Effects of physical training on cardiovascular function following myocardial infarction D. H. PATERSON, R. J. SHEPHARD, D. CUNNINGHAM, N. L. JONES, AND G. ANDREW Department of Preventive Medicine and Biostatistics, University of Toronto and Toronto Rehabilitation Centre, Toronto M5S lA1; Faculty of Physical Education and Department of Physiology, University of Western Ontario, London N6A 5Cl; Department of Medicine, McMaster University, Hamilton L8S 4J9; and School of Physical and Health Education, Queen’s University, Kingston, Ontario K7L 3N6, Canada
PATERSON, D.H.,R. LSHEPHARD, D. CUNNINGHAM,N. L. JONES, AND G. ANDREW. Effects of physical training on cardiovascular function following myocardial infarction. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47(3): 482-489, 1979.-Three to twelve (7.1 & 3.2) months after myocardial infarction, subjects under 54 (45.0 -+ 4.7) yr were assigned randomly to high-intensity (HIE, n = 37) or low-intensity (LIE, n = 42) exercise programs. Cardiac outputs (Q) during graded bicycle ergometer exercise were measured by a COz-rebreathing method on entry and after 6 and 12 mo of training. The initial exercise Q was low in relation to work load, due to a low stroke volume (SV). Over the year of training, the predicted maximal O2 intake of the HIE group increased significantly (from 26.0 to 30.3 ml* kg-’ emin-‘), while that of the LIE group showed no significant alteration. During the first 6 mo, the heart rate of the HIE group was significantly reduced at each work level. There was an associated widening of arteriovenous oxygen difference, but SV was unchanged. These findings were attributed to extracardiac factors, including a redistribution of blood flow, biochemical changes in the trained muscle, and a secondary reduction of sympathetic drive. Over the second 6 mo, the SV of the HIE group increased 10%; this may reflect an increase of intrinsic myocardial contractility that develops if high-intensity training is sustained. The LIE group showed no major changes of cardiovascular function over the year of observation. cardiorespiratory ity; arteriovenous
fitness; stroke volume; myocardial oxygen difference
482
CONDITIONING
The investigation formed part of the Ontario MultiCentre Exercise-Heart Collaborative Study. Details of the experimenta 1 design, the popula tion tested and the methods of data collectio n are given by Rechnitzer et al.
(26).
Subjects and Experimental
Groups
Subjects were male volunteers under 54 yr of age; 3-12 mo before entry to the study, they had sustained a myocardial infarction, documented by two of the following criteria: typical history, electrocardiographic changes, and increases of serum enzyme levels. Random assignment was made to a vigorous training program (highintensity exercise, HIE) or to a control group who received a homeopathic dose of light recreational activity (low-intensity exercise, LIE). Of 104 potential subjects, we excluded those receiving cardiac medications such as propranolol, and those with a poor effort tolerance (only one work load completed, or failure to reach an 02 intake (VOW) of 1.25 lemin-‘). Analysis is thus based on 79 1-yr adherents (HIE, n = 37; LIE, n = 42).
contractil-
Exercise Studies
is now widely utilized in the treatment of patients following myocardial infarction (MI). Substantial gains of cardiorespiratory fitness can be realized (1, 21, 30), and associated alterations in the cardiovascular response to exercise have been described (2, 6, 7, 9, 10, 15, 28). However, the relative importance of central and peripheral adaptations is disputed, and there is a paucity of information on long-term responses to training. Indeed, it is still uncertain how far abnormalities of myocardial function consequent on infarction can be corrected or compensated by an appropriate regimen of physical activity. Accordingly, a controlled study was undertaken to examine the cardiovascular adjustments that accompany gains in cardiorespiratory fitness when subjects with a well-documented myocardial infarction undertake 6 and 12 mo of physical conditioning. PHYSICAL
METHODS
Exercise tests were performed in air-conditioned laboratories (T, = 22.7 t 0.9”C). Subjects avoided meals and stimulants such as coffee, tea, cola, or cigarettes for 2 h prior to testing. At the first attendance, a simple bicycle ergometer test was performed. The work load was increased at 1-min intervals and heart rates were noted, exercise being stopped at a heart rate of 150 beats. min. The objectives of this procedure were 1) to habituate the subjects to exercise testing, 2) to establish the individual’s heart rate/work load rela tionship, and 3 It 0 provide a guide for exercise prescription. Methods of translating the bicycle ergometer result into an appropriate training distance and speed are detailed elsewhere All medication was stopped for at least 24 h prior to the second visit, when cardiorespiratory and metabolic responses to exercise were evaluated by a progressive
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0 1979 the American
Physiological
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CARDIOVASCULAR
TRAINING
AFTER
MYOCARDIAL
“stage II” test (17). An electrically braked “constant” work load ergometer was pedaled at 50-60 rpm using three settings designed to elicit heart rates of 110-120, 120-130, and 140-150 beatsmin-‘, respectively. Individual loadings were sustained for 6-7 min with 2-min intervals of loadless pedaling or rest between successive work levels. All data were recorded under “steady-state” conditions: here defined as either heart rate constant to t 5 beats. min-’ and a mixed expired CO2 concentration constant to t 0.2%, or a minimum of 5 min exercise at a given load. Stage II testing was repeated 6 and 12 mo after completion of the entry measurements. Quality-control techniques (Jones and Kane, in preparation) were employed to establish the validity of data obtained at the participating laboratories. Cardiovascular
Measurements
Steady-state oxygen intake and CO2 output were determined by an open-circuit technique (17, 32). Inspired gas volume, breathing frequency, and heart rate were measured over a I-min period. Expired gas was sampled from a mixing box for analysis of expired CO2 concentration of (FE~o,) (infrared analyzer) and expired 02 concentration (FEN,) (paramagnetic analyzer) and at the mouthpiece for end-tidal CO2 concentration (FETED,). Immediately following the measurements of gas exchange, the oxygenated mixed venous CO2 pressure (PVco,) was determined by a rebreathing method (17). v02 and CO2 output (Vcoz) were calculated at STPD. Arterial CO2 pressure (Pace,) was obtained from the equation (25) Pac0,
= PETCO,+ 4.4 + 0.03 f, + 0.0023 VT
- 0.09 PEco,
rTod
where f, is the respiratory frequency and VT the tidal volume. PVco, was estimated by applying an empirical correction for a gas-blood PCO~difference (17) PVco, = Pbagco, - (0.024 Pbagco, - 11.0)
483
INFARCTION
CTod
where Pbagco, is the partial pressure of CO2 in the rebreathing bag. Data were corrected to a hemoglobin of 15 go100 ml-’ and an assumed arterial 02 saturation of
95% (17). The reproducibility and reliability of the cardiac output data thus obtained is similar to that reported for dyedilution and direct Fick methods (11, 17, 35). The coefficient of variation is -5.7%, without systematic error. For the purpose of the present experiments, all cardiac output determinations were subject to interlaboratory quality control checks at least once per year. Training The HIE subjects followed a regimen of increasing endurance exercise (8, 21). Their walk/jog prescription progressed in duration from 30 to 45 min. Intensity was normally at a heart rate and speed corresponding to 6570% of maximal 02 intake (\j02 max),but was scaled appropriately downward in individuals whose activity was limited by angina or specific electrocardiographic signs.
