The influence of clinical doses of drugs that affect beta-adrenoceptors has been examined on heart rate, blood pressure, duration of exercise, and on electrolyte concentrations (Na, K, Ca and Mg) during recovery from exercise in healthy volunteers. The drugs used were a beta 1-adrenoceptor antagonist atenolol, a nonselective beta-adrenoceptor antagonist propranolol, and a cardioselective, partial beta 1-adrenoceptor agonist with 43% ISA activity, xamoterol. The duration of exercise was smaller on propranolol. Maximum exercise heart rate and blood pressure were reduced significantly by propranolol and atenolol. Xamoterol reduced maximum exercise heart rate and had no effect on blood pressure. The degree of breathlessness and fatigue revealed no differences between treatments. Recent evidence has suggested an association between hyperkalaemia and hypomagnesaemia with an increase in the occurrence of arrythmias following acute myocardial infarction. Exercise-induced hyperkalaemia has been suggested as a factor in sudden death. The results confirmed a rise in serum potassium during exercise and attenuation of the fall during recovery under beta-adrenoceptor blockade. Xamoterol was no different from placebo in these respects. Exercise also produced a rise in magnesium levels and during recovery the level fell below baseline. Both these effects were attenuated by propranolol. Calcium levels were not affected by any of the treatments.
This study was designed to assess the efficacy of xamoterol in 14 patients with mild to moderate heart failure over a period of 18 months. A beneficial effect on exercise capacity and a lowering of heart rate on exercise was sustained, and ejection fraction did not change, although some deterioration may be expected over this length of time in patients with heart failure. Xamoterol is safe and effective, and its benefits are maintained over at least 18 months.
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