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Circulation. 1996;94:323-330

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(Circulation. 1996;94:323-330.)
© 1996 American Heart Association, Inc.

Articles

Skeletal Muscle and Cardiovascular Adaptations to Exercise Conditioning in Older Coronary Patients

Philip A. Ades, MD; Mary L. Waldmann, BSN; William L. Meyer, PhD; Kenneth A. Brown, MD; Eric T. Poehlman, PhD; William W. Pendlebury, MD; Kevin O. Leslie, MD; Peter R. Gray, MD; Richard R. Lew, BS; Martin M. LeWinter, MD

the Divisions of Cardiology, Biochemistry, and Pathology, University of Vermont College of Medicine, Burlington.


*    Abstract
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 *Abstract
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 down arrowResults
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Background Older coronary patients suffer from a low functional capacity and high rates of disability. Supervised exercise programs improve aerobic capacity in middle-aged coronary patients by improving both cardiac output and peripheral extraction of oxygen. Physiological adaptations to aerobic conditioning, however, have not been well studied in older coronary patients.

Methods and Results The effect of a 3-month and a 1-year program of intense aerobic exercise was studied in 60 older coronary patients (mean age, 68±5 years) beginning 8±5 weeks after myocardial infarction or coronary bypass surgery. Outcome measures included peak aerobic capacity, cardiac output, arteriovenous oxygen difference, hyperemic calf blood flow, and skeletal muscle fiber morphometry, oxidative enzyme activity, and capillarity. Training results were compared with a sedentary, age- and diagnosis-matched control group (n=10). Peak aerobic capacity increased in the intervention group at 3 months and at 1 year by 16% and 20%, respectively (both P<.01). Peak exercise cardiac output, hyperemic calf blood flow, and vascular conductance were unaffected by the conditioning protocol. At 3 and 12 months, arteriovenous oxygen difference at peak exercise was increased in the exercise group but not in control subjects. Histochemical analysis of skeletal muscle documented a 34% increase in capillary density and a 23% increase in succinate dehydrogenase activity after 3 months of conditioning (both P<.02). At 12 months, individual fiber area increased by 29% compared with baseline (P<.01).

Conclusions Older coronary patients successfully improve peak aerobic capacity after 3 and 12 months of supervised aerobic conditioning compared with control subjects. The mechanism of the increase in peak aerobic capacity is associated almost exclusively with peripheral skeletal muscle adaptations, with no discernible improvements in cardiac output or calf blood flow.


Key Words: exercise • heart diseases • ischemia • aging


*    Introduction
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 up arrowAbstract
 *Introduction
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The mean age of patients who suffer a myocardial infarction or undergo coronary bypass surgery in the United States is now over 65 years.1 2 3 Compared with younger coronary patients, older patients have a diminished exercise capacity4 and higher rates of disability and mobility limitations.5 6 In the Framingham Disability Study,5 the presence of coronary heart disease was associated with significant mobility or physical work limitations in 79% of women and 49% of men older than 70 years of age. The established clinical benefits of supervised aerobic conditioning that have been determined in middle-aged coronary patients include an increased maximal work capacity7 and an increased work intensity at the anginal threshold for patients with exercise-induced ischemia.8 Meta-analyses of studies performed in primarily male, middle-aged, post–myocardial infarction patients randomized to exercise programs suggest a decreased overall and cardiovascular mortality.9 10

Several training studies11 12 13 14 documented the feasibility of exercise conditioning in older coronary patients. Although the exercise-training data of the present investigation were published recently,15 this presentation focuses on the physiological mechanisms of conditioning, which were not described previously. Physiological responses to training in middle-aged coronary populations include both peripheral adaptations, which result in a widened arteriovenous oxygen difference at maximal exercise,16 17 and cardiac adaptations, which include increases in cardiac dimensions, stroke work, cardiac output, and afterload-corrected indexes of left ventricular function.18 19 20 21 Similarly, in healthy subjects of all ages, including the elderly, intensive, aerobic training programs improve both cardiac function and the peripheral utilization and extraction of oxygen during exercise.17 22 23 24 In older coronary patients, coronary and peripheral vascular disease are superimposed on "normal" aging-related increases in left ventricular and arterial wall thickness and stiffness.25 26 27 This may result in a limitation in cardiovascular adaptations to aerobic conditioning. Accordingly, in the present study, we tested the hypothesis that conditioning-induced adaptations in older coronary patients are primarily noncardiovascular in nature. If true, this may have implications regarding optimal training techniques in this group of patients.


