade (P = 0.08; Table 1). There were no changes in blood pressure and FS in response to atropine (Table 1). E/A decreased with atropine (Fig. 1). The effect of training on these variables after cardiac muscarinic receptor blockade was not significant (Table 1).Cardiovascular Responses to -Adrenergic Stimulation
Effect of isoproterenol.
Heart rate, systolic blood pressure, and FS increased significantly
(P < 0.01) in response to
isoproterenol before and after training (Table 1). Diastolic blood
pressure, ESD, and es decreased (P < 0.01) in the trained and
untrained states (Table 1). Isoproterenol had no significant effect on
EDD (Table 1). E/A, in absolute terms or when normalized for heart rate
and EDD, increased significantly in response to isoproterenol (Fig. 1).
Effect of training.
The heart rate response to isoproterenol was slower after than before
training (main effect; P = 0.021).
There were no significant differences in EDD, ESD, FS,
es, and systolic or diastolic
blood pressure between the trained and untrained states during the
infusion of isoproterenol (Table 1). However, the magnitude of increase in FS from the postvagolytic baseline was significantly larger in
response to isoproterenol after than before training
(P = 0.009). Furthermore, the dose
of isoproterenol needed to raise FS by 25% was smaller (0.19 ± 0.003 vs. 0.11 ± 0.001 µg · kg1 · min1;
P = 0.02) in the trained state. The
changes in es or EDD induced by
isoproterenol were not affected by training.
-adrenergic stimulation.
Interaction between isoproterenol and training.
There was a significant interaction between training and isoproterenol
in FS that, at each dose, was significantly higher (P < 0.03) after than before
training (Table 1 and Fig. 2). The FS-es relationship was linear
(n = 9) with correlation coefficients averaging 0.945 ± 0.009 before and 0.926 ± 0.016 after
training. The FS-es
relationship was shifted upward with a markedly steeper slope
(
0.5 ± 0.05 vs. 0.94 ± 0.1;
P = 0.005; Fig.
3) and a greater y-intercept (65 ± 4 before vs. 83 ± 3 after training; P = 0.003; Fig.
4A),
indicating that for a given decrease in
es there was a larger increase
in FS after, compared with before, training (Fig.
4A). The
es-ESD relationship was also
linear with correlation coefficients averaging 0.917 ± 0.035 before
and 0.917 ± 0.025 after training. This relationship was shifted
upward with a less steep slope (1.91 ± 0.16 vs. 3.04 ± 0.31;
P = 0.013; Fig.
4B) and a higher
y-intercept (47 ± 9 before vs. 13 ± 4 after training; P = 0.011; Fig.
4B), indicating that for a given
decrease in ESD there was a smaller reduction in
es after training.
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Cardiovascular Responses During Exercise
Acute effects of -blockade.
Esmolol HCl induced significant decreases in heart rate, systolic blood
pressure, and FS both at rest and during peak exercise (Table
2). EDD and ESD were higher at rest but
were not significantly different during peak exercise during esmolol
HCl infusion (Table 2). Esmolol HCl induced significant reductions in
O2 (from 2.27 ± 0.11 to
2.14 ± 0.13 l/min; P = 0.009) and
cardiac output (from 15.4 ± 0.8 to 13.4 ± 0.4 l/min;
P = 0.008) during peak exercise. Arteriovenous O2 content
difference at peak exercise increased (14.7 ± 0.7 vs. 16.0 ± 0.5 ml/dl; P = 0.035). The changes in
stroke volume during peak exercise were not significant (97 ± 8 vs.
106 ± 6 ml/beat; P = NS).
es did not change (Table 2).
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Adaptations to training.
ADAPTIVE RESPONSES WITHOUT -BLOCKADE.
Training did not affect resting FS (Table 2). However, FS during peak
exercise without -adrenergic blockade was significantly higher after
than before training (Table 2). The effects of training on peak
exercise heart rate, es, ESD,
or EDD were not significant (Table 2). EDD at rest was larger after
than before training (Table 2). Training induced a significant increase
in LV systolic reserve, defined as the difference between peak exercise
and resting FS, with no significant corresponding changes either in
es or EDD (Fig.
