Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts.

Abstract

UNLABELLED The delayed outward rectifier K+ channel has a role in the increase in automaticity of myocytes under pathophysiological conditions. The purpose of the present study was to clarify the effect of blockade of outward rectifier K+ channels by a class III antiarrhythmic drug, E4031, on ischemia- and reperfusion-induced arrhythmias. Ion fluxes, energy metabolites and cardiac function were measured and the epicardial electrocardiograms of Langendorff-perfused rat hearts were recorded during initial perfusion, global or regional ischemia and reperfusion. 10(-7) M of E4031 administered during the initial perfusion did not prolong the QT interval, but slowed the heart rate ( CONTROL 222, E4031: 183 bpm, p < 0.05), increased myocardial 45Ca2+ uptake ( CONTROL 2.1, E4031: 2.9 mumol/g dwt, p < 0.05) and attenuated the loss of intracellular K+ during ischemia ( CONTROL 238, E4031: 248 mumol/g dwt, p < 0.05). E4031 tended to reduce ischemia-induced ventricular tachyarrhythmias ( CONTROL 60, E4031: 30%, n.s.), but reperfusion-induced ventricular tachyarrhythmias were sustained longer by the administration of E4031 (CONTROL: 255, E4031: 623 sec, p < 0.05). Prior exposure to E4031 decreased the depletion of high energy phosphates during ischemia, but suppressed their recovery during reperfusion. These results suggest that the attenuated loss of K+ from the ischemic myocardium and the decrease in heart rate by E4031 contributed to the reduction of ischemia-induced arrhythmias. However, the increase in myocardial Ca2+ uptake and altered energy metabolism may be responsible for the increase in reperfusion-induced arrhythmias.

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@article{Shinmura1998EffectOE, title={Effect of E4031, a class III antiarrhythmic drug, on ischemia- and reperfusion-induced arrhythmias in isolated rat hearts.}, author={Kazuya Shinmura and Masaji Tani and Hiroshi Hasegawa and Yasuhiro Ebihara and Yuji Nakamura}, journal={Japanese heart journal}, year={1998}, volume={39 2}, pages={183-97} }