Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.

OBJECTIVE: To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide. DESIGN: Randomized, double-blind, positive-controlled trial. SETTING: Nine medical center clinics. POPULATION: A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm. INTERVENTIONS: Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years. RESULTS: There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine. CONCLUSION: The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.

Effect of rate-adapting atrioventricular delay on stroke volume and cardiac output during atrial synchronous pacing.

The need to adjust atrioventricular delay relative to pacing rate in atrial synchronous pacemakers was assessed in eight subjects treated for complete heart block (mean age 61 +/- 3.4 years). First, an inverse relationship between heart rate and PR interval was confirmed in two groups of healthy subjects and one group of patients recovering from myocardial infarction. Due to the limitations of the available pacemakers this relationship could not be precisely reproduced. Subjects with pacemakers performed an initial exercise test on a bicycle ergometer to determine heart rate response; this information was used in part 2 to program atrioventricular delay relative to heart rate. During a second exercise test, a rate-adapting atrioventricular delay was compared to a constant atrioventricular delay of 200 ms at matched heart rates. Cardiac output was measured noninvasively by impedance cardiography. The results of part 1 showed an abnormal pattern in the response of stroke volume to exercise in seven subjects. Part 2 results demonstrated no significant difference (P greater than 0.05) between a rate-adapting atrioventricular delay and a constant delay of 200 ms for heart rate, stroke volume, cardiac output, blood pressure or Borg scale. A trend towards increased stroke volume with a rate-adapting atrioventricular delay was observed. Stroke volume was 13% larger with a rate-adapting atrioventricular delay of 125 ms at a heart rate of 125 beats/min. These results suggest that subjects with atrial synchronous pacemakers have a variable stroke volume response to exercise. It appears that in these subjects the ability to increase heart rate is the key factor for raising cardiac output during exercise.

Effects of hydraulic circuit training on cardiovascular function.

The effect of hydraulic circuit training (HCT) on cardiovascular (CV) function was assessed in 32 healthy middle-aged males (X age = 42.2 +/- 2.1 yr). Maximal aerobic power (VO2max), with simultaneous measurement of stroke volume (SV) and cardiac output (CO), by impedance cardiography, was assessed pre- and post-training. Subjects were randomly assigned to a nonexercising control group, a cycle training group (cycle), or one of the two HCT groups. Training groups participated in a 9 wk program, 3 d.wk-1. Subjects assigned to HCT exercised on a 9 station circuit, completing 3 circuits.d-1. Each circuit consisted of three 20 s work intervals at each station with a 1:1 work:rest ratio. One HCT group (HCTmax) completed the maximal repetitions possible (RM) during each work interval. The other HCT group (HCTsub) exercised at 70-85% of RM. Following training VO2max (ml.kg-1 min-1) was significantly increased in all training groups (18.0, 12.5, and 11.3% for cycle, HCTsub, and HCTmax groups, respectively; P less than 0.05). The increase in VO2max observed in the cycle group was significantly greater than that recorded by the two HCT groups (P less than 0.05). For all three training groups, the increase in VO2max was associated with increases in SVmax and COmax (P less than 0.05 for both). These findings suggest that both maximal and submaximal HCT programs can elicit improvements in cardiovascular fitness.

Endothelium-dependent relaxation to acetylcholine in the aorta of streptozotocin induced diabetic-rat and the BB-diabetic rat.

Experiments were designed to investigate the phenomenon of endothelium-dependent relaxation (EDR) to acetylcholine in two animal models of insulin dependent diabetes mellitus. Thoracic aortas obtained from streptozotocin diabetic rats and genetically diabetic biobreeding rats (BB rats) were used in this study. Concentration-effect curves to acetylcholine were carried out on aortic rings under isometric tension. Following the induction of diabetes with streptozotocin, half of the animals were treated with daily intermediate acting insulin and the other half maintained without insulin for a period of 12 weeks before the experiment. The diabetic BB rats were also maintained on insulin. The EDR to acetylcholine was not impaired in the aortas of streptozotocin diabetic rats (insulin treated as well as untreated) compared to nondiabetic controls. The scanning electron microscopic (SEM) appearances of the aortic endothelium did not differ among the three groups of animals. However, the EDR to acetylcholine was found to be impaired in the aortas of diabetic BB rats. (Maximum relaxation: 25.3 +/- 5.0% of the contraction to norepinephrine compared to 52.2 +/- 5.3% in controls.) The SEM appearances of the aortic endothelium in the diabetic BB rats were found to be abnormal with edema and loss of definition of cell margins compared to nondiabetic controls. The differences in EDR to acetylcholine seen between the two animal models of diabetes may be related to the different aetiologies of diabetes in the animals.

