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Persistence of improved exercise tolerance and degree of revascularization after coronary bypass surgery. A prospective randomized study.

Exercise tolerance was repeatedly determined over a 2-year period in a series of 100 patients with coronary heart disease randomly allocated for medical therapy and coronary bypass surgery. The surgical group had a consistently better exercise tolerance than the medical group during the whole follow-up. Completeness of the revascularization, assessed by repeated graft and native vessel angiography, resulted in a marked improvement whereas incompletely revascularized patients exhibited only a marginal improvement which, nevertheless, to some degree exceeded the result of medical management alone. It is concluded that coronary bypass surgery and medical therapy, when indicated, result in markedly better exercise tolerance than medical management alone. This improvement persists up two years after the operation and is largely dependent on the completeness of the revascularization.

Adrenergic beta-Antagonists

[Wolff-Parkinson-White syndrome. Correlation between the results of electrophysiological investigation and exercise tolerance testing on the electrical aspect of preexcitation].

Fourteen patients with permanent electrocardiographical features of the Wolff-Parkison-White syndrome in sinus rhythm referred for electrophysiological investigation also underwent maximal exercise tolerance tests. The working hypothesis was that in patients with the Wolff-Parkinson-White syndrome with accessory pathways of longer effective refractory periods than the normal pathway (group I) the delta wave should disappear on exercise, whilst in patients with accessory pathways with shorter refractory periods than the normal pathway (group II) the delta wave should persist. Of the 9 patients in group I,the delta wave regressed in 8 and persisted in 1 patient; of the 5 patients in group II, the delta wave persisted in 4 of them. Three patients had attacks of tachycardia during or just after the exercise tolerance test. These results suggest that the exercise tolerance test may help in the identification of patients with accessory pathways with long refractory periods, less susceptible to rapid ventricular rhythms should atrial fibrillation occur, and therefore with better prognoses.

Adolescent

Effects of cedilanid-D in combination with metoprolol on exercise tolerance and systolic time intervals in angina pectoris.

The interaction between cedilanid-D and metoprolol, a selective beta receptor blocking agent, on exercise tolerance and systolic intervals was studied in 15 patients with angina pectoris. The patients had been treated with metoprolol for several months in a dose of 50 mg, three times daily (one patient received 25 mg three times daily). Each patient participated in two studies separated by at least 1 week. After arriving at the laboratory each received 50 mg of metoprolol orally; thereafter, either cedilanid-D or placebo was infused intravenously in a double-blind study performed in randomized order. When the effect of the drugs was maximal, the systolic intervals and the heart volume were recorded at rest, and the exercise tolerance was tested with a bicycle ergometer. The mean maximal value of plasma concentrations of metoprolol assessed during the study was about 50 ng/ml but the variation among subjects was great (20 to 187 ng/ml). After administration of cedilanid-D there was a shortening of the pre-ejection period and left ventricular ejection time compared with results after placebo; the reduction was similar to that found after administration of cedilanid-D without beta blocking drugs. The total heart volume decreased by an average of 55 ml, but the individual variation was great. The patients' average work capacity, expressed as total work, was not altered by cedilanid-D when compared with results after placebo. No relation was found between initial heart size and the effect of cedilanid-D on capacity for physical work. It therefore appears that there is no indication for the routine use of digitalis during beta blocking therapy in patients with angina pectoris who do not have cardiac failure.

Adrenergic beta-Antagonists

The effect of aerosol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis.

In a double-blind placebo controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, ipratropium bromide 40 microgram and salbutamol 200 microgram produced similar and significant (P less than 0.001) increases in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A greater increase in FEV1 and FVC was seen when both drugs were used together, but this increase did not differ significantly from that produced by either drug alone. Salbutamol increased 12-minute walking distance significantly (P less than 0.001) by 62 +/- 15 metres, whereas the increase of 43 +/- 15 metres observed after ipratropium was not significant (P less than 0.05). With both drugs in combination 12-minute walking distance increased by 72 +/- 15 metres, but this change was not significantly different from that observed with salbutamol alone. If aerosol bronchodilators in the doses used in this study are to be given with a view to improving exercise tolerance in such patients than salbutamol would appear to be the aerosol of choice.

Aerosols

Acebultolol: basis for the prediction of effect on exercise tolerance.

Twelve unselected males suffering from documented coronary insufficiency and moderately severe angina submitted to graded multistage treadmill exercise testing on 3 separate days, 3.5 hr after a single dose of 0,200, or 400 mg of acebulolol, a cardioselective beta blocker. Control measures included random allocation of 2 patients to each of 6 balanced sequences of administration, standardized double-blind conditions, and variance analysis for Latin-square design with repeated measures on each subject. Performance was evaluated by measuring time elapsed until anginal pain, peak heart rate, peak product of heart rate and blood pressure, and peak oxygen consumption. Mean values for all criteria were significantly atered by 400 mg of acebutolol. Seven out of twelve patients were classified as responders (i.e., exercise duration increased 100% or more). The response after acebutolol was correlated with the performance on placebo in the base of exercise duration, peak heart rate, and peak product of heart rate and blood pressure. It is concluded that: (1) performance criteria are useful predictors of response to beta blockade and (2) acebutolol is a potent antianginal agent when judged by an objective treadmill exercise test.

Acebutolol

The effect of beta-adrenoceptor blockade on factors affecting exercise tolerance in normal man.

1 We have studied the effects of single oral doses of 80 mg propranolol and 100 mg metoprolol on the cardiovascular and respiratory responses to progressive exercise in nine healthy men in double-blind, placebo-controlled experiment. As judged by their effects on exercise heart rate and cardiac output the doses of the two drugs used were equivalent. 2 Beta-adrenoceptor blockade reduced oxygen consumption by 3.5% over the whole work range with an increase in the respiratory exchange ratio of 0.056 units. Carbon dioxide production and exercise ventilation were unchanged. The two drugs had similar effects. Possible mechanisms for these observations are discussed. 3 Perceived exertion during exercise was increased by both the beta-adrenoceptor blocking drugs and this may be of relevance to the symptom of fatigue reported by patients on these drugs. Endurance, assessed as either total work done or maximal work achieved, was reduced by 15%.

Adrenergic beta-Antagonists

Increased exercise tolerance with nitrates in beta-blockaded patients with angina.

In 14 beta-blockaded anginal subjects, 10 of whom had poor left ventricular function, sublingual isosorbide dinitrate significantly increased maximal exercise capacity on a standardized multistage treadmill test. This was associated with changes in heart rate and blood pressure suggestive of a fall in left ventricular work. The effect of isosorbide lasts for at least two hours and when taken before exercise may be a useful addition to beta-blockade in patients with angina.

Adrenergic beta-Antagonists

Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.

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.

Adult

[Correlations between effort tolerance and the severity of coronary disease. Influence of myocardial lesions].

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.

Blood Pressure

Angina in hypertensive patients. With particular reference to the negative chronotropic effects of sympatholytic therapy.

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.

Adrenergic beta-Antagonists

[Continuous ambulatory electrocardiographic recordings using the Holter system in the late phase of hospitalization for recent myocardial infarct. Value and limitations studied in a series of 100 patients].

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.

Adrenergic beta-Antagonists

Effects of a new beta1-selective beta-blocker H 87/07 in angina pectoris.

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.

Adrenergic beta-Antagonists

Effects of the cardioselective beta-adrenergic receptor blocking agent metoprolol in angina pectoris. Subacute study with exercise tests.

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.

Adrenergic beta-Antagonists