The prescribed exercise was carried out a nominal 5 times/wk (as monitored by an exercise-log), 1 or 2 sessions/wk being performed in a supervised group setting. The LIE program simulated that of the HIE group, except that activity (in the form of weekly recreational games) was held to a level that provided a negligible amount of training (less than 50% VOWmax). Data Analyses Cardiovascular variables were expressed at common or extrapolation of data never exceeded 0.25 l*min-‘. Not all laboratories carried testing to a symptom- or sign-limited . vo zmax. Accordingly, it was necessary to predict such values from the heart rate and v02 at the highest work load sustained for at least 3 min, using a computer solution of the Astrand nomogram (32). Earlier experiments (20) suggest that this approach is valid in postcoronary patients who are able to participate in an exercise training program. Statistical analysis include analysis of variance between groups and over time (2 x 3 ANOVA), with post-hoc t tests of significance. v02 of 1.00, 1.25, and 1.50 lgmin-‘. Interpolation
RESULTS
Initial
Characteristics
Subjects with a mean age of 45.0 t 4.7 yr were first seen 7.1 t 3.2. mo after infarction. Initial characteristics (Table 1) were closely similar in HIE and LIE groups, except that the HIE subjects had a significantly shorter hospital stay at the time of infarction. The body mass (initalIy - 80 kg) showed no change in either group over the year of observation. Residual angina was reported by 24% of the experimental sample (compared with 28% in the initial population of 104 volunteers); attrition of angina1 subjects was greater in the LIE group. The initial predicted VO 2maxwas comparable for the HIE and LIE groups (27.5 and 28.3 n&kg-‘emin-‘, respectively), and heart rates at a given VOW agreed to within 3-5 beats. min-’ (Table 2). The initial cardiac output at a given To2 was slightly lower than was found in a small sample (n = 9) of healthy middle-aged men tested by the same methodology in the Toronto laboratory (Fig. 1). The submaximal exercise heart rate was also higher, and the stroke volume was TABLE
1. Initial characteristics of subjects Variable
Age,
yr
Ht, cm Body mass, kg Hb, gel00 ml-’ Months post-MI Hospital stay, days Angina n % with residual angina Values intensity subject. jects.
HIE Group
44.5 175.0 79.7 15.9 7.3 17.8
t 2 t, t t t,
10 27.0
(n = 37)
4.0 6.6* 10.4 1.3 2.7 7.6-f*
LIE Group
45.5 175.7 80.2 15.8 6.9 23.1
t_ t t t t t
(n = 42)
5.3 6.1 10.1 1.3 3.7 8.6#
9 21.4
are means t, SD. HIE, high-intensity exercise; LIE, low*n = 36; height exercise. not recorded for one t n = 34; period of hospitalization unknown for two sub$ Significant difference between groups (P < 0.05).
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484
PATERSON
some 10% smaller than in the normals. HIE and LIE groups did not differ respect to these variables. Training
However, data for significantly with
Response
Monitoring of supervised training sessions and examination of the exercise logs established that subjects adhered closely to their prescribed programs. The attendance at supervised sessions averaged 80% for the subjects in the present study. The HIE group showed significant gains of cardiorespiratory fitness, with a 5-9% reduction of heart rate at a fixed submaximal Vo2 (Table Z), a 13.1% increase of predicted Vo 2 maxat 6 mo, and 14.9% increase of predicted Vo 2 maxat 1 yr. In contrast, data for the LIE group remained unaltered over this period.
2. Cardiorespiratory HIE and LIE groups
fitness of
TABLE
fh, beats-min 1.00
1.25 HIE group
Initial 6mo
103
lyr
w
% Change 6mo
-4.9 -4.9
lyr
\jop, l- min-’ 1.00
1.25 LIE group
(n = 37)
118
923*
-‘, at Given 1.50
99 102
132 122*
110* 109t
120-f
-6.8 -7.6
-7.6
-3.0
-9.1
-5.1
94*t
1.50 (n = 42)
113 115
126 128
113
126
+1.8
+1.6
0.0
0.0
Pred %‘o, max I-min. HIE group
Initial 6mo
27.5
lyr
31.6
t
5.7
31.1 k 5.0*
% Change 6mo
t
4.5-t
ml-kg-‘-mir-’
(n = 37)
2.18 2.45 2.49
+13.1 + 14.9
lyr
’
-+ 0.47 k 0.46* t 0.45-f
28.3 27.8 28.0
l-mine’
LIE group
(n = 42)
zk 4.5 k 4.3 t 5.5
2.26 2.22 2.21
+12.4
-1.8
+14.2
-1.1
t 0.39 t 0.35 t, 0.42
Cardiovascular
ET
AL.
Changes
In the first 6 mo of training, the HIE group showed a typical exercise bradycardia. Heart rate (fh) reductions of 5-10 beats l rein-’ were statistically significant at all v02 levels (Fig. 2). Stroke volume (SV) remained unchanged; rather, the arteriovenous (a-v) 02 difference was widened, and cardiac output for a given v02 was reduced by 5-8%. From the 6th to the 12th mo, SV increased by 6-ll%, this change being significant at a v02 of 1.5 lmin-’ and also at 1.75 lgmin-l in those reaching this work load. Over the same period, fh showed an insignificant decline of 3 beatsmin-‘, and there was an insignificant decline in the a-v 02 difference during submaximal effort (Fig. 2) *The only statistically significant changes in the LIE group were seen after 1 yr, when there was a 4% reduction of fh at low work loads (VOWof 1 lemin-‘) and a 3-8% decrease of SV at high work loads (v02 of 1.5 and 1.75 10 min-‘). There was also a trend toward a reduction of cardiac ouput and a broadening of a-v 02 difference in moderate to heavy work (Fig. 3), but these were not found to be significant. The obvious differences between the HIE and LIE groups were the significant reduction of fh and increase of SV in the subjects who undertook vigorous training (Fig. 4). The maximum SV was reached at the lightest work load in all tests. In the HIE group, values increased from 99 ml on entry, to 101 ml at 6 mo, and 109 ml at 1 yr, whereas the SV volume of the LIE group remained unchanged at - 102 ml. DISCUSSION
Sample Selection
-1.8 -2.2
fh, mean heart rate; Pred 00 2 ,,,=, mean predicted maximal 02 intake t SD; HIE, high-intensity exercise; LIE, low-intensity exercise. * Significant change (P < 0.05) over 6-mo period. t Significant change (P < 0.05) over I-yr period.