Reactive hyperemia in patients with Raynaud's phenomenon.

Our study was undertaken to demonstrate the efficacy of digital plethysmography using a strain gauge plethysmograph in the assessment of the reactive hyperemic response. We studied patients with Raynaud's phenomenon with and without associated connective tissue disorders. Reactive hyperemic response was examined in 27 normal subjects and 19 patients with Raynaud's phenomenon at 12-14 degrees C, 20-22 degrees C and 37-40 degrees C. In the normal subjects reactive hyperemia was greatest at 20-22 degrees C. In 19 patients with Raynaud's phenomenon, the pulse waves were smaller at 20-22 degrees C than in normal subjects and the response was seen in only 5 of 19 patients. At 12-14 degrees C reactive hyperemic response was usually absent and at 37-40 degrees C it was evident in 9 patients. Nifedipine was given to 11 patients (5 mg TID for 4 weeks) and in 10 of them, reactive hyperemic response was restored at 20-22 degrees C.

Impairment of endothelium-dependent relaxation: an early marker for atherosclerosis in the rabbit.

1. Cholesterol feeding of rabbits impairs the endothelium-dependent relaxation (EDR) evoked by acetylcholine (ACh) in the aorta. The experiments described in this paper were undertaken to examine the influence of age upon this phenomenon. 2. Rabbits aged 8 weeks and 46 weeks were fed a diet containing 2% cholesterol and other lipids for 4 weeks. Age-matched control animals were fed a standard rabbit diet. The concentrations of cholesterol and triglycerides in plasma were measured and the extent of atherosclerosis was estimated by staining the aortae with Sudan Red. Light and electron microscopy were undertaken also. 3. Rings of aorta were prepared for recording isometric tension. They were contracted with noradrenaline (NA) and EDR elicited by adding ACh. 4. The young rabbits showed weight gain, hypercholesterolaemia, prominent Sudan Red staining, together with scanning and transmission electron microscopic (SEM and TEM) features of cholesterol-induced atherosclerosis. The older animals showed significant weight loss and hypercholesterolaemia. The aortae of these animals showed no significant sudanophilia or light microscopic features of atherosclerosis. The SEM appearances were similar to the young animals fed cholesterol. 5. EDR to ACh was significantly impaired in both groups of cholesterol-fed rabbits. The maximal relaxations to ACh in young control and cholesterol-fed rabbits were 46.4 +/- 2.9% and 24.0 +/- 4.3% (mean +/- s.e. mean, n = 8, P less than 0.05) of the contractile response to NA (1 mumol 1(-1]. The corresponding results in the age control and cholesterol-fed rabbits were 31.8 +/- 3.9% and 9.1 +/- 1.5% (n = 9, P less than 0.05). 6. The young rabbits were far more susceptible to cholesterol-induced atherosclerosis than older animals and these changes were accompanied by loss of EDR. In the older animals and these changes were accompanied by loss of EDR. In the older animals the loss of the latter property was not accompanied by a significant degree of atherosclerosis although hypercholesterolaemia was present.

Evolution of the responses to exercise in left ventricular aneurysms after anterior wall acute myocardial infarction.

