Effects of clofilium on ischemic subendocardial Purkinje fibers 