Participants in the study were selected according to specific entry criteria (26). The average age was 2-6 yr younger than in unselected subjects admitted to a Scandinavian hospital (30)) but other characteristics including height, weight, heart volume, localization of the infarct,
14.0n 75 g
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12.0-
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E 901
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.
L
+I
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.
.*
I I.50
1 I.75
\io, (l~min-‘) FIG. 1. Relationship between output (Q) and B, stroke volume range of normal values found in corresponding reported range for
oxygen intake (Vo,) and A, cardiac (SV). Cross hatched area represents the literature; dotted lines demarcate subjects following mvocardial infarc-
60LI: 5,
I 1.00
I I.25
I I.50
I I.75
\jo2 (l*minw’) tion. XX CS, average of values for all subjects participating in study (n = 79; break in line indicates reduction of sample size to n = 56 9 healthy middle-aged subjects at Vo2 1.75 l*min-‘). A -----A Normals, tested in the Toronto Laboratory. Values are means & SE.
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CARDIOVASCULAR
TRAINING
AFTER
MYOCARDIAL
485
INFARCTION l50-
H.I.E. GROUP -o-Initial -a e--6 months . ..*e . .. . I year * significant 6 mo. change significant I yr. change
t
B L
-7 140.a z g
1 .-c E
n=21
-I3 12.0G
IO-
10.0 -
loo-
’
i
’ 1.25
’
’
’
’
I.50’
’
’
1 ’
."..*
0” I> &J l20-
II.0 -
’
4
l30-
11’
1.75 ‘
I
++I00 .
I
i
Vo, (l-mid) 145r
I
I
I
i
1.25
11
11
11
1.50
1.75
Co2 (5. mid) II
c W-0
I IO
,A .....
l ..’
.+
3 105 -5 z
100 ,
lO5-
95-
Ir %I’100 ’
’
’
’
’
I .25
’
’
’
’
’
1.50
’
’
’
’
’ 1.75
JT 5’
1.00
”
”
”
1.25
90, (1. min.‘)
”
”
1.50
”
”
’
I75
i!ot (1. min”)
FIG. 2. Changes in cardiovascular response to exercise with highintensity (HIE) training. Data for A, cardiac output (Q), B, arteriovenous oxygen difference (a-v 02 diff), C, heart rate (fh), and D, stroke
volume (broken
and frequency of residual angina were much as in the unselected samples of “postcoronary” patients. Exclusion of subjects on “cardiac” medication, and those with a poor work tolerance (~OZ < 1.25 lmin-‘) presumably eliminated the more severely diseased of our volunteers, although HIE and LIE groups would have been affected equally by this selective process. The shorter average hospital stay might suggest that some of the HIE patients had less severe disease than members of the LIE group. However, this may merely reflect differences in the practice of referring hospitals. Certainly, the initial predicted VOW maxwas similar for the two groups, although the final proportion of subjects with angina was greater in the HIE than in the LIE group; this last finding would inevitably have reduced the average potential for training in the HIE subjects (2). Our initial figures for predicted VOW maxwere about 10% higher than the symptom-limited Vozrnax observed in some previous large studies (4, 30). The method of predicting To2 maxmay have contributed to this difference. In some instances, the maximum fh of the postcoronary patient can be reduced by either symptoms or chronotropic factors (20). Nevertheless, maximum tests have
shown that the majority of those attending an exercise rehabilitation program can reach a normal age-related maximum fh (ZO), so that predicted data agree well with direct measurements. Other predicted values from our Toronto laboratory have shown a VOW maxof 25.1 t 7.7 ml* kg-‘*min-’ in 319 subjects who were seen a few months after infarction (Shephard and Kavanagh, unpublished data). Probably the main reason for the somewhat higher VOW maxin the present series was our deliberate exclusion of subjects receiving medication or showing a poor work tolerance. There is little evidence that exercise in itself led to a selective attrition of severely diseased patients from the HIE sample. Indeed, as noted above, the adherent HIE group finally contained a larger proportion of subjects with angina than the LIE group.
at Vo2
(SV) plotted Lines indicate = 1.75 1 mm’).
Cardiovascular
in relation reduction
to interpolated oxygen intake (VOW) of sample size from 37 to 21 subjects
Status after Myocardial
Infarction
Our initial cardiovascular data are in accord with previous reports of a hypokinetic (19) or normokinetic (5, 19, 23, 24, 25) circulation, stroke volume failing to show the normal increase with progression from moderate to
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486
PATERSON L.I.E. GROUP -CJ-Initial - ‘e-6 months ... . .a . .. ..I year * significant 6 mo. change t significant I yr. change
ET
AL.
8 . . ..a /a ---Id
,...m n= 35
n=42
Lv
’
1100
’
’
’
’
’
’
’
’
’
’
’
’
1.50 i/o,
l45-
’
1.25
’ I75
1.00
-
c
1.75
(l-mid)
0
ll5-
110 -
l25-
-
.-c E
1.50 V0,
135 -
i
1.25
( 1. min-’ )
lO5-
2 s *too-
-
EC ll5*
lO5-
_ -0
O---O-Ou---...2..***....... - -- -IL-...*....s-e.... -4 -- ‘o--a-.. ......-,.*-..-.....-*--.......*. -....
95-
-4 a...
.g
90 -
L’
1.00
’
’
’
’
’
I 25
’
i/o,
’
’
’
’
1.50
’
’
’
’
its
a* Y
I
I
I
I
I
00
I
““‘1’
11
I 25
(1. min-‘)
150 i/o,
(1 md)
3. Changes in the cardiovascular response to exercise with lowintensity (LIE) training. Data for A, cardiac output (Q), B, arteriovenous oxygen difference (a-v 02 diff), C heart rate (fh), and D, stroke
volume (SV) plotted (broken Line indicates at Vo2 = 1.75 lDmin-I).
heavy work (4, 28). Such changes may be the effects of disease or the imposed bed rest and subsequent restriction of activity. Braunwald et al. (3) noted that a sustained or transient regional loss of myocardial contractility could depress overall left ventricular function, with a reduction of stroke volume. In the present study, myocardial status was assessedby various procedures such as echocardiography, angiography, and electrocardiography at cooperating hospitals, but there were few reports of asynergic or akinetic areas in the heart wall; a recent survey of the Toronto patients (Shephard and Kavanagh, in preparation) showed 16 out of 610 with radiographic evidence of aneurysm, 25 out of 610 with cardiac enlargement, and 163 out of 610 with more than 0.2-mV depression in the ST segment of the electrocardiogram at 75% VOW max. Attempts to relate the behaviour of stroke volume to initial or final clinical status yielded no significant relationships. Furthermore, Saltin et al. (29) have shown a marked (30%) reduction of exercise stroke volume when normal subjects are confined to bed; this takes several weeks of intensive training to correct. A similar phenomenon, induced by hospitalization and
subsequent inactivity, thus seems the most likely explanation of the present findings.
