Abrupt propranolol withdrawal in angina pectoris: effects on platelet aggregation and exercise tolerance.
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Most authors agree that physical training in a cool environment improves tolerance to exercise in the heat and the rate of heat acclimatization, but the extent or degree of improvement remains controversial. The best improvement in heat tolerance for men is associated with intensive interval or continuous training at a training intensity greater than 50% of maximal oxygen uptake (Vo2max) for 8-12 weeks; the Vo2max should be increased 15-20%. Far less is known about the appropriate type, intensity and duration of endurance training associated with improved exercise-heat tolerance in women. The major benefits of physical training appear to apply to both short term (less than 2 hrs) or long term (greater than 2 hrs) exercise-heat exposures for men. Generally, individuals with high Vo2max values (previously trained and endurance athletes) are at an advantage in the heat. Utilization of proper physical training appears to produce about 50% of the total adjustment resulting from heat acclimatization, while increased fitness is associated with greater retention of acclimatization in cool environments. Female athletes appear somewhat better able to tolerate exercise in hot environments than nonathletic females while differences between highly trained females and males do not appear as dramatic as once thought.
A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.
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Although ventricular tachycardia is a well-known complication of myocardial ischaemia and may be provoked by exercise, many patients may appreciate only the angina and be unaware of the unduly rapid heart rate that precipitates it. Exercise testing is needed to show this arrhythmia and to enable treatment to be started.Twenty-three patients were found to have chronic ischaemic heart disease complicated by ventricular tachycardia. Six patients with old myocardial infarction had ventricular tachycardia at rest which required conversion to sinus rhythm; 17 patients developed ventricular tachycardia only when they exercised. In 12 of these 17 patients coronary angiography showed disease of the anterior descending branch of the left coronary artery; other vessels were usually also affected. Although beta-adrenergic blocking drugs increased exercise tolerance, ventricular tachycardia still occurred when the heart rate on exercise reached a level similar to that before treatment. In five patients coronary artery bypass surgery was performed because of angina and exercise-induced ventricular tachycardia. Exercise tolerance was increased in all three patients who underwent exercise tests after operation, and in two of these patients, both of whom were known to have patent grafts, ventricular tachycardia was abolished.If part of the beneficial effect of coronary bypass surgery is preventing life-threatening ventricular arrhythmias it is essential to detect these, and ambulatory monitoring and stress testing have a complementary role.
The influence of coronary and myocardial lesions, defining the severity of the coronary artery disease on effort tolerance was studied in 51 patients. The appearances of the coronary arteriography and ventriculography were compared with the parameters of exercise tolerance: electrocardiographic changes, maximal charge (Cw), total work (TW), maximal systolic arterial pressure (SAP), maximal heart rate, percentage of the theoretical maximal heart rate, double product, exercise capacity index (CEI). The results showed that exercise tolerance (Cw, TW, ECI) and the exercise SAP are mainly affected by the myocardial lesions: patients with very reduced left ventricular ejection fractions and double or triple artery disease have very low indices: average Cw of 60 watts, TW less than 20,000 joules, ECI approximately 50. The SAP only rises slightly. On the other hand, patients with normal or subnormal ejection fractions have much higher indices whatever the state of their coronary arteries; Cw over 80 watts, TW over 30,000 joules, ECI over 80. In addition, major left ventricular dysfunction is associated with ST segment elevation during exercise.
In 222 patients with coronary heart disease hemodynamics at rest and during exercise were measured before and after aortocoronary bypass surgery. A total of 552 grafts were constructed, i.e. an average of 2.47 grafts per patient. Only 10.8% of the patients had a 1-vessel-disease, 59.2% had a 3-vessel-disease. 10.8% of the patients were provided with one graft, 49.7% got 3 or 4 grafts. In 92.8% of the patients the r. desc. ant. was significantly stenosed, and in 94.2% this vessel has been provided with a graft. Preoperatively only 7 patients had no angina pectoris during exercise (bicycle ergometer in supine position, each load lasting 6 min), postoperatively 154 patients have been completely free of angina pectoris. The preoperative angina pectoris-free exercise tolerance was 27.4 +/- 27.4 W (means +/- SD), postoperatively it was 76.5 +/- 33.8 W. The largest increase of exercise tolerance was observed in patients with a 3-vessel-disease (208%). Preoperatively only 10.1% had normal values of pulmonary wedge pressure and cardiac output at rest and during exercise, postooperatively 51.5%. The postoperative normalization of hemodynamics depends on the number of vessels involved (1-vessel-disease 86%, 3-vessel-disease 39.8% normalization) and on the status of the left ventricle (without a previous transmural myocardial infarction 68.4%; with a previous myocardial infarction 41.0%). The effects of revascularization on myocardial ischemia can be evaluated by measurements of pulmonary wedge pressure and cardiac output at rest and during exercise.
