The deleterious effects of myocardial catecholamines on cellular electrophsiology and arrhythmias during ischaemia and reperfusion

Abstract

Action potentials and ECGs were recorded from Langendorff perfused guinea pig hearts during ischaemia and reperfusion. Arrhythmias were significantly more frequent during low flow (10% of control) than zero flow ischaemia and were most frequent during reperfusion following 30 minute ischaemia. Arrhythmias during low flow ischaemia were preceded by spontaneous recovery in action potential amplitude and Vmax and marked shortening of refractory period which did not occur during zero flow ischaemia. Reperfusion VF was always preceded by further shortening of the action potential. Myocardial catecholamine depletion, by pre-treatment with 6-hydroxydopamine significantly reduced the incidence of arrhythmias during ischaemia and reperfusion. Catecholamine depletion blunted the ischaemia-induced reduction in action potential amplitude and Vmax, prevented any spontaneous recovery and abolished reperfusion induced shortening of action potential duration. Methoxamine given to catecholamine-depleted hearts, having only minor effects during normal perfusion, significantly reversed the anti-arrhythmic and electrophysiological effects of catecholamine depletion during ischaemia and reperfusion. Phentolamine and propranolol in anti-arrhythmic concentrations, profoundly modified the electrophysiological effects of ischaemia and reperfusion. These results suggest that release of endogenous myocardial catecholamines contributes through alpha and beta-adrenoceptor stimulation to the electrophysiological changes and arrhythmias during myocardial ischaemia and reperfusion.