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

Abstract

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 doubleblind, 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 fp-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 f-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%.One of the main therapeutic uses of f-adrenergic receptor blocking drugs has been in the management of angina pectoris. Many authors have reported improved exercise tolerance in these patients with delayed onset of both ischaemic pain and ECG abnormalities and reduced dependence on coronary vasodilators- (Comerford & Besterman, 1976). 0-adrenoceptor blocking drugs are also widely used in the control of hypertension, often in patients whose exercise tolerance is presumably normal. As adrenergic mechanisms play a major role in facilitating oxygen transport through their involvement in the control of cardiovascular and respiratory adjustments during exercise, it is important to establish the effect of f-adrenoceptor blockade on exercise tolerance, particularly as there is now evidence that the cardiovascular reserves of untrained but otherwise healthy people are more limited than generaly appreciated (Wasserman, Whipp, Koyal & Beaver, 1973). Using normal individuals we have measured cardio-respiratory variables and the level ofperceived exertion during a standard progressive exercise test. Nine subjects were exercised to exhaustion while taking either metoprolol, propranolol or placebo. In this way the effects of both non-selective and more cardio-selective ,B-adrenergic receptor blockade have been studied. MethedsNine healthy adult male volunteers with normal lung function were used as subjects. They were aged 25 to 42 years (mean + s.d. 35 + 7 years), and gave their informed consent to a protocol which had been approved by the Ethical Committee of the Department of Physiology and Pharmacology.Identical tablets containing either 80 mg propranolol (Inderal, ICI) or 100 mg metoprolol (Betaloc, Astra) or lactose were used, and neither the subjects nor the experimenters were aware of the code used to identify the tablets. Three experiments were performed on each subject and at least 48 h elapsed between experiments on any individual. The order of the drugs was randomized between individuals to reduce bias due to any training effect of the procedure. Each experiment took 1.5 h and it started

The effect of acute vs chronic treatment with P–adrenoceptor blockade on exercise performance, haemodynamic and metabolic parameters in healthy men and women

“…Previous studies have reported conflicting results regarding the effect of P-adrenoceptor blockade on Vo, during submaximal exercise, as both a reduction [ 3,131 and no effect have been found [2, metabolic adaption may also explain our finding of reduced plasma lactate concentrations after chronic propranolol treatment. Such an adaption also appears to take place in the ischaemic myocardium where the administration of propranolol causes reduced myocardial oxygen requirement and a shift in substrate utilization with improvement of lactate metabolism from substantial production to extraction [45].…”

The effect of a week's beta‐adrenoceptor antagonism on daytime heart‐ rates, subjective responses to exercise, and physical activity in normal subjects.

“…The effects of the P-adrenoceptor antagonists on the heart rate response to progressive ergometer exercise are entirely consistent with previous studies (Anderson et al, 1979;Pearson et al, 1979;Wilcox et al, 1984 Lxolol. rate during the day or over 24 h (Carrageta et al, 1982;Floras et al, 1982;Rowlands et al, 1982).…”

Effects of beta‐adrenoceptor blockade on exercise performance and respiratory response in healthy, physically untrained humans.

“…In fact, similar studies did not always show consistent results. For instance, all studies performed on healthy subjects who were able to reach high work rates (usually more than 200 W) showed a reduction of oxygen uptake and maximum work capacity after 3-adrenoceptor blockade (Pearson et al, 1979;Anderson et al, 1979;Twentyman et al, 1981;Tesch & Kaiser, 1983;Petersen et al, 1983), whereas no changes were found in studies carried out in subjects unable to reach such work levels, either healthy (Leitch et al, 1980) or suffering from mild hypertension (Fagard et al, 1980).…”