FIG.
in relation reduction
’
I 75
to interpolated oxygen intake (HOP) of sample size from 42 to 35 subjects
Response to Training Gains of maximal oxygen intake. The gains of VOW max in the HIE group were smaller than in some (7, 10, 15, 18, 28) but not all (1, 2) previous studies of exercised postcoronary patients. The main gain of VOZ maxoccurred over the first 6 mo of training. Ferguson et al. (13) and Sanne (30) have commented on a similar plateauing of the training response. Factors that may have limited the observed response to training were 1) the commencement of observations 7 mo after infarction, 2) our reliance on a “home” prescription, with only 1 or 2 supervised sessions/wk, and 3) a possible underestimation of the necessary jogging training when prescribed on the basis of a cycle ergometer test. Nevertheless, 1-yr gains of VOZ maxcompared closely with the l&20% gains reported by Kavanagh et al. (2l), and the final predicted VOW maxof 30 ml. kg-’ emin-’ also
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CARDIOVASCULAR A
TRAINING
AFTER
MYOCARDIAL
INFARCTION
487
was offset by an enhancement of intrinsic myocardial contractility (8) or an increase of end-diastolic volume. Rousseau et al. (28) noted that, in the absence of conditioning, stroke volumes increased in the first few months after infarction. The opposing influences of decreased sympathetic drive, increased intrinsic contractility, and increased end-diastolic volume could explain why various authors have seen responses ranging from a 6% decrease to an 18% increase of stroke volume. As in earlier studies of postcoronary patients (6, 15), the training-induced reduction of cardiac output and t t widening of arteriovenous oxygen difference tended to be 125 135 105 I15 I25 135 largest at light work loads. More data are needed to 95 f h ( b.mln”) fh (b.min”) confirm the trend, although this would support the hyFIG. 4. Relationship between stroke volume (SV) and heart rate (fh) pothesis that in heavy work the tendency to a reduction in A, high-intensity (HIE) training group and B, low-intensity (LIE) of stroke volume was offset by a lesser peripheral resisttraining group. Lines show mean SV at mean fh for each work load. ance as muscles became strengthened through training (32). Others (6,9,10,15) have noted larger gains of stroke agreed well with previous estimates of 30.6 nil. kg-‘. volume in heavy than in light work; this reflects partly a lowering of the relative work load with training, and min-’ after 6 mo training (18) and 31.3 or 33.4 ml. kg-‘. min-’ after 12 mo training (21, 28). The experimental partly an improved ability to sustain stroke volume as design appeared to be appropriate in that the HIE group maximum effort is approached. showed a substantial gain of fitness, whereas the LIE SECOND 6 MO. In the second 6 mo of training, there was group showed no more than a slight reduction of heart a 6-11s increase of stroke volume seen particularly in moderate through heavy work. Previous investigators rate in light work. Cardiovascular changes. FIRST 6 MO. The classical have not followed the cardiac outputs of trained posteffect of training upon the cardiovascular response to coronary patients for longer than 6 mo; nevertheless, studies have also observed an submaximal exercise is a decrease of heart rate with an some of the shorter-term increase of stroke volume, this response being particuincrease of stroke volume (2, 7,9, 15, 28). This cannot be larly evident in middle-aged men (16). Subjects on the attributed to a continuation of the natural recovery procHIE program demonstrated the anticipated bradycardia, ess, since in our experiments the LIE group showed a but without a concomitant increase of stroke volume. small decrease of stroke volume over the same period. Other studies of early training responses in both normal Possible explanations of the gain in the HIE group insubjects and postcoronary patients have had similar findclude 1) correction of the asynchronous contraction seen ings (1, 7, 10). As in our investigation, a widened arteriimmediately after infarction (3), 2 ) increases of contracovenous oxygen difference and a decrease of cardiac tility due to myocardial hypertrophy or changes in myoutput have generally accompanied the decline of heart ocardial metabolism (29)) and 3) peripheral changes. In rate. A more hypokinetic circulation following training view of the heart rate data, an alteration of cardiac has been taken to indicate an alteration of circulatory sympathetic or parasympathetic discharge seems unregulation (12,27) with a redistribution of cardiac output likely at this stage of training. At first inspection, an increase of myocardial contractility might seem a disad(7) The reduction of exercise heart rate implies either a vantage for a patient with a restricted coronary blood local change in the responsiveness of the pacemaker, or flow. However, in practice the added cost of the increased a reduction of the sympathetic drive to the heart. Possistroke volume is probably more than offset by the oxyble explanations of the latter include 1) a lessening of gen-sparing effect of a slower heart rate (22). The incortical drive to the vasomotor center (34), 2) a reduction crease of stroke volume is apparently accomplished withof cortical activation secondary to hypertrophy of slow out an increase of left ventricular dimensions (which twitch fibers (27), 3) reduction of blood flow from skin to would increase myocardial oxygen demands through the muscle (32), 4 ) easier perfusion of the active muscles Laplace relationship), and myocardial 02 demand may secondary to an increase in their maximum voluntary be further reduced as localized paradoxical movement of force (32), and 5) an increased peripheral extraction of the ventricular wall decreases (14). Finally, myocardial oxygen due to gains in muscle oxidative capacity (6). hypertrophy may reduce the tension per unit cross secLean mass did not change significantly. We may thus tion of ventricular wall, and thus the tension work load infer that there was little muscle hypertrophy, and that per gram of myocardium (33). Calculations of both the factors (2) and (4 ) probably contributed little to the rate-pressure product and the triple product support the observed response. Critics of factor (5) have noted that view that training reduces myocardial oxygen consumpblood leaving the active muscles is almost devoid of tion in the postcoronary patient (7, 8, 10, 15, 18). oxygen prior to the commencement of training (32). Any Clausen (6) and Degre et al. (9) have emphasized the change of sympathetic drive must thus be attributed to potential contribution of a peripherally mediated defactors (1) and (3). crease of total peripheral resistance (TPR) to the late Maintenance of stroke volume in the present study (as increase of stroke volume. There are several possible in other reports, e.g., Refs. 2, 9, 10) implied that the mechanisms. A reduction of general sympathetic vasonegative inotropic effect of a lessened sympathetic drive constrictor tone might decrease TPR, with increased H.I.E. GROUP -o-
L.I.E. GROUP -0InltkA --o--6months . . . . . m . . . . , year
lndd
--e--6moMhs -.......