The evolution of the heart rate, blood pressure and electrocardiographic responses to exercise in 20 patients (group A) who exhibited echocardiographic evidence of left ventricular (LV) aneurysms after acute myocardial infarction (AMI) were examined. The responses were compared with those seen in 19 patients without LV aneurysms who were matched for age, gender and location of infarct (group B). Patients taking beta blockers were excluded from the study. It was found that the heart rate response to exercise was accentuated in group A at the time of discharge from hospital and that it became attenuated over 9 to 12 months. The blood pressure response was significantly increased over 9 to 12 months in group B. Persistence of ST elevation during exercise, 10 to 12 weeks after AMI, was diagnostic of an LV aneurysm. One year after AMI the sensitivity of ST elevation was 90%, specificity was 95% and the negative predictive value 90%.

The health care needs of southeast asian refugees.

Although the health of Southeast Asian refugees has been examined in the United States, the health of this population has not been studied in Canada, nor has there been an assessment of the effectiveness of the Canadian health care system in meeting the needs of this group. The authors of this article review the major health problems of Southeast Asian refugees as reported primarily by U.S. researchers, discuss the "theories of illness causation" of the refugees and the problems encountered in providing care to this group. They conclude that there is a need to examine the health of newly arrived refugees in Canada, assess their needs, and determine the adequacy of the existing health-care system to meet these needs.

Comparison of hemodialysis and hypertonic hemodiafiltration on cardiac function [corrected].

This study compared the acute and chronic effects on cardiac function of treatment with hypertonic hemodiafiltration (H HDF) and hemodialysis (HD). Cardiac function was assessed before, during and after a run of H HDF and HD using echocardiography and impedance cardiography in 10 patients in a randomized cross-over sequence, two months after stabilization on each treatment. Blood biochemistry was performed before and after each run. Ejection fraction and fractional shortening were significantly higher before the H HDF run, compared to the HD run, and this difference persisted during and after the treatment runs (both P less than 0.05). There was a corresponding significant difference in the increase of the velocity of circumferential fiber shortening and in the reduction of end systolic diameter during and after H HDF (P less than 0.05). Heart rate, stroke volume, cardiac output, systemic vascular resistance and mean arterial pressure did not differ significantly between the two treatments. Plasma calcium and bicarbonate were significantly higher (P less than 0.03) at the start of H HDF and this difference was enhanced at the end of the run. In conclusion, H HDF compared with HD, is associated with a better myocardial function in both the short and long term treatments. The evidence suggests that this may be due to improved levels of plasma calcium, bicarbonate, and/or the removal of an as yet unidentified myocardial toxin.

Endothelium-dependent relaxation in aorta of BB rat.

The study was undertaken to determine whether the phenomenon of endothelium-dependent relaxation was impaired in the spontaneously diabetic BB Wistar rat. Endothelium-dependent relaxation in the aorta of overtly diabetic animals was compared with that in nondiabetic BB rats. The relaxative responses were elicited in vitro to acetylcholine (-8.0 to -5.5 log M) and histamine (-7.0 to -3.0 log M) after precontraction with norepinephrine (-6.0 log M). The maximum relaxations produced by both acetylcholine and histamine expressed as percentages of the contractions to norepinephrine were significantly lower in diabetic than in nondiabetic rats. Scanning electron microscopy revealed that in diabetic BB rats there was consistent evidence of swollen cells, raised nuclei, and sloughing of nuclei in endothelial cells of the aorta. In nondiabetic animals these features were not evident. These findings suggest the presence of a functional and morphological defect in endothelial cells in the aorta of the BB rat.

Response to upright exercise after myocardial infarction.

The left ventricular response to upright bicycle exercise was studied in 39 unselected, non-beta blocked patients (mean(SEM) age 54.2(1.7)yr) (mean(SEM) resting ejection fraction 41.9(2.3)%) 8-10 weeks after myocardial infarction. Nine healthy, age matched, sedentary adult men were studied for comparison (mean(SEM) age 49.8(0.9)yr). The stroke volume and cardiac output were measured by impedance cardiography at rest and after each 3 min workload until symptom limited maximum. The patients were separated into three groups based on stroke volume response to graded exercise. Group 1 (n = 14) had a normal stroke volume response to increasing heart rate. In group 2 (n = 13) stroke volume increased initially then decreased by greater than 15% at a heart rate greater than 100-105 beats.min-1. In group 3 (n = 12) stroke volume failed to increase during exercise. In group 1 cardiac output and mean arterial pressure increased whereas vascular resistance decreased during exercise in a normal fashion. Group 2 had an increased mean arterial pressure and systemic vascular resistance throughout exercise while heart rate increased in a similar fashion to group 1 until work of greater than 70 W was undertaken, at which time heart rate increased in a curvilinear fashion and cardiac output was attenuated. Group 3 had an attenuated cardiac output and a higher heart rate during exercise. In this group of patients systemic vascular resistance failed to decrease normally during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nicardipine and diltiazem on alpha-adrenoceptor responses in canine saphenous veins.