*    Methods
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 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
 down arrowDiscussion
 down arrowReferences
 
The conditioning effects of a 12-week (n=60) and a 1-year (n=22) aerobic training program were determined in a population of older coronary patients with a mean age of 68±5 years (range, 62 to 82 years); 41 were men (aged 68±5 years) and 19 were women (aged 69±6 years). Results were compared with members of an age-matched, sedentary control group (n=10) who were also tested at baseline, 3 months, and 1 year. Subjects in the sedentary control group were not randomized but rather had no geographic access to an organized cardiac rehabilitation program and did not participate in a home exercise program. The sedentary control subjects were selected from a larger group of 23 "usual care" control subjects, of whom 13 actually exercised regularly on their own at least 90 minutes per week and thus were not considered sedentary. This group is described further in a prior publication.15 The intervention and sedentary control patients were similar in age (68±5 versus 68±4 years, respectively), sex (32% women versus 30% women), time since cardiac event (8±5 versus 9±5 weeks), body weight (76±13 versus 75±12 kg), peak aerobic capacity (19.4±6 versus 18.5±3 mL·kg-1·min-1) and resting left ventricular ejection fraction measured by radionuclide ventriculography (51±11% versus 50±10%). All patients had experienced a coronary event within the previous 12 weeks; myocardial infarction had occurred in 32 of the intervention patients and 5 of the control subjects and coronary bypass surgery had been performed in 28 of the intervention patients and 5 of the control subjects. Before baseline testing, all candidates underwent a familiarization, symptom-limited treadmill test with ECG monitoring and expired gas collection.28 All subjects also underwent a resting radionuclide ventriculogram for determination of left ventricular ejection fraction. Subjects were excluded from the study if resting left ventricular ejection fraction was <30% or if they had severe exertional ischemia (>3 mm ST-segment depression), severe exertional arrhythmias, or a noncardiopulmonary limitation to exercise (eg, arthritis, claudication, or hemiparesis). All candidates gave their informed consent as approved by the University of Vermont Committee on Human Research.

Exercise Training Protocol
The exercise training protocol consisted of a 12-week, 3 hour-per-week program of telemetry-monitored treadmill, stationary bicycle, and rowing ergometer exercise with intensity levels guided by exercise heart rate, which initially was maintained at 75% to 85% of maximal exercise heart rate. Because older coronary patients frequently do not reach a true physiologically maximal effort during post–coronary event exercise testing,4 after 2 weeks of conditioning, training intensity was increased as tolerated to 85% to 90% of maximal heart rate attained during the preconditioning stress test. Treadmill exercise lasted 25 minutes per session, bicycle exercise 15 minutes, and rowing ergometer 10 minutes per session, preceded and followed by warm-up, stretching, and cooldown. Modifications of the program for particularly unfit patients were minor and included beginning the exercise program with intermittent bouts of exercise to the same total duration as more fit patients. Mean attendance for scheduled exercise sessions was 91%. The intervention group also was encouraged to walk at home for 20 to 30 minutes 1 additional day per week within their prescribed heart rate range.

A subset of 22 of the 55 patients who completed the conditioning program agreed to continue their exercise training for an additional 9 months and were then retested. The age, sex, and peak O2 of these patients did not differ from the patients who trained for only 3 months. Study evaluations, performed at baseline, 3 months, and 12 months, used the methodologies discussed below.

Maximal Exercise Capacity
Maximal exercise capacity was determined by repeating the symptom-limited treadmill test with use of a single metabolic equivalent Balke protocol,29 with subjects breathing into a Hans-Rudolph mouthpiece and a Sensormedics Horizon metabolic cart used for analysis of expired air. Baseline testing was performed 8±5 weeks after the coronary event.

At baseline, 25 of 60 intervention patients and 3 of 10 control patients were taking ß-adrenergic blocking medications (P=NS). Although ß-blockers have been demonstrated to attenuate response to exercise conditioning in normal subjects and hypertensives, they do not appear to alter conditioning in coronary patients.30 31 32 Medication alterations during the training program were minimal.