PATERSON, D.H.,R. LSHEPHARD, D. CUNNINGHAM,N. L. JONES, AND G. ANDREW. Effects of physical training on cardiovascular function following myocardial infarction. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47(3): 482-489, 1979.-Three to twelve (7.1 & 3.2) months after myocardial infarction, subjects under 54 (45.0 -+ 4.7) yr were assigned randomly to high-intensity (HIE, n = 37) or low-intensity (LIE, n = 42) exercise programs. Cardiac outputs (Q) during graded bicycle ergometer exercise were measured by a COz-rebreathing method on entry and after 6 and 12 mo of training. The initial exercise Q was low in relation to work load, due to a low stroke volume (SV). Over the year of training, the predicted maximal O2 intake of the HIE group increased significantly (from 26.0 to 30.3 ml* kg-’ emin-‘), while that of the LIE group showed no significant alteration. During the first 6 mo, the heart rate of the HIE group was significantly reduced at each work level. There was an associated widening of arteriovenous oxygen difference, but SV was unchanged. These findings were attributed to extracardiac factors, including a redistribution of blood flow, biochemical changes in the trained muscle, and a secondary reduction of sympathetic drive. Over the second 6 mo, the SV of the HIE group increased 10%; this may reflect an increase of intrinsic myocardial contractility that develops if high-intensity training is sustained. The LIE group showed no major changes of cardiovascular function over the year of observation. cardiorespiratory ity; arteriovenous
fitness; stroke volume; myocardial oxygen difference
482
CONDITIONING
The investigation formed part of the Ontario MultiCentre Exercise-Heart Collaborative Study. Details of the experimenta 1 design, the popula tion tested and the methods of data collectio n are given by Rechnitzer et al.
(26).
Subjects and Experimental
Groups
Subjects were male volunteers under 54 yr of age; 3-12 mo before entry to the study, they had sustained a myocardial infarction, documented by two of the following criteria: typical history, electrocardiographic changes, and increases of serum enzyme levels. Random assignment was made to a vigorous training program (highintensity exercise, HIE) or to a control group who received a homeopathic dose of light recreational activity (low-intensity exercise, LIE). Of 104 potential subjects, we excluded those receiving cardiac medications such as propranolol, and those with a poor effort tolerance (only one work load completed, or failure to reach an 02 intake (VOW) of 1.25 lemin-‘). Analysis is thus based on 79 1-yr adherents (HIE, n = 37; LIE, n = 42).
contractil-
Exercise Studies
is now widely utilized in the treatment of patients following myocardial infarction (MI). Substantial gains of cardiorespiratory fitness can be realized (1, 21, 30), and associated alterations in the cardiovascular response to exercise have been described (2, 6, 7, 9, 10, 15, 28). However, the relative importance of central and peripheral adaptations is disputed, and there is a paucity of information on long-term responses to training. Indeed, it is still uncertain how far abnormalities of myocardial function consequent on infarction can be corrected or compensated by an appropriate regimen of physical activity. Accordingly, a controlled study was undertaken to examine the cardiovascular adjustments that accompany gains in cardiorespiratory fitness when subjects with a well-documented myocardial infarction undertake 6 and 12 mo of physical conditioning. PHYSICAL
METHODS
Exercise tests were performed in air-conditioned laboratories (T, = 22.7 t 0.9”C). Subjects avoided meals and stimulants such as coffee, tea, cola, or cigarettes for 2 h prior to testing. At the first attendance, a simple bicycle ergometer test was performed. The work load was increased at 1-min intervals and heart rates were noted, exercise being stopped at a heart rate of 150 beats. min. The objectives of this procedure were 1) to habituate the subjects to exercise testing, 2) to establish the individual’s heart rate/work load rela tionship, and 3 It 0 provide a guide for exercise prescription. Methods of translating the bicycle ergometer result into an appropriate training distance and speed are detailed elsewhere All medication was stopped for at least 24 h prior to the second visit, when cardiorespiratory and metabolic responses to exercise were evaluated by a progressive
0161-7567/79/0000-0000$01.25
Copyright
0 1979 the American
Physiological
Society
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CARDIOVASCULAR
TRAINING
AFTER
MYOCARDIAL
“stage II” test (17). An electrically braked “constant” work load ergometer was pedaled at 50-60 rpm using three settings designed to elicit heart rates of 110-120, 120-130, and 140-150 beatsmin-‘, respectively. Individual loadings were sustained for 6-7 min with 2-min intervals of loadless pedaling or rest between successive work levels. All data were recorded under “steady-state” conditions: here defined as either heart rate constant to t 5 beats. min-’ and a mixed expired CO2 concentration constant to t 0.2%, or a minimum of 5 min exercise at a given load. Stage II testing was repeated 6 and 12 mo after completion of the entry measurements. Quality-control techniques (Jones and Kane, in preparation) were employed to establish the validity of data obtained at the participating laboratories. Cardiovascular
Measurements
Steady-state oxygen intake and CO2 output were determined by an open-circuit technique (17, 32). Inspired gas volume, breathing frequency, and heart rate were measured over a I-min period. Expired gas was sampled from a mixing box for analysis of expired CO2 concentration of (FE~o,) (infrared analyzer) and expired 02 concentration (FEN,) (paramagnetic analyzer) and at the mouthpiece for end-tidal CO2 concentration (FETED,). Immediately following the measurements of gas exchange, the oxygenated mixed venous CO2 pressure (PVco,) was determined by a rebreathing method (17). v02 and CO2 output (Vcoz) were calculated at STPD. Arterial CO2 pressure (Pace,) was obtained from the equation (25) Pac0,
= PETCO,+ 4.4 + 0.03 f, + 0.0023 VT
- 0.09 PEco,
rTod
where f, is the respiratory frequency and VT the tidal volume. PVco, was estimated by applying an empirical correction for a gas-blood PCO~difference (17) PVco, = Pbagco, - (0.024 Pbagco, - 11.0)
483
INFARCTION
CTod
where Pbagco, is the partial pressure of CO2 in the rebreathing bag. Data were corrected to a hemoglobin of 15 go100 ml-’ and an assumed arterial 02 saturation of
95% (17). The reproducibility and reliability of the cardiac output data thus obtained is similar to that reported for dyedilution and direct Fick methods (11, 17, 35). The coefficient of variation is -5.7%, without systematic error. For the purpose of the present experiments, all cardiac output determinations were subject to interlaboratory quality control checks at least once per year. Training The HIE subjects followed a regimen of increasing endurance exercise (8, 21). Their walk/jog prescription progressed in duration from 30 to 45 min. Intensity was normally at a heart rate and speed corresponding to 6570% of maximal 02 intake (\j02 max),but was scaled appropriately downward in individuals whose activity was limited by angina or specific electrocardiographic signs.