5A).
There was a significant decrease in ESD from rest to peak exercise
after, but not before, training (Fig.
6A).
Training resulted in increases in peak exercise cardiac output (15.4 ± 0.8 vs. 18.3 ± 1.0 l/min; P < 0.04), stroke volume (97 ± 8 vs. 118 ± 6 ml/beat;
P = 0.05), and peak
O2 (2.27 ± 0.11 vs. 2.6 ± 0.10 l/min; P < 0.0001).
Arteriovenous O2 content
difference did not change at peak exercise (14.7 ± 0.7 vs. 14.4 ± 0.6 ml/dl) with training.
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-ADRENERGIC BLOCKADE.
There was a smaller increase in FS after than before training with
-adrenergic blockade. However, the magnitude of increase in FS from
rest to exercise (
FS) did not change with training with
-adrenergic blockade (preblockade: 12.8 ± 3%; postblockade: 13.5 ± 3%; P = NS) (Fig.
5B). Training had no significant
effect on es, EDD, ESD,
systolic or diastolic blood pressure, peak heart rate (Table 2 and Fig.
6B), peak
O2 (2.14 ± 0.1 vs. 2.25 ± 0.1 l/min), peak cardiac output (13.4 ± 0.4 vs. 14.8 ± 0.9 l/min), peak stroke volume (106 ± 6 vs. 117 ± 4 ml/beat),
and arteriovenous O2 content
difference (16.0 ± 0.6 vs. 15.4 ± 0.5 ml/dl).
Cardiovascular Responses in Control Group
There were no differences inO2 max in the controls
between the initial and final values (Table
3). The cardiovascular responses to
isoproterenol were also similar initially and 11 mo later. The slopes
of the FS-es (0.50 ± 0.06 vs. 0.53 ± 0.04; P = NS; Fig. 3) and the ESD-es
(2.17 ± 0.4 vs. 2.44 ± 0.3; P = NS) relationships were not different between the initial and final
evaluations.
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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The results of this study suggest that the improvement in LV systolic
function in response to endurance exercise training in older men is, at
least in part, the consequence of enhanced inotropic responses to
catecholamines. The training-induced enhancement of LV systolic
function in response to isoproterenol is evidenced by
1) a steeper slope and a higher
y-intercept of the
FS-es relationship, with
markedly higher values for LV systolic shortening at comparable levels
of estimated es without any
significant changes in EDD, and 2)
an upward shift in the es-ESD
relationship with a higher y-intercept
and a less steep slope, indicating that at a given es, the ESD was smaller in the
trained state. In addition, a greater LV systolic reserve capacity
(FS) and a significant decrease in ESD without changes in
es during peak exercise are
consistent with improvement in contractile function and may account, in
part, for the higher cardiac output and stroke volume during peak
exercise in the trained state. These adaptive increases in LV systolic function, stroke volume, and cardiac output at peak exercise were almost abolished by -adrenergic blockade, providing further evidence to support our hypothesis that the increase in LV systolic performance in older men in response to endurance exercise training is associated with an increased inotropic response to catecholamines. The increase in
LV systolic shortening in response to isoproterenol or during peak
exercise in the trained state could have been due to an increase in
preload (18) and/or to lower aortic impedance and afterload (25, 36). Although we cannot entirely rule out the role of cardiac
loading conditions, the influence of preload appears to be small
because the changes in EDD induced by isoproterenol were similar
between the trained and untrained states.
Previous studies have reported an enhanced response of LV systolic function to catecholamines in the trained state in young subjects (10, 30) and experimental animals (17, 37). In addition, it has been shown in older men and experimental animals that exercise training can partially reverse the age-related deterioration in cardiac function (4, 15, 29, 33, 35). These observations suggest that physical inactivity can play a role in the age-related decline in LV function. A recent study, however, reported no improvement in LV systolic performance in response to isoproterenol after training (32). The reasons for the disparity between our findings and those of others are not clear but may be related, in part, to differences in the study design. Endurance exercise training increases vagal tone, which, by enhancing its negative inotropic effect particularly in response to high levels of catecholamines (9, 16), can counteract the adaptive increase in cardiac function. Therefore, it is possible that even partial cardiac muscarinic receptor blockade in this study may account for the differences between our findings and those of others (32, 34).