There was no significant difference in the blood pressure and heart rate response of hypertensive patients with and without angina to standardised exercise on a treadmill before and after anti-hypertensive treatment. There was no improvement in exercise tolerance in the hypertensive patients with angina treated with bethanidine, debrisoquine or guanethidine despite a reduction of resting and exercise heart rates after treatment. The negative chronotropic effect of these sympatholytic drugs was less than that of oxprenolol or propranolol, but the hypotensive response was greater. Both of these beta-receptor blocking drug produced an an improvement in exercise tolerance in patients with angina either alone or in combination with other hypotensive therapy. The best control of blood pressure and angina was often achieved by a combination of a sympatholytic drug and beta-receptor blocking drug. In hypertensive patients treated for several years, angina at presentation was occassionally reduced by reduction of blood pressure. Later onset of angina appeared to be unrelated to control of hypertension but to be due to coincidental coronary occlusion. There was no evidence that myocardial infarction was precipitated by postural or exercise hypotension although these effects occasionally precipitated angina.
Repeated continuous ambulatory electrocardiography by Holter monitoring was performed after early mobilisation post-myocardial infarction in 100 patients, without ventricular extrasystoles on classical ECG. Frequent ventricular arrhythmias were recorded in 58 p. 100 cases, unrelated to the localisation of the infarct. The observation of ventricular arrhythmias in the Coronary Care Unit (CCU) was not related to the occurrence of VEs during Holter monitoring. On the other hand, VEs were less frequent (38 p. 100 compared to 68 p. 100) in patients taking amiodarone or betablockers on transfer from the CCU. The reduced activity of patients during Holter monitoring minimises the frequency of arrhythmias, and 10 p. 100 patients were observed to have VEs only after exercise tolerance testing. These VEs seem to be a bad prognostic factor; the 9 patients who died in this series all presented VEs on ambulatory monitoring (7) or during exercise tolerance testing (2). However the number of patients with triple vessel disease was greater in the group with VEs on ambulatory monitoring (57 p. 100 compared with 13 p. 100). It is difficult to assess the precise role of the VEs amongst the other risk factors of sudden death. This is not a randomised study, but it would appear that long=term amiodarone or betablockers therapy may influence the medium-term prognosis.
The effects of glucose-insulin-potassium (GIK) and placebo normal saline (S) infusion on treadmill-walking time to angina, ST depression, heart rate (HR), systolic blood pressure (SBP), rate pressure product (RPP), blood glucose (G), lactate (L) and free fatty acids (FFA) were studied in 14 non diabetic patients with exertional angina. For the whole group, the post-GIK walking time to angina (393 +/- 33 sec, mean +/- SEM) was greater than the values during control GIK (319 +/- 20 sec, p less than 0.02) and post-S infusion (334 +/- sec, p less than 0.05), but circulatory and ST responses were similar in post-GIK and post-S studies. 7 of the 14 patients experienced significantly greater improvement in exercise tolerance following GIK (467 +/- 39 sec) in comparison to control GIK (313 +/- 29 sec, p less than 0.001) and post-S infusion (334 +/- 32 sec, p less than 0.005) and exercised to a higher HR, SBP and RPP after GIK than after S infusion. At the onset of angina these patients had similar ST-segment depression before and after GIK but when ST segments were assessed after GIK at the same exercise duration when angina had occurred during the control and post-S studies, there was significantly less ST depression (p less than 0.01). Of the remaining 7 patients exercise tolerance following GIK deteriorated in 3, remained unchanged in 2 and increased by 12 and 48 sec in 2 patients in comparison to post-S values. Comparison of post-GUK and post-S values for G, L and FFA for the whole group showed significantly lower resting values of FFA and post-exercise values of G following GIK infusion. The differences in clinical and circulatory responses between patients who improved and those who did not improve following GIK were not related to the angiographically determined severity of coronary artery disease or to GIK-induced metabolic changes. Results suggest that some patients with angina pectoris do benefit from GIK infusion but the response in a given patient to this therapeutic modality is unpredictable.