The prescribed exercise was carried out a nominal 5 times/wk (as monitored by an exercise-log), 1 or 2 sessions/wk being performed in a supervised group setting. The LIE program simulated that of the HIE group, except that activity (in the form of weekly recreational games) was held to a level that provided a negligible amount of training (less than 50% VOWmax). Data Analyses Cardiovascular variables were expressed at common or extrapolation of data never exceeded 0.25 l*min-‘. Not all laboratories carried testing to a symptom- or sign-limited . vo zmax. Accordingly, it was necessary to predict such values from the heart rate and v02 at the highest work load sustained for at least 3 min, using a computer solution of the Astrand nomogram (32). Earlier experiments (20) suggest that this approach is valid in postcoronary patients who are able to participate in an exercise training program. Statistical analysis include analysis of variance between groups and over time (2 x 3 ANOVA), with post-hoc t tests of significance. v02 of 1.00, 1.25, and 1.50 lgmin-‘. Interpolation
RESULTS
Initial
Characteristics
Subjects with a mean age of 45.0 t 4.7 yr were first seen 7.1 t 3.2. mo after infarction. Initial characteristics (Table 1) were closely similar in HIE and LIE groups, except that the HIE subjects had a significantly shorter hospital stay at the time of infarction. The body mass (initalIy - 80 kg) showed no change in either group over the year of observation. Residual angina was reported by 24% of the experimental sample (compared with 28% in the initial population of 104 volunteers); attrition of angina1 subjects was greater in the LIE group. The initial predicted VO 2maxwas comparable for the HIE and LIE groups (27.5 and 28.3 n&kg-‘emin-‘, respectively), and heart rates at a given VOW agreed to within 3-5 beats. min-’ (Table 2). The initial cardiac output at a given To2 was slightly lower than was found in a small sample (n = 9) of healthy middle-aged men tested by the same methodology in the Toronto laboratory (Fig. 1). The submaximal exercise heart rate was also higher, and the stroke volume was TABLE
1. Initial characteristics of subjects Variable
Age,
yr
Ht, cm Body mass, kg Hb, gel00 ml-’ Months post-MI Hospital stay, days Angina n % with residual angina Values intensity subject. jects.
HIE Group
44.5 175.0 79.7 15.9 7.3 17.8
t 2 t, t t t,
10 27.0
(n = 37)
4.0 6.6* 10.4 1.3 2.7 7.6-f*
LIE Group
45.5 175.7 80.2 15.8 6.9 23.1
t_ t t t t t
(n = 42)
5.3 6.1 10.1 1.3 3.7 8.6#
9 21.4
are means t, SD. HIE, high-intensity exercise; LIE, low*n = 36; height exercise. not recorded for one t n = 34; period of hospitalization unknown for two sub$ Significant difference between groups (P < 0.05).
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484
PATERSON
some 10% smaller than in the normals. HIE and LIE groups did not differ respect to these variables. Training
However, data for significantly with
Response
Monitoring of supervised training sessions and examination of the exercise logs established that subjects adhered closely to their prescribed programs. The attendance at supervised sessions averaged 80% for the subjects in the present study. The HIE group showed significant gains of cardiorespiratory fitness, with a 5-9% reduction of heart rate at a fixed submaximal Vo2 (Table Z), a 13.1% increase of predicted Vo 2 maxat 6 mo, and 14.9% increase of predicted Vo 2 maxat 1 yr. In contrast, data for the LIE group remained unaltered over this period.
2. Cardiorespiratory HIE and LIE groups
fitness of
TABLE
fh, beats-min 1.00
1.25 HIE group
Initial 6mo
103
lyr
w
% Change 6mo
-4.9 -4.9
lyr
\jop, l- min-’ 1.00
1.25 LIE group
(n = 37)
118
923*
-‘, at Given 1.50
99 102
132 122*
110* 109t
120-f
-6.8 -7.6
-7.6
-3.0
-9.1
-5.1
94*t
1.50 (n = 42)
113 115
126 128
113
126
+1.8
+1.6
0.0
0.0
Pred %‘o, max I-min. HIE group
Initial 6mo
27.5
lyr
31.6
t
5.7
31.1 k 5.0*
% Change 6mo
t
4.5-t
ml-kg-‘-mir-’
(n = 37)
2.18 2.45 2.49
+13.1 + 14.9
lyr
’
-+ 0.47 k 0.46* t 0.45-f
28.3 27.8 28.0
l-mine’
LIE group
(n = 42)
zk 4.5 k 4.3 t 5.5
2.26 2.22 2.21
+12.4
-1.8
+14.2
-1.1
t 0.39 t 0.35 t, 0.42
Cardiovascular
ET
AL.
Changes
In the first 6 mo of training, the HIE group showed a typical exercise bradycardia. Heart rate (fh) reductions of 5-10 beats l rein-’ were statistically significant at all v02 levels (Fig. 2). Stroke volume (SV) remained unchanged; rather, the arteriovenous (a-v) 02 difference was widened, and cardiac output for a given v02 was reduced by 5-8%. From the 6th to the 12th mo, SV increased by 6-ll%, this change being significant at a v02 of 1.5 lmin-’ and also at 1.75 lgmin-l in those reaching this work load. Over the same period, fh showed an insignificant decline of 3 beatsmin-‘, and there was an insignificant decline in the a-v 02 difference during submaximal effort (Fig. 2) *The only statistically significant changes in the LIE group were seen after 1 yr, when there was a 4% reduction of fh at low work loads (VOWof 1 lemin-‘) and a 3-8% decrease of SV at high work loads (v02 of 1.5 and 1.75 10 min-‘). There was also a trend toward a reduction of cardiac ouput and a broadening of a-v 02 difference in moderate to heavy work (Fig. 3), but these were not found to be significant. The obvious differences between the HIE and LIE groups were the significant reduction of fh and increase of SV in the subjects who undertook vigorous training (Fig. 4). The maximum SV was reached at the lightest work load in all tests. In the HIE group, values increased from 99 ml on entry, to 101 ml at 6 mo, and 109 ml at 1 yr, whereas the SV volume of the LIE group remained unchanged at - 102 ml. DISCUSSION
Sample Selection
-1.8 -2.2
fh, mean heart rate; Pred 00 2 ,,,=, mean predicted maximal 02 intake t SD; HIE, high-intensity exercise; LIE, low-intensity exercise. * Significant change (P < 0.05) over 6-mo period. t Significant change (P < 0.05) over I-yr period.