The effects of calcium antagonists, diltiazem and nicardipine (-6.0 to -4.0 log mol/l), on the contractile responses to noradrenaline, methoxamine and BHT-920 in isolated canine saphenous vein rings, were studied with isometric tension recordings. Concentration-effect curves to the alpha-agonists were obtained in the control state and in the presence of diltiazem or nicardipine. Propranolol (-6.0 log mol/l) was present in the bath throughout. Diltiazem had no significant inhibitory effect on the responses mediated by all three agonists. Nicardipine (-5.0 and -4.0 log mol/l) produced a small but significant inhibitory effect on the responses to noradrenaline and methoxamine while it had no effect on the response to BHT-920. The effects of nicardipine were greatest on the responses to methoxamine. These calcium antagonists appeared to have only small post-synaptic inhibitory effects on the contractile responses to alpha-agonists in the canine saphenous vein with nicardipine exerting a greater inhibitory influence than diltiazem.

Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit.

The effect of feeding a diet supplemented with lipids and containing 2% cholesterol on the endothelium-dependent relaxation of rabbit aorta to acetylcholine was assessed. The effect of feeding a standard rabbit diet after an initial period of 2% cholesterol feeding was assessed also. Age-matched male, New Zealand white rabbits were fed either a 2% cholesterol diet or a standard rabbit diet. The animals were anesthetized with pentobarbitone sodium (25 mg/kg) and killed either at the beginning of the study (0 weeks) or at 4, 8, or 10 weeks. The animals in the reversal study were fed the 2% cholesterol diet for 6 weeks and killed after an additional 14 and 32 weeks on standard diet. The extent of atherosclerosis in the aorta was assessed by Sudan Red staining, estimation of tissue cholesterol, and light and electron microscopy. The relaxation response to acetylcholine was measured in rings of the thoracic aorta following precontraction with norepinephrine (-6.0 log mol/l). The relaxation was significantly impaired in aortas from rabbits fed the 2% cholesterol diet compared to aortas from animals fed the standard diet. The impairment of relaxation was apparent as early as 4 weeks after the start of the 2% cholesterol diet and remained impaired over the next 6 weeks. No improvement in endothelium-dependent relaxation was seen in rabbits on the reversal diet for 14 and 32 weeks. Thus, endothelium-dependent relaxation is attenuated in animals fed a 2% cholesterol diet, and the loss of relaxation persists for at least 32 weeks after the animals are returned to a standard diet.

Importance of considering ventricular function when prescribing exercise after acute myocardial infarction.

This investigation was undertaken in patients who had an acute myocardial infarction 12.6 +/- 0.4 months earlier to determine, using conventional methods, the nature of stroke volume changes during training regimens. Twenty-seven patients (mean age 52 +/- 2 years; rest ejection fraction 49 +/- 2%; New York Heart Association functional class I or II) and 9 normal, age-matched sedentary control subjects (mean age 50 +/- 1 years) exercised in the upright position on a bicycle ergometer. Stroke volume was measured by impedance cardiography at rest and after each workload. Ten patients (group A) had a stroke volume response similar to that of the normal sedentary subjects. In 8 patients (group B) the stroke volume increased initially, then decreased (more than 15%) at heart rates (HRs) greater than 100 to 105 beats/min. Nine patients (group C) had a flattened stroke volume response throughout exercise. Training HR determined by conventional methods corresponded to a maximal stroke volume in the normal subjects. Training HR in group A corresponded to a stroke volume that was maximal or near-maximal. Training HR in group B corresponded to a maximal or diminishing stroke volume. In group C, the training HR corresponded to a stroke volume no different from that at rest. Thus, training HR determined by conventional methods based solely on the chronotropic responses to exercise may place patients who have abnormal stroke volume responses to upright exercise in a situation during training sessions in which an inappropriately high HR, excessive fatigue or silent ischemia may develop.

