Effects of prolonged administration of oxprenolol on severity of ischaemic arrhythmias, enzyme leakage, infarct size, and intracellular cardiac muscle action potentials.

We examined the effects of prolonged oral administration of oxprenolol (twice daily for 6 weeks) to male Sprague-Dawley rats. At two times (1 or 16-18 h) after the last oral dose, the rats were anaesthetised and subjected to acute coronary artery ligation, and the severity of the resulting arrhythmias was assessed. Ischaemic damage was measured histochemically (using frozen section analysis by toluidine blue dye in nitrobluetetrazolium ) and by myocardial enzyme release. Cardiac muscle (atria and papillary muscle) was also removed and the transmembrane action potentials recorded using conventional microelectrode techniques. When coronary artery ligation was performed 1 h after the last oral dose (at which time there was evidence of substantial myocardial beta 1-adrenoceptor blockade), there was significant reduction in the severity of early arrhythmias, but no evidence that the severity of ischaemic damage was reduced or that the intracellular cardiac action potentials were modified. No protection was observed when coronary artery ligation was carried out 16 h after the last oral dose of oxprenolol. These results support our previous studies with acutely administered beta-adrenoceptor blocking drugs that myocardial beta-adrenoceptor blockade is the main factor involved in the protection afforded by such drugs against early ischaemic arrhythmias and that other possible effects, such as membrane stabilisation and action potential prolongation, are relatively unimportant in this model.