Arrhythmogenic and electrophysiological effects of alpha adrenoceptor stimulation during myocardial ischaemia and reperfusion

Abstract

To examine possible arrhythmogenic effects of alpha adrenoceptor stimulation, we studied the effects of methoxamine 10(-6) M on arrhythmias and cellular electrophysiology during global myocardial ischaemia and reperfusion in isolated Langendorff perfused guinea-pig hearts. To avoid interference from release of endogenous catecholamines during ischaemia or reperfusion, experiments were performed using catecholamine depleted hearts (myocardial noradrenaline = 11% of control). Catecholamine depletion markedly reduced the incidence of VT and VF during ischaemia and reperfusion and perfusion with methoxamine significantly reversed this. This arrhythmogenic effect of methoxamine was only observed during ischaemia or reperfusion, was independent of beta adrenoceptor blockade and H2 receptor blockade but was abolished by alpha adrenoceptor blockade with phentolamine. Catecholamine depletion blunted the ischaemia induced fall in action potential amplitude and Vmax and prolonged action potential duration and refractory period. Perfusion with methoxamine either partially or completely reversed these effects. Thus, alpha adrenoceptor stimulation has little effect on normally perfused myocardium, but may induce VT or VF during ischaemia or reperfusion.