Radionuclide Ventriculography
Both the intervention group and the control group underwent radionuclide ventriculography at rest and at peak cycle exercise by use of a standard, planar, Anger gamma camera equipped with a parallel-hole collimator and a three-eighths–inch crystal positioned over the heart in the left anterior oblique projection that best separated the right and left ventricles. Autologous red blood cells were labeled with 25 mCi of 99mTc with a modified in vitro technique.33 34 Gated images were collected in a 64x64 matrix at 16 frames per cardiac cycle. Resting radionuclide ventriculograms were collected to a count density of 200 000 counts in the left ventricular region of interest. Subsequently, image acquisition was performed during the final 3 minutes of each stage of exercise. End-diastolic and end-systolic left ventricular regions of interest were drawn manually. Ejection fraction was calculated as background-corrected counts by use of the formula

where EF is ejection fraction. In our laboratory, the standard deviation for repetitive measurements of left ventricular ejection fraction with this method is 1.6% (ejection fraction units).34 Absolute left ventricular volumes for each collection were determined by use of a previously validated counts-based technique with attenuation correction.35 36 37 Attenuation correction was determined for each patient by obtainment of a left anterior oblique static image with a 57Co marker in the center of the cardiac blood pool and a second anterior image exactly 40° from the modified left anterior oblique scan with the 57Co marker in the same position.36 37 38 An attenuation coefficient was determined from the calculated depth of the center of the left ventricle assuming an attenuation coefficient of water (0.15 cm2/g). Cycle ergometry was performed on an electronically braked ergometer angled at 45° (Engineering Dynamics Corp) with work rates increased by 25 W every 4 minutes until exhaustion or occurrence of limiting cardiopulmonary symptoms such as angina, dyspnea, or dizziness.

Arteriovenous Oxygen Difference
Arteriovenous oxygen difference (AVO2 Diff) at peak exercise was estimated in both groups by the modified Fick equation: AVO2 Diff=oxygen consumption/cardiac output.

Skeletal Muscle Blood Flow
The exercise-intervention group underwent calf blood-flow determinations by the venous occlusion technique with a strain gauge capacitance plethysmograph (UFI). Measurements were made at rest and after ischemic exercise. The ischemic exercise consisted of exhaustive toe-raising exercise over a 1- to 2-minute period with a thigh cuff inflated to 300 mm Hg until the claudication-like pain became intolerable. Postexercise measures were taken immediately after exercise during the sustained hyperemia that followed release of the thigh cuff and arterial inflow.38 39 Resting and hyperemic blood flows were expressed as mL·min-1·100 mL-1 tissue. Resting and maximal calf conductances were calculated as blood flow divided by mean blood pressure, and hyperemic flow reserve was determined as hyperemic minus resting calf blood flow. The control group did not have calf blood-flow measures or skeletal muscle biopsies (see below).

Body Composition
Body composition was determined in a subset of 10 intervention patients before and after 3 months of conditioning by the skin-fold technique with calculation of percent body fat, fat weight, and fat-free weight.40 Skin folds were taken from the triceps, subscapular, biceps, and abdominal sites by the same investigator (E.T.P.). The reliability coefficient and the coefficient of variation for repeated measurements of skin folds in our laboratory as determined in 18 older women (aged 55 to 75 years) are 0.98% and 3.4%, respectively.41

Skeletal Muscle Morphometry
Skeletal muscle biopsy samples were obtained at rest from the vastus lateralis muscle with a Bergstrom needle at baseline and after 3 and 12 months of conditioning by use of a percutaneous technique.42 Mean sample size was 64 mg wet wt. A sample for histochemical and morphometric analysis was flash-frozen in liquid nitrogen (-70°C), cryosectioned at -20°C, and mounted on glass microscope slides with a cross-sectional orientation. Muscle fiber–type composition was determined by staining for myofibrillar ATPase activity at pH 9.4, 4.7, and 4.3. Capillary endothelium was visualized microscopically by use of an antiserum against coagulation factor VIII–related antigen (polyclonal FVIII, Dako Corp) and a streptavidin visualization method and measured by use of a Bioquant image-analysis system (R&M Biometrics). Semiquantitative localization was achieved by use of the gray-scale analysis mode of this instrument, in which immunocytochemical reaction product was visualized and measured as a standardized, two-dimensional area of capillarity43 (FigureDown). Slides were coded and analyzed without knowledge of patient identity or training status. Derived morphometric measures included individual fiber area, fiber-type composition, and capillary density.