Participants in the study were selected according to specific entry criteria (26). The average age was 2-6 yr younger than in unselected subjects admitted to a Scandinavian hospital (30)) but other characteristics including height, weight, heart volume, localization of the infarct,
14.0n 75 g
13.0-
.g
12.0-
l.. . . .. . . ... . . .. . .. .. . .
E 901
r
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t
10.0 .** .-_..*
.
L
+I
l.bo
I I.&
.
.*
I I.50
1 I.75
\io, (l~min-‘) FIG. 1. Relationship between output (Q) and B, stroke volume range of normal values found in corresponding reported range for
oxygen intake (Vo,) and A, cardiac (SV). Cross hatched area represents the literature; dotted lines demarcate subjects following mvocardial infarc-
60LI: 5,
I 1.00
I I.25
I I.50
I I.75
\jo2 (l*minw’) tion. XX CS, average of values for all subjects participating in study (n = 79; break in line indicates reduction of sample size to n = 56 9 healthy middle-aged subjects at Vo2 1.75 l*min-‘). A -----A Normals, tested in the Toronto Laboratory. Values are means & SE.
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CARDIOVASCULAR
TRAINING
AFTER
MYOCARDIAL
485
INFARCTION l50-
H.I.E. GROUP -o-Initial -a e--6 months . ..*e . .. . I year * significant 6 mo. change significant I yr. change
t
B L
-7 140.a z g
1 .-c E
n=21
-I3 12.0G
IO-
10.0 -
loo-
’
i
’ 1.25
’
’
’
’
I.50’
’
’
1 ’
."..*
0” I> &J l20-
II.0 -
’
4
l30-
11’
1.75 ‘
I
++I00 .
I
i
Vo, (l-mid) 145r
I
I
I
i
1.25
11
11
11
1.50
1.75
Co2 (5. mid) II
c W-0
I IO
,A .....
l ..’
.+
3 105 -5 z
100 ,
lO5-
95-
Ir %I’100 ’
’
’
’
’
I .25
’
’
’
’
’
1.50
’
’
’
’
’ 1.75
JT 5’
1.00
”
”
”
1.25
90, (1. min.‘)
”
”
1.50
”
”
’
I75
i!ot (1. min”)
FIG. 2. Changes in cardiovascular response to exercise with highintensity (HIE) training. Data for A, cardiac output (Q), B, arteriovenous oxygen difference (a-v 02 diff), C, heart rate (fh), and D, stroke
volume (broken
and frequency of residual angina were much as in the unselected samples of “postcoronary” patients. Exclusion of subjects on “cardiac” medication, and those with a poor work tolerance (~OZ < 1.25 lmin-‘) presumably eliminated the more severely diseased of our volunteers, although HIE and LIE groups would have been affected equally by this selective process. The shorter average hospital stay might suggest that some of the HIE patients had less severe disease than members of the LIE group. However, this may merely reflect differences in the practice of referring hospitals. Certainly, the initial predicted VOW maxwas similar for the two groups, although the final proportion of subjects with angina was greater in the HIE than in the LIE group; this last finding would inevitably have reduced the average potential for training in the HIE subjects (2). Our initial figures for predicted VOW maxwere about 10% higher than the symptom-limited Vozrnax observed in some previous large studies (4, 30). The method of predicting To2 maxmay have contributed to this difference. In some instances, the maximum fh of the postcoronary patient can be reduced by either symptoms or chronotropic factors (20). Nevertheless, maximum tests have
shown that the majority of those attending an exercise rehabilitation program can reach a normal age-related maximum fh (ZO), so that predicted data agree well with direct measurements. Other predicted values from our Toronto laboratory have shown a VOW maxof 25.1 t 7.7 ml* kg-‘*min-’ in 319 subjects who were seen a few months after infarction (Shephard and Kavanagh, unpublished data). Probably the main reason for the somewhat higher VOW maxin the present series was our deliberate exclusion of subjects receiving medication or showing a poor work tolerance. There is little evidence that exercise in itself led to a selective attrition of severely diseased patients from the HIE sample. Indeed, as noted above, the adherent HIE group finally contained a larger proportion of subjects with angina than the LIE group.
at Vo2
(SV) plotted Lines indicate = 1.75 1 mm’).
Cardiovascular
in relation reduction
to interpolated oxygen intake (VOW) of sample size from 37 to 21 subjects
Status after Myocardial
Infarction
Our initial cardiovascular data are in accord with previous reports of a hypokinetic (19) or normokinetic (5, 19, 23, 24, 25) circulation, stroke volume failing to show the normal increase with progression from moderate to
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486
PATERSON L.I.E. GROUP -CJ-Initial - ‘e-6 months ... . .a . .. ..I year * significant 6 mo. change t significant I yr. change
ET
AL.
8 . . ..a /a ---Id
,...m n= 35
n=42
Lv
’
1100
’
’
’
’
’
’
’
’
’
’
’
’
1.50 i/o,
l45-
’
1.25
’ I75
1.00
-
c
1.75
(l-mid)
0
ll5-
110 -
l25-
-
.-c E
1.50 V0,
135 -
i
1.25
( 1. min-’ )
lO5-
2 s *too-
-
EC ll5*
lO5-
_ -0
O---O-Ou---...2..***....... - -- -IL-...*....s-e.... -4 -- ‘o--a-.. ......-,.*-..-.....-*--.......*. -....
95-
-4 a...
.g
90 -
L’
1.00
’
’
’
’
’
I 25
’
i/o,
’
’
’
’
1.50
’
’
’
’
its
a* Y
I
I
I
I
I
00
I
““‘1’
11
I 25
(1. min-‘)
150 i/o,
(1 md)
3. Changes in the cardiovascular response to exercise with lowintensity (LIE) training. Data for A, cardiac output (Q), B, arteriovenous oxygen difference (a-v 02 diff), C heart rate (fh), and D, stroke
volume (SV) plotted (broken Line indicates at Vo2 = 1.75 lDmin-I).
heavy work (4, 28). Such changes may be the effects of disease or the imposed bed rest and subsequent restriction of activity. Braunwald et al. (3) noted that a sustained or transient regional loss of myocardial contractility could depress overall left ventricular function, with a reduction of stroke volume. In the present study, myocardial status was assessedby various procedures such as echocardiography, angiography, and electrocardiography at cooperating hospitals, but there were few reports of asynergic or akinetic areas in the heart wall; a recent survey of the Toronto patients (Shephard and Kavanagh, in preparation) showed 16 out of 610 with radiographic evidence of aneurysm, 25 out of 610 with cardiac enlargement, and 163 out of 610 with more than 0.2-mV depression in the ST segment of the electrocardiogram at 75% VOW max. Attempts to relate the behaviour of stroke volume to initial or final clinical status yielded no significant relationships. Furthermore, Saltin et al. (29) have shown a marked (30%) reduction of exercise stroke volume when normal subjects are confined to bed; this takes several weeks of intensive training to correct. A similar phenomenon, induced by hospitalization and
subsequent inactivity, thus seems the most likely explanation of the present findings.