Our findings are in keeping with previous reports (10, 30) that, in
contrast to an enhanced inotropic response, the chronotropic response
to catecholamines may not change significantly as a result of exercise
training. The mechanisms underlying the absence of an increase in heart
rate responses are not clear but may be due in part to selective
reduction of -adrenoceptors in the right atrium associated with
diminished chronotropic responses to isoproterenol, as shown in pigs in
response to training (6). Because of the slower heart rate response,
the enhanced systolic function in the trained state is unlikely to be
mediated by the force-frequency relationship (26).
The larger isoproterenol-stimulated increase in the early-to-late
diastolic flow velocity ratio (E/A), normalized for heart rate and
preload, suggests a -adrenergic-mediated increase in LV diastolic
filling in the trained state. This adaptation may provide a mechanism
for the enhanced LV filling during exercise in older trained men (15,
29). Levy et al. (15) have shown an increase in LV diastolic filling
during exercise after training in older men that, unlike the findings
in the present study, was not associated with augmented responses of
diastolic filling to isoproterenol (34). The reasons for these
disparate findings are not clear but may be related in part to the use
of atropine in our study.
One of the limitations of this study is a relatively small sample size. However, because our main objective was to determine the mechanisms underlying the effects of exercise training on the decline in cardiac function attributable to aging, we used rigorous criteria to exclude coronary artery disease, which is common in older men. Even with a relatively small sample size, we found statistically significant differences in several physiological variables. Furthermore, the control group, which was similar to the exercise group, did not exhibit any significant change in cardiac responses to isoproterenol. Another limitation is the inherent problems with echocardiography, particularly during exercise. We also recognize that vagal blockade was incomplete in our study because of our concern regarding the adverse side effects of atropine in older men. Therefore, because of these limitations, our findings should be interpreted with caution.
In conclusion, the results of the present study provide evidence that an adaptive increase in cardiac responses to catecholamines is one of the mechanisms responsible for the improvement in not only LV systolic performance but also diastolic filling in response to endurance exercise training in older men.
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ACKNOWLEDGEMENTS |
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This work was supported by National Institutes of Health Grants AG-05562 and MO1-RR-00036 to the General Clinical Research Center. M. J. Turner was supported by Institutional National Research Service Award AG-00078.
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FOOTNOTES |
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Present address of M. J. Turner: Campus Box 16, Dept. of Health and Physical Education, Wichita State Univ., Wichita, KS 67260.
Address for reprint requests: R. J. Spina, Div. of Geriatrics and Gerontology, Washington Univ. School of Medicine, 4566 Scott Ave., Box 8113, St. Louis, MO 63110.
Received 25 April 1997; accepted in final form 8 October 1997.
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REFERENCES |
|---|
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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1.
Brown, M.,
and
J. O. Holloszy.
Effects of a low intensity exercise program on selected physical performance characteristics of 60- to 71-year-olds.
Aging (Milano)
3:
129-139,
1991[Medline].
2.
Buskirk, E. R.,
and
J. L. Hodgson.
Age and aerobic power: the rate of change in men and women.
Federation Proc.
46:
1824-1829,
1987[Medline].
3.
Douglas, P. S.,
and
M. O'Toole.
Aging and physical activity determine cardiac structure and function in the older athlete.
J. Appl. Physiol.
72:
1969-1973,
1992
4.
Ehsani, A. A.,
T. Ogawa,
T. R. Miller,
R. J. Spina,
and
S. M. Jilka.
Exercise training improves left ventricular systolic function in older men.
Circulation
83:
96-103,
1991
5.
Grossman, W.,
D. Jones,
and
L. P. McLaurin.
Wall stress and patterns of hypertrophy in the human left ventricle.
J. Clin. Invest.
56:
56-64,
1975.
6.
Hammond, H. K.,
F. C. White,
L. L. Brunton,
and
J. C. Longhurst.
Association of decreased myocardial -receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise.
Circ. Res.
60:
720-726,
1987
7.
Heath, G. W.,
J. M. Hagberg,
A. A. Ehsani,
and
J. O. Holloszy.
A physiological comparison of young and older athletes.