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  		Figure 1. Quantification of capillary density. Capillaries are visualized with factor VIII–related antigen. Capillary density is estimated by gray-scale thresholding of capillaries (dark areas; some denoted by arrows).

Skeletal Muscle Oxidative Enzyme Capacity
Skeletal muscle oxidative capacity was assessed by measurement of succinate dehydrogenase (SDH) activity in the biopsy sample, before and after conditioning, by use of an adaptation of the method of Lee and Lardy.44 45 Glycogen stores in the muscle sample were measured by a coupled enzyme assay applied to sulfuric acid hydrolysates of the muscle sample.46 Protein content was measured by use of an adaptation of the dye-binding method of Sedmak and Grossberg47 with bovine serum albumin used as a standard. Preconditioning and postconditioning biopsies were performed at the same time of day; however, patients were not on a controlled diet.

Statistical Analysis
A two-way repeated ANOVA (with group and time as the factors) was used to analyze baseline, 3-month, and 12-month data. Linear regression analysis was used to examine relations between variables. All data are reported as mean±SD. A value of P<.05 was considered to indicate a statistically significant difference.


*    Results
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 *Results
down arrowDiscussion
 down arrowReferences
 
The 3-month aerobic conditioning program was completed by 55 of the original 60 entrants. Nine of the 10 sedentary control subjects appeared for 3-month and 12-month testing. Two intervention subjects dropped out for nonexercise-related cardiac problems (congestive heart failure and recurrent supraventricular tachycardia) and 3 dropped out for noncardiac medical problems (hip and back arthritis and poststernotomy nonunion). There were no further dropouts among the 22 patients who agreed to conditioning for a full 12 months. The 70 study subjects were quite unfit at baseline, as is characteristic of older coronary patients, with a peak aerobic capacity (peak O2) of 19.1±6 mL·kg-1·min-1 at baseline.

After 3 months of conditioning, peak O2 increased by 16% (from 19.4±6 to 22.4±7 mL·kg-1·min-1; P<.001), and at 12 months (n=22) by 20% (from 19.1±7 to 22.9±8 mL·kg-1·min-1; P<.002). In the sedentary control group, peak O2 was unaltered after 3 and 12 months (from 18.5±3 mL·kg-1·min-1 at baseline to 18.7±3 at 3 months and 18.8±5 at 12 months; P=NS). Peak respiratory equivalent ratio was similar between groups at baseline (1.09±0.11 versus 1.06±0.10 in control subjects; P=NS) and did not increase with training in either group (Table 1Down). This suggests a similar peak exercise effort between groups at baseline and on retesting. In the exercise group, duration of treadmill exercise, ie, maximal work capacity, increased at 3 months by 47% (from 8.8±3 to 13.0±4 minutes; P<.001) and at 12 months by 47% (from 9.1±4 to 13.3±4 minutes; P<.002). In the control group, duration of treadmill exercise did not change from baseline to 3 and 12 months (from 8.2±2 to 7.4±1 at 3 months to 8.3±2 minutes at 12 months; P=NS). Men and women improved peak O2 similarly with conditioning at 3 months, with an increase of 17% in men and 16% in women (P=NS). Baseline diagnosis (myocardial infarction versus coronary bypass surgery) did not alter training magnitude, nor did use of ß-adrenergic blocking medications (both P=NS). Maximal heart rate during treadmill exercise was unaffected by conditioning (123±20 versus 124±25 bpm at 3 months and 127±21 bpm in the 22 patients who exercised for 12 months; all P=NS). Body weight was unaltered by the conditioning program (75.6±12 versus 74.8±13 kg; P=NS). However, estimated fat-free mass increased from 52.4±8 to 53.6±8 kg (P<.05), and fat mass decreased from 24.5±7 to 22.5±9 kg (P<.05) in a subset of 10 intervention patients over 3 months.