FIG.
in relation reduction
’
I 75
to interpolated oxygen intake (HOP) of sample size from 42 to 35 subjects
Response to Training Gains of maximal oxygen intake. The gains of VOW max in the HIE group were smaller than in some (7, 10, 15, 18, 28) but not all (1, 2) previous studies of exercised postcoronary patients. The main gain of VOZ maxoccurred over the first 6 mo of training. Ferguson et al. (13) and Sanne (30) have commented on a similar plateauing of the training response. Factors that may have limited the observed response to training were 1) the commencement of observations 7 mo after infarction, 2) our reliance on a “home” prescription, with only 1 or 2 supervised sessions/wk, and 3) a possible underestimation of the necessary jogging training when prescribed on the basis of a cycle ergometer test. Nevertheless, 1-yr gains of VOZ maxcompared closely with the l&20% gains reported by Kavanagh et al. (2l), and the final predicted VOW maxof 30 ml. kg-’ emin-’ also
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CARDIOVASCULAR A
TRAINING
AFTER
MYOCARDIAL
INFARCTION
487
was offset by an enhancement of intrinsic myocardial contractility (8) or an increase of end-diastolic volume. Rousseau et al. (28) noted that, in the absence of conditioning, stroke volumes increased in the first few months after infarction. The opposing influences of decreased sympathetic drive, increased intrinsic contractility, and increased end-diastolic volume could explain why various authors have seen responses ranging from a 6% decrease to an 18% increase of stroke volume. As in earlier studies of postcoronary patients (6, 15), the training-induced reduction of cardiac output and t t widening of arteriovenous oxygen difference tended to be 125 135 105 I15 I25 135 largest at light work loads. More data are needed to 95 f h ( b.mln”) fh (b.min”) confirm the trend, although this would support the hyFIG. 4. Relationship between stroke volume (SV) and heart rate (fh) pothesis that in heavy work the tendency to a reduction in A, high-intensity (HIE) training group and B, low-intensity (LIE) of stroke volume was offset by a lesser peripheral resisttraining group. Lines show mean SV at mean fh for each work load. ance as muscles became strengthened through training (32). Others (6,9,10,15) have noted larger gains of stroke agreed well with previous estimates of 30.6 nil. kg-‘. volume in heavy than in light work; this reflects partly a lowering of the relative work load with training, and min-’ after 6 mo training (18) and 31.3 or 33.4 ml. kg-‘. min-’ after 12 mo training (21, 28). The experimental partly an improved ability to sustain stroke volume as design appeared to be appropriate in that the HIE group maximum effort is approached. showed a substantial gain of fitness, whereas the LIE SECOND 6 MO. In the second 6 mo of training, there was group showed no more than a slight reduction of heart a 6-11s increase of stroke volume seen particularly in moderate through heavy work. Previous investigators rate in light work. Cardiovascular changes. FIRST 6 MO. The classical have not followed the cardiac outputs of trained posteffect of training upon the cardiovascular response to coronary patients for longer than 6 mo; nevertheless, studies have also observed an submaximal exercise is a decrease of heart rate with an some of the shorter-term increase of stroke volume, this response being particuincrease of stroke volume (2, 7,9, 15, 28). This cannot be larly evident in middle-aged men (16). Subjects on the attributed to a continuation of the natural recovery procHIE program demonstrated the anticipated bradycardia, ess, since in our experiments the LIE group showed a but without a concomitant increase of stroke volume. small decrease of stroke volume over the same period. Other studies of early training responses in both normal Possible explanations of the gain in the HIE group insubjects and postcoronary patients have had similar findclude 1) correction of the asynchronous contraction seen ings (1, 7, 10). As in our investigation, a widened arteriimmediately after infarction (3), 2 ) increases of contracovenous oxygen difference and a decrease of cardiac tility due to myocardial hypertrophy or changes in myoutput have generally accompanied the decline of heart ocardial metabolism (29)) and 3) peripheral changes. In rate. A more hypokinetic circulation following training view of the heart rate data, an alteration of cardiac has been taken to indicate an alteration of circulatory sympathetic or parasympathetic discharge seems unregulation (12,27) with a redistribution of cardiac output likely at this stage of training. At first inspection, an increase of myocardial contractility might seem a disad(7) The reduction of exercise heart rate implies either a vantage for a patient with a restricted coronary blood local change in the responsiveness of the pacemaker, or flow. However, in practice the added cost of the increased a reduction of the sympathetic drive to the heart. Possistroke volume is probably more than offset by the oxyble explanations of the latter include 1) a lessening of gen-sparing effect of a slower heart rate (22). The incortical drive to the vasomotor center (34), 2) a reduction crease of stroke volume is apparently accomplished withof cortical activation secondary to hypertrophy of slow out an increase of left ventricular dimensions (which twitch fibers (27), 3) reduction of blood flow from skin to would increase myocardial oxygen demands through the muscle (32), 4 ) easier perfusion of the active muscles Laplace relationship), and myocardial 02 demand may secondary to an increase in their maximum voluntary be further reduced as localized paradoxical movement of force (32), and 5) an increased peripheral extraction of the ventricular wall decreases (14). Finally, myocardial oxygen due to gains in muscle oxidative capacity (6). hypertrophy may reduce the tension per unit cross secLean mass did not change significantly. We may thus tion of ventricular wall, and thus the tension work load infer that there was little muscle hypertrophy, and that per gram of myocardium (33). Calculations of both the factors (2) and (4 ) probably contributed little to the rate-pressure product and the triple product support the observed response. Critics of factor (5) have noted that view that training reduces myocardial oxygen consumpblood leaving the active muscles is almost devoid of tion in the postcoronary patient (7, 8, 10, 15, 18). oxygen prior to the commencement of training (32). Any Clausen (6) and Degre et al. (9) have emphasized the change of sympathetic drive must thus be attributed to potential contribution of a peripherally mediated defactors (1) and (3). crease of total peripheral resistance (TPR) to the late Maintenance of stroke volume in the present study (as increase of stroke volume. There are several possible in other reports, e.g., Refs. 2, 9, 10) implied that the mechanisms. A reduction of general sympathetic vasonegative inotropic effect of a lessened sympathetic drive constrictor tone might decrease TPR, with increased H.I.E. GROUP -o-
L.I.E. GROUP -0InltkA --o--6months . . . . . m . . . . , year
lndd
--e--6moMhs -.......
