Abstract
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 recitifier 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 Langendorffperfused rat hearts were recorded during initial perfusion, global or regional ischemia and reperfusion. 10-7M of E4031 administered during the initial perfusion did not prolong the QT interval, but slowed the heart rate (Control: 222, E4031: 183bpm, p<0.05), increased myocardial 45Ca2+ uptake (Control: 2.1, E4031: 2.9μmol/g dwt, p<0.05) and attenuated the loss of intracellular K+ during ischemia (Control: 238, E4031: 248μmol/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: 623sec, 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.(Jpn HeartJ 1998; 39: 183-197)