J. Appl. Physiol.
51:
634-640,
1981
8.
Higginbotham, M. B.,
K. G. Morris,
R. S. Williams,
E. R. Coleman,
and
F. R. Cobb.
Physiologic basis for the age-related decline in aerobic work capacity.
Am. J. Cardiol.
57:
1374-1379,
1986[Medline].
9.
Hollenberg, M.,
S. Carriere,
and
A. C. Barger.
Biphasic action of acetylcholine on ventricular myocardium.
Circ. Res.
16:
527-536,
1965
10.
Hopkins, M. G.,
R. J. Spina,
and
A. A. Ehsani.
Enhanced -adrenergic-mediated cardiovascular responses in endurance athletes.
J. Appl. Physiol.
80:
516-521,
1996
11.
Kohrt, W. M.,
M. T. Malley,
A. R. Coggan,
R. J. Spina,
T. Ogawa,
A. A. Ehsani,
R. E. Bourey,
W. H. Martin III,
and
J. O. Holloszy.
Effects of gender, age, and fitness level on responses of O2 max to training in 60-71 yr olds.
J. Appl. Physiol.
71:
2004-2011,
1991
12.
Kohrt, W. M.,
M. T. Malley,
G. P. Dalsky,
and
J. O. Holloszy.
Body composition of healthy sedentary and trained young and older men and women.
Med. Sci. Sports Exerc.
24:
832-837,
1992[Medline].
13.
Lakatta, E. G.
Cardiovascular regulatory mechanisms in advanced age.
Physiol. Rev.
73:
413-467,
1993
14.
Lakatta, E. G.,
G. Gerstenblith,
C. S. Angell,
N. W. Shock,
and
M. L. Weisfeldt.
Prolonged contraction duration in aged myocardium.
J. Clin. Invest.
55:
61-68,
1975.
15.
Levy, W. C.,
M. D. Cerqueira,
I. B. Abrass,
R. S. Schwartz,
and
J. R. Stratton.
Endurance exercise training augments diastolic filling at rest and during exercise in healthy young and older men.
Circulation
88:
116-126,
1993
16.
Levy, N. W.,
M. Ng,
P. Martin,
and
H. Zieske.
Sympathetic and parasympathetic interactions upon the left ventricle of the dog.
Circ. Res.
19:
5-10,
1966
17.
Molé, P. A.
Increased contractile potential of papillary muscles from exercise-trained rat hearts.
Am. J. Physiol.
234 (Heart Circ. Physiol. 3):
H421-H425,
1978
18.
Nixon, J. V.,
P. D. Murray,
P. D. Leonard,
J. H. Mitchell,
and
C. G. Blomqvist.
Effect of large variation in preload on left ventricular performance characteristics in normal subjects.
Circulation
65:
698-703,
1982
19.
Ogawa, T.,
R. J. Spina,
W. H. Martin III,
W. M. Kohrt,
K. B. Schechtman,
J. O. Holloszy,
and
A. A. Ehsani.
Effects of aging, sex, and physical training on cardiovascular responses to exercise.
Circulation
86:
494-503,
1992
20.
Port, S.,
F. R. Cobb,
E. R. Coleman,
and
R. H. Jones.
Effect of age on the response of the left ventricular ejection fraction to exercise.
N. Engl. J. Med.
303:
1133-1137,
1980[Abstract].
21.
Raven, P. B.,
and
J. H. Mitchell.
The effect of aging on the cardiovascular response to dynamic and isometric exercise.
In: The Aging Heart, edited by M. L. Weisfeldt. New York: Raven, 1980, vol. 12, p. 269-296.
22.
Robinson, S.
Experimental studies of physical fitness in relation to age.
Arbeitsphysiologie
10:
251-323,
1938.
23.
Robinson, S.,
D. B. Dill,
and
J. A. Wagner.
Physiological aging of champion runners.
J. Appl. Physiol.
41:
46-51,
1976
24.
Rogers, M. A.,
J. M. Hagberg,
W. H. Martin III,
A. A. Ehsani,
and
J. O. Holloszy.
Decline in O2 max with aging in master athletes.