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  		Table 1. Peak Exercise Expired-Gas Analysis

During cycle ergometry testing, maximal workload increased in the exercise group from 83±32 to 93±28 W (P<.001) at 3 months of conditioning, whereas maximal heart rate did not change (119±21 to 121±23 bpm; P=NS). In the control group, maximal workload on the cycle ergometer did not change at 3 months (70±27 to 77±29 W; P=NS); peak heart rate was also unaltered (118±22 to 119±21 bpm). In the 22 patients who exercised for 12 months, maximal workload (97±28 W) and maximal heart rate (115±20 bpm) were not further altered.

Resting and peak exercise left ventricular ejection fraction were unchanged after conditioning at both 3 and 12 months both in intervention patients and in control subjects (Table 2Down). Rest and peak exercise stroke volume and cardiac output were also unaltered by the conditioning program at 3 and 12 months (Table 2Down). Peak AVO2 Diff increased in the intervention group at 3 months (11.6±8 to 14.4±9 mL/L; P=.005) and at 12 months (11.6±4 to 14.6±6 mL/L; P=.06). In the control group, no changes in peak AVO2 Diff were noted at 3 or 12 months (10.5±4 to 10.8±6 mL/L at 3 months and 10.2±6 mL/L at 12 months; all P=NS).


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  		Table 2. Cardiac Response to Exercise Conditioning

In the intervention group, both peak exercise end-diastolic volume and end-systolic volume tended to decrease after 3 months of conditioning (P=.07 and P=.06, respectively), whereas no trends were observed in the control subjects (Table 2Up). Resting end-diastolic and end-systolic volumes were unaltered after 3 months of conditioning (197±79 to 186±73 mL and 103±58 to 92±51 mL, respectively; both P=NS). When we divided peak exercise left ventricular ejection fraction by peak end-diastolic volume, this index of left ventricular performance was increased after 3 months of conditioning in the exercise group (P=.03; Table 3Down). When peak exercise ejection fraction was divided by peak end-systolic volume and peak systolic blood pressure, no change in these indexes was noted. Similarly, peak exercise systolic blood pressure divided by peak end-systolic volume was unaltered after 3 months of conditioning (Table 3Down). Thus, although the increase in peak O2 (cardiac output times A VO2 Diff) in both men and women was primarily due to an increase in arteriovenous extraction of O2, we did find some evidence of an improvement in left ventricular performance when peak exercise ejection fraction was divided by end-diastolic volume, an estimate of left ventricular preload. In the control group, there were no changes in rest and peak ejection fractions, end-diastolic volume, or cardiac output at 3 and 12 months. Rest ejection fraction at baseline, 3 months, and 12 months was 50±10%, 51+9%, and 50±9%, respectively, and peak ejection fraction was 55±13%, 52±16%, and 53±7%, respectively (all P=NS). At the same time points, rest end-diastolic volume was 205±85, 223±121, and 220±96 mL, and peak end-diastolic volume was 210±99, 217±114, and 216±89 mL (all P=NS). Rest cardiac output was 6.5±2.8, 7.4±1.7, and 7.1±1.7 L/min at baseline, 3 months, and 12 months, respectively, and peak cardiac output was 13.2±5.2, 13.0±4.7, and 13.4±5.1 L/min, respectively (all P=NS). Load-corrected indexes of left ventricular performance were unaltered at 3 and 12 months in control subjects.


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  		Table 3. Load-Adjusted Indexes of Cardiac Performance

Resting calf blood flow, hyperemic calf blood flow, rest and hyperemic vascular conductance (flow divided by mean blood pressure), and flow reserve (hyperemic minus resting blood flow) were all unaffected by the conditioning program after 3 and 12 months (Table 4Down). There was no significant correlation between change in peak blood flow or peak conductance and change in peak O2 after 3 months of training (r=.11, P=NS for both).


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  		Table 4. Calf Blood Flow and Conductance

Muscle fiber–type composition was determined in the muscle biopsy specimen before and after 3 and 12 months of conditioning (Table 5Down). At baseline, 47% of stained biopsy fibers were type 1 and 53% were type 2. After 3 and 12 months of conditioning, this ratio was unchanged. Mean individual fiber area was not significantly altered by the conditioning program at 3 months. However, in the patients who exercised for 12 months, individual fiber area increased by 29% (P<.01) compared with baseline. After 3 months of conditioning, capillary density of the vastus lateralis muscle sample was increased by 34% (P<.05) (FigureUp).


