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In this study we have assessed the possibility that long-term beta-blockade may offer additional protection against myocardial ischaemia that is separate from that afforded by acute beta-blockade. In addition, the effect of intrinsic sympathomimetic activity (ISA) on this additional protection was also investigated. Equipotent doses (4 mg . kg-1 body wt . day-1) of oxprenolol (possessing ISA) or propranolol (without ISA) were administered orally to rats for 3 weeks. Hearts were excised an perfused as isolated "working" heart preparations at variable times after the last dose. Hearts excised on the final day of drug administration showed significantly higher basal functional performance compared with untreated hearts. After 30 min reduced flow ischaemia (in the presence of exogenous catecholamine drive) hearts were aerobically reperfused and functional recovery measured. In both chronically beta-blocked groups, at times when plasma drug levels were undetectable, the number of hearts that recovered function and the cellular levels of creatine phosphate and glycogen were significantly increased. In addition, hearts from the oxprenolol-treated group perfused on the final day of drug administration, exhibited a greater recovery of heart rate compared with both propranolol treated and untreated groups. These results indicate that secondary consequences of long-term beta-blockade are beneficial to the ischaemic myocardium in the presence of high catecholamine drive. In addition, the possession of ISA by oxprenolol offered some advantages in terms of post-ischaemic functional recovery.

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