Changes in myocardial perfusion and left ventricular function were evaluated pre- and post-operatively (3--6 months) in 14 patients with unstable angina who underwent coronary artery bypass surgery. Perfusion was studied with intracoronary and intragraft injections of radiolabeled macroaggregated albumin particles. Of 20 abnormal perfusion areas identified preoperatively, 13 demonstrated improved perfusion post-operatively. Segmental analysis of the left ventriculogram demonstrated improved wall motion in 29 abnormally contracting segments; 18 normalized. Areas which showed improvement of left ventricular perfusion were invariably associated with improvement of left ventricular wall motion. Five patients showed improvement in perfusion and contraction in areas of apparent old myocardial infarction. Thirteen of the 14 patients had significantly less angina whether or not there was evidence of improved perfusion. However, only those patients who demonstrated improved perfusion had a significant improvement in their treadmill exercise tolerance postoperatively. Thus, patients with unstable angina have perfusion defects which may be reversed as a result of saphenous vein graft surgery. Reversal of these perfusion abnormalities results in improved left ventricular performance and better exercise tolerance postoperatively.
The efficacy and toleration of a new beta1-selective beta-blocker, H 87/07, was compared with placebo in 33 patients with angina pectoris. The efficacy was evaluated using subjective assessments of attack rate and nitroglycerin consumption as well as objective assessments of exercise tolerance on a bicycle ergometer. H 87/07 significantly reduced the attack rate and the nitroglycerin consumption compared with placebo. The mean reduction amounted to 13 and 36% respectively. No significant differences were found between H 87/07 and placebo with regard to exercise tolerance. Due to high intrinsic stimulating activity (I.S.A.) H 87/07 altered the heart rate and blood pressure only slightly at rest but during exercise significant reductions were seen. Except for one patient who had cardiac decompensation on H 87/07 no side-effects of clinical importance were seen. No significant changes were seen with regard to the laboratory tests performed.
Mood and physical performance were assessed in medically and surgically treated patients with coronary artery disease referred to a cardiovascular rehabilitation program early in convalescence. Surgically treated patients reported less mood disturbance prior to training and demonstrated greater gains in exercise tolerance. Medically managed patients had more mood disturbance prior to training and greater mood improvement in the six week rehabilitation program. Improvements in mood were independent of improvement in exercise tolerance. Group differences in mood state could not be attributed to the use of defensive denial, time from discharge, severity of coronary disease, or age of patient. The psychological and physical impact of bypass surgery contributes to the mood and physical performance of postoperative patients.
Twenty-one patients, mean age 60.3 years, with stable angina pectoris earlier treated with beta-blockers, were investigated with standardized exercise tests to evaluate the action of nifedipine alone and in combination with a beta-blocker. The first exercise test was performed 3 weeks after treatment with the patient's usual beta-blocker. Following this, the patients were tested twice after a double-blind cross-over 3-week trial with nifedipine and placebo. The patients were subsequently treated for 3 weeks with nifedipine 10 mg 3 times daily or placebo and then performed an exercise test. During the 4th period of 3 weeks the patients took a combination of nifedipine, 10 mg 3 times daily, and their usual beta-blocker and then performed the final exercise test. Nifedipine alone raised the heart rate by 5 beats/min at rest and diminished the systolic blood pressure at rest by 17 mm Hg. During exercise at comparable load the heart rate did not change significantly, but the systolic blood pressure decreased with 22 mm Hg. The exercise tolerance expressed as total work increased on a average by 20%, range-14 - + 194%. Nifedipine in combination with a beta-blocker gave a further decrease in the systolic blood pressure, totally 37 mm Hg at comparable load. The exercise tolerance increased more, totally by an average of 41%. There was a significant correlation between basal values for systolic blood pressure registered during the placebo period at rest and the percentage change in total work. The atrioventricular conduction time did not change significantly compared to placebo during treatment with nifedipine or the combination nifedipine + beta-blocker. No serious side-effects were observed during the study.
The effect of a cardioselective beta-adrenergic blocking agent, metoprolol, on symptoms and exercise tolerance was studied in 16 patients with angina pectoris. Metroprolol was compared with placebo at two dose levels (20 mg t.d.s. and 50 mg t.d.s.) in a double-blind trial in 14 patients. Compared with placebo, metroprolol caused a significant reduction of heart rate and systolic blood pressure during exercise, and consequently a reduction of the rate-pressure product. The reduction was greater with 50 mg t.d.s. than with 20 mg t.d.s. The exercise tolerance measured as total work increased significantly by 21 per cent during treatment with metroprolol 20 mg t.d.s., and by 17 per cent during treatment with 50 mg t.d.s. There was a reduction in the number of anginal attacks and in nitroglycerin consumption, and subjective improvement of angina pectoris at both dose levels of metroprolol. No signs of cardiac failure appeared during any of the four treatment periods. Heart volume showed no significant change. Unwanted effects were of the same frequency and severity during treatment with metroprolol at both dose levels as with placebo.