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  		Table 5. Skeletal Muscle Morphometry

Muscle biopsy–specimen SDH activity, glycogen content, and protein content are shown in Table 6Down. SDH activity increased over the 3-month conditioning period by 23% from 4.35±1.63 to 5.36±2.90 enzyme units/mg wet wt (P=.018). There was no significant correlation between change in SDH activity with training and increase in peak O2 (r=.12, P=NS). Glycogen stores and protein content in the resting muscle samples were unaltered by conditioning.


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  		Table 6. Skeletal Muscle Biochemistry


*    Discussion
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 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
The endurance exercise–training program induced substantial improvements in peak exercise capacity and work capacity in the study population at 3 and 12 months of training compared with control patients. The hypothesis that older patients condition predominantly by noncardiac adaptations is supported by the fact that the increases in peak aerobic exercise capacity were mediated primarily by an increase in peak exercise AVO2 Diff with no measurable increase in peak exercise cardiac output. The increase in peak AVO2 Diff was associated with adaptations of skeletal muscle fiber size, capillarity, and SDH activity with only subtle alterations in cardiac performance and no discernible alterations of peripheral arterial blood flow. The skeletal muscle adaptations consisted of an increased oxidative enzyme activity and an increased capillary density after 3 months of conditioning and an increased muscle fiber cross-sectional area after 12 months of conditioning. However, although directional changes of fiber size, capillarity, and SDH activity and changes in peak O2 and AVO2 Diff were in a consistent direction, the correlation coefficients were low.

Although there were no measurable increases in peak exercise cardiac output after conditioning, there was a tendency to a higher peak exercise ejection fraction (P=.07), and peak exercise ejection fraction divided by peak exercise end-diastolic volume was increased after 3 months of conditioning (P<.05), which suggests an improvement in peak left ventricular performance. The clinical characteristics of the study population were typical of post–coronary event patients in this age group in that there was a markedly diminished functional capacity and a high rate of comorbidities.48

These conditioning mechanisms differ somewhat from those reported in younger coronary patients and in healthy subjects. Numerous investigators have documented peripheral adaptations to aerobic conditioning in middle-aged coronary patients and healthy subjects. These include increases in AVO2 Diff, skeletal muscle oxidative enzyme activity, and muscle fiber capillarity.16 17 49 50 In addition, increases in peak exercise end-diastolic volume, stroke volume, and cardiac output have been documented after 12 months of conditioning.18 19 In the present study population, end-diastolic volume and stroke volume actually tended to decrease after 3 months of training compared with control subjects, with no change at 12 months. In a similarly designed study of healthy older subjects (mean age, 64 years) in whom peak O2 increased by 26% over a 1-year training period, left ventricular systolic performance and peak exercise stroke volume and cardiac output were enhanced after conditioning.23 In the present study, the exercise stimulus was high given the low functional capacity of the population and extended to 1 year in a representative subset of the population. The absolute intensity, however, was somewhat less than can be applied to a noncoronary population.

The technique of percutaneous muscle biopsy enabled us to analyze biochemical and morphometric responses to conditioning that have not been studied previously in older coronary patients. As has been seen in younger and older healthy volunteers, activity of SDH, a rate-limiting enzyme of the tricarboxylic acid cycle, was increased by the conditioning program.45 49 50 Although the magnitude of the increase in SDH activity did not correlate with the increase in peak O2, the directional change was similar. This finding was not unexpected, as SDH is one of an array of oxidative enzymes that may adapt at different rates in response to exercise conditioning.45 49 In a recent study of exercise training in post–myocardial infarction patients, 31P NMR spectroscopy was used to assess overall oxidative metabolism in skeletal muscle after conditioning.51 At peak exercise, after conditioning, there was less depletion of phosphocreatinine and inorganic phosphates, which reflects a decrease in anaerobic metabolism during exercise. A close correlation was observed between improvement in phosphocreatinine accumulation and the increase in O2 max (r=.757).