J. Appl. Physiol.
68:
2195-2199,
1990
25.
Ross, J., Jr.
Afterload mismatch and preload reserve: a conceptual framework for the analysis of ventricular function.
Prog. Cardiovasc. Dis.
18:
255-264,
1976[Medline].
26.
Ross, J., Jr.,
T. Miura,
M. Kambayashi,
G. P. Eising,
and
K. H. Ryu.
Adrenergic control of the force-frequency relation.
Circulation
92:
2327-2332,
1995
27.
Sahn, D. J.,
A. DeMaria,
J. Kisslo,
and
A. Weyman.
Recommendations regarding quantitation M-mode echocardiography: results of a survey of echocardiographic measurements.
Circulation
58:
1072-1083,
1978
28.
Schulman, S. P.,
E. G. Lakatta,
J. L. Fleg,
L. Lakatta,
L. C. Becker,
and
G. Gerstenblith.
Age-related decline in left ventricular filling at rest and during exercise.
Am. J. Physiol.
263 (Heart Circ. Physiol. 32):
H1932-H1938,
1992
29.
Spina, R. J.,
T. R. Miller,
W. H. Bogenhagen,
K. B. Schechtman,
and
A. A. Ehsani.
Gender-related differences in left ventricular filling dynamics in older subjects after endurance exercise training.
J. Gerontol. A Biol. Sci. Med. Sci.
51:
232-237,
1996.
30.
Spina, R. J.,
T. Ogawa,
A. R. Coggan,
J. O. Holloszy,
and
A. A. Ehsani.
Exercise training improves left ventricular contractile response to -adrenergic agonist.
J. Appl. Physiol.
72:
307-311,
1992
31.
Spurgeon, H. A.,
M. F. Steinbach,
and
E. G. Lakatta.
Chronic exercise prevents characteristic age-related changes in rat cardiac contraction.
Am. J. Physiol.
244 (Heart Circ. Physiol. 13):
H513-H518,
1983.
32.
Stratton, J. R.,
M. D. Cerqueira,
R. S. Schwartz,
W. C. Levy,
R. C. Veith,
S. E. Kahn,
and
I. B. Abrass.
Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.
Circulation
86:
504-512,
1992
33.
Stratton, J. R.,
W. C. Levy,
M. D. Cerqueira,
R. S. Schwartz,
and
I. B. Abrass.
Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men.
Circulation
89:
1648-1655,
1994
34.
Stratton, J. R.,
W. C. Levy,
R. S. Schwartz,
I. B. Abrass,
and
M. D. Cerqueira.
-Adrenergic effects on left ventricular filling: influence of aging and exercise training.
J. Appl. Physiol.
77:
2522-2529,
1994
35.
Tate, C. A.,
G. E. Taffet,
E. K. Hudson,
S. L. Blaylock,
R. P. McBride,
and
L. H. Michael.
Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained rats.
Am. J. Physiol.
246 (Heart Circ. Physiol. 15):
H431-H435,
1984.
36.
Vaitkevicius, P. V.,
J. L. Fleg,
J. H. Engle,
F. C. O'Connor,
J. G. Wright,
F. C. P. Yin,
and
E. G. Lakatta.
Effects of age and aerobic capacity on arterial stiffness in healthy adults.
Circulation
88:
1456-1462,
1993
37.
Wyatt, H. L.,
L. Chuck,
B. Rabinowitz,
J. V. Tyberg,
and
W. W. Parmley.
Enhanced cardiac response to catecholamines in physically trained cats.
Am. J. Physiol.
234 (Heart Circ. Physiol. 3):
H608-H613,
1978.
38.
Yin, F. C. P.,
H. A. Spurgeon,
H. L. Green,
E. G. Lakatta,
and
M. L. Weisfeldt.
Age-associated decrease in heart rate response to isoproterenol in dogs.
Mech. Ageing Dev.
10:
17-25,
1979[Medline].
39.
Yin, F. C. P.,
M. L. Weisfeldt,
and
W. R. Milnor.
Role of aortic impedance in the decreased cardiovascular response to exercise with aging in dogs.
J. Clin. Invest.
68:
28-38,
1981.
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