Tetrodotoxin-resistant relaxation to transmural nerve stimulation in canine saphenous veins: a possible neural origin.

Transmural nerve stimulation following sympathetic (guanethidine 10(-4) mol/L, phenoxybenzamine 2 X 10(-5) mol/L, propanolol 2 X 10(-6) mol/L) and muscarinic blockade (atropine 5 X 10(-5) mol/L) produces a relaxatory response in canine saphenous veins contracted with prostaglandin F2 alpha. This relaxatory response was shown previously to be resistant to tetrodotoxin. Transmural nerve stimulation (10 V, 1.0 ms) was applied as intermittent trains of stimuli of 30 s duration at frequencies of 1-32 Hz. The veins showed a frequency dependent relaxation (maximum 2.65 +/- 0.20 g). The stimulations were repeated in the presence of lignocaine (10(-3) mol/L), apamin (10(-8) mol/L), ascorbic acid (10(-4) mol/L), or catalase (50 micrograms/mL). The relaxatory response was unaffected by apamin, scorpion toxin, superoxide dismutase, ascorbic acid, and catalase (p greater than 0.05). However, lignocaine (10(-3) mol/L) reduced significantly the relaxatory response to transmural nerve stimulation in this preparation (p less than 0.05). In a separate group of veins, lignocaine (10(-3) mol/L)l abolished the contractile response to transmural nerve stimulation with little effect upon the contractile response to exogenous noradrenaline and the relaxatory responses to isoprenaline and sodium nitrite. These findings support the proposition that the nonadrenergic, noncholinergic tetrodotoxin-resistant relaxatory response observed with transmural nerve stimulation in the canine saphenous vein is mediated by a neural mechanism.

The value of sum of ST segment depression in 12-lead electrocardiogram in relation to change in heart rate during exercise to predict the extent of coronary artery disease.

The present study was planned to investigate whether the sum of ST segment depression in 12-lead electrocardiogram (sigma STD) in relation to change in heart rate (delta HR) during exercise, sigma STD/delta HR index, could be utilized to predict the extent of underlying coronary artery disease. Two hundred and twenty-six consecutive patients were included in this study, 191 men and 35 women, aged 28-74 years (mean 56). Patients were classified into two groups. Group I consisted of 165 patients with either no coronary disease, single or double vessel disease. Group II included 61 patients with triple vessel or left main stem stenosis. It was found that the sigma STD/delta HR index at 25 mm. beat-1 X min. 10(2) provided the best separation between Groups I and II patients. All but 3 of the 61 patients in Group II had a sigma STD/delta HR index greater than 25. In contrast, all but 4 of the 165 patients in Group I had an index less than 25. The sensitivity, specificity and positive predictive value in the identification of Group II patients by using the index were 95%, 98% and 94% respectively. Utilization of ST segment depression of greater than or equal to 2 mm in a VF alone as a test criterion for the recognition of Group II patients had a low sensitivity (41%), specificity (88%) and positive predictive value (56%).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of coronary events following myocardial infarction using a discriminant function analysis.

This study was undertaken to derive an index for predicting coronary events in the first year after a myocardial infarction in "low-risk" patients enrolling in a Cardiac Rehabilitation Program. Data from 145 consecutive patients were analysed. The events were classified as follows: angina requiring further therapy, re-infarction and coronary death. Seventy patients had events: Angina--52, Re-infarction--8, Coronary Death--10. A discriminant function analysis was performed to predict such events using data available at the time of discharge from hospital. The following were significant predictors: (1) previous infarction/angina, (2) radiological evidence of cardiomegaly or lung congestion in the Coronary Care Unit, (3) Non-Q wave infarction and (4, 5 and 6) angina, atrial arrhythmias and a decrease in R wave amplitude in V5 during a pre-discharge exercise test. The jack-knife method classified correctly 71.2% of those with events and 72.6% of those without events. In patients with discriminant scores greater than +0.2, 82% developed events.

