Effect of chronic beta-blockade on the ischaemic myocardium: a comparative study with five drugs

The long-term effects of chronic beta-blockade in the rat myocardium were investigated in terms of responses to ischaemic stress. Clinically relevant and equipotent doses of oxprenolol, propranolol, metoprolol, atenolol, and practolol were administered orally for 12 weeks. Twenty-four hours after the last dose, at a time when plasma drug levels were undetectable, hearts were excised and perfused as isolated preparations. During a 3-h period of low-flow, global ischaemia, the time to electromechanical failure following the onset of ischaemia was significantly increased in hearts from animals treated with drugs possessing intrinsic sympathomimetic activity (ISA). Similarly, with ischaemia-induced lactate and enzyme release, hearts from groups treated with drugs possessing ISA showed an increase in release above that of controls, or of hearts from rats treated with beta-blockers which did not possess ISA. These results suggest that in the isolated, globally ischaemic heart, when exogenous catecholamine drive is absent, long-term beta-blockade cannot exert a protective effect when circulating drug levels are undetectable, and compounds possessing ISA may increase tissue damage as measured by lactate and enzyme leakage.