The increased capillary density that we demonstrated probably contributes to the higher peak aerobic capacity by facilitating diffusion of bloodborne substrates, ie, glucose and oxygen, into the cytoplasm and mitochondria of the muscle cells, whereas the increase in cross-sectional volume of the muscle fibers in association with the increased oxidative enzyme activity would increase the capacity of the muscle cell to process substrate. The increase in muscle fiber size was associated with an increase in fat-free mass of 1.2 kg with conditioning in a subset of 10 of the 60 study patients. In contrast to studies in healthy subjects, glycogen stores in skeletal muscle were not increased after conditioning.52 This may have been due in part to the fact that we did not control dietary intake of carbohydrates before the biopsy53 or to a diminished absolute training stimulus.

The increase in capillary density was not associated with an increase in resting calf blood flow or in postischemic exercise hyperemic blood flow as measured by strain-gauge plethysmography. This may be because hyperemic blood flow is more dependent on dilatation of arteriolar and larger conductance vessels as opposed to capillary capacitance. Previous studies38 in middle-aged sedentary subjects showed that hyperemic blood flow and maximal calf conductance are closely related to peak aerobic capacity. Furthermore, in a conditioning study of sedentary middle-aged subjects, increases in maximal calf conductance were a major determinant of the increase in aerobic capacity over a 3-month training period.39 In our older population, we detected no relation between maximal calf conductance and peak aerobic capacity by linear regression analysis, nor were these measures altered by the conditioning process. This is in contrast to the results of Vaitkevicius et al26 in a healthy older population rigorously screened for coronary artery disease, in whom age-related increases in arterial stiffness were inversely related to physical fitness levels. We speculate that in the present study, age-related increases in the thickness and stiffness of both the left ventricle and peripheral arteries that supply skeletal muscle may have limited the cardiac and vascular response to the repeated volume loading of aerobic exercise.24 25 The presence of coronary heart disease and, in some subjects, subclinical peripheral vascular disease may have further exacerbated abnormalities of vascular and myocardial stiffness.27

The results of the present study may have clinical implications with regard to the design of training programs for older coronary patients. Since cardiac adaptations were not prominent even after an intense and prolonged program of aerobic exercise, it appears that a greater component of the training stimulus should focus specifically on skeletal muscle with the use of anabolic techniques such as resistance training. Although small studies54 55 56 57 58 of resistance or weight training in low-risk, middle-aged coronary patients demonstrated safety and effectiveness, this has yet to be studied in older coronary patients. Recent data from our laboratory demonstrate that in healthy subjects over the age of 65 years, "pure" weight training improves walking endurance without an increase in peak aerobic capacity.59 Studies60 61 62 of resistance training in healthy elders, including nonagenarians, demonstrated remarkable improvements in strength and endurance.

The implications of the present study are limited to the patient population under study: older coronary patients with relatively well-preserved left ventricular function (left ventricular ejection fraction >=30%) who were referred to an outpatient cardiac rehabilitation program. Older coronary patients not referred to cardiac rehabilitation programs may be less fit and less well educated than referred patients, which could influence exercise compliance, particularly over a 12-month period.48 Although only minimal physiological changes occurred beyond the initial 3 months of training, this does not imply that training should only be short-term; rather, a long-term program is necessary to maintain the improvements in functional capacity. Finally, we made no measurement of diastolic function before and after conditioning. The latter could be a determinant of exercise capacity independent of peak cardiac output, as has been suggested in patients with systolic dysfunction.

In summary, physiological adaptations to short-term and long-term aerobic exercise programs in older coronary patients are primarily localized to skeletal muscle, with only subtle adaptations of cardiac function. Accordingly, training programs that focus primarily on skeletal muscle may be particularly valuable in elderly patients and warrant further investigation.


*    Acknowledgments
 
This study was supported by a clinical investigator award from the National Institute on Aging (Dr Ades, No. K08-AG00426) and by a grant from the General Clinical Research Center of the University of Vermont (GCRC-RR109). The authors thank Jere Mitchell, MD, and Peter Snell, PhD, for their assistance in the design of this study.


*    Footnotes
 
Reprint requests to Philip A. Ades, MD, McClure 1, Cardiology, Medical Center Hospital of Vermont, Burlington, VT 05401.

Received September 19, 1995; revision received January 3, 1996; accepted January 7, 1996.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *References
 

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