Use of impedance cardiography in evaluating the exercise response of patients with left ventricular dysfunction.

Invasive studies in patients with left ventricular dysfunction show that data at rest (e.g. ejection fraction-EF) are poor predictors of the changes in cardiac output (CO) which occur with exercise. This investigation was undertaken to determine whether impedance cardiography could be used in such patients to assess CO response to exercise. The method was compared with the direct Fick method. Over a range of COs between 4 and 18 min-1 there was no systematic error. Reproducibility for CO over one week was highly significant (r = 0.94; P less than 0.001). Impedance cardiography was incorporated into routine exercise testing on a bicycle ergometer for a group of 15 patients (mean age 53.2 +/- 3.0 yrs, SEM) who had sustained a major myocardial infarct 6 to 12 months previously, (EF 38.1 +/- 3.5%, SEM). CO was measured at the end of each 3-min stage. In eight patients (EF 40.0 +/- 3.4%, SEM) CO response was abnormal with either a decrease or a failure to increase with increasing workloads. Conventional end-points i.e. angina, attainment of 85% of predicted maximum heart rate, abnormal blood pressure response or excessive dyspnoea did not indicate consistently a need to terminate the test. It is suggested that impedance cardiography is a useful non-invasive method of evaluating patients with left ventricular dysfunction.

Cardiac output measured by impedance cardiography during maximal exercise tests.

The overall accuracy of cardiac output measurements made by impedance cardiography during maximum exercise was studied in man. Initially, the systematic error of the technique was assessed over the range 3.5 to 18 litre . min-1 by comparing with simultaneous measurements of cardiac output made using the direct Fick method. No systemic error was demonstrated in 40 estimations made in 20 subjects. The random error was assessed in 4 subjects in a steady state at rest and during exercise at 80 and 130 W and found to be less than 5% in each subject. The reproducibility of maximum exercise response was assessed in six healthy male subjects (age 26.2 +/- 4.4 years, +/- SEM) who underwent maximum exercise tests twice, 1 week apart, on a bicycle ergometer. Simultaneous recordings of cardiac output and oxygen uptake (VO2) at rest and during each 3 min stage of exercise were made. Highly significant correlations were obtained in the stroke volume (r = 0.84, p less than 0.001), cardiac output (r = 0.98, p less than 0.001) and VO2 (r = 0.98, p less than 0.001) between the two tests. Average maximum cardiac output was 27.0 +/- 1.2 litre . min-1 (+/- SEM) and maximum VO2 was 4.4 +/- 0.2 litre . min-1 (+/- SEM). These results show that measurements of cardiac output were reproducible over one week. Impedance cardiography is non-invasive technique which is as accurate as invasive methods and can be used for maximal exercise testing.

Cardiovascular responses to early exercise in inferior wall ST acute myocardial infarction.

The heart rate and blood pressure responses to standardized exercise tests were studied in a group of patients with electrocardiographic evidence of inferior wall acute myocardial infarction (AMI). The tests were done on a bicycle ergometer at 8 to 10 days and 10 to 12 weeks after AMI. At 8 to 10 days after AMI, those with ST AMI (n = 12) had a significantly reduced heart rate response to exercise compared with patients with Q-wave AMI (n = 25). This difference was not evident at 10 to 12 weeks. The systolic blood pressure response in patients with ST AMI was lower than that of Q-wave AMI patients during the first exercise test, although the difference did not attain statistical significance but was significantly lower than the responses of both groups at the second test. The patients with ST AMI had smaller amounts of myocardial damage than those with Q-wave AMI as indicated by plasma creatine kinase values (p less than 0.01). These differences in the heart rate responses appeared to result from the preferential activation of nonmyelinated afferent fibers in the subepicardial region of the inferior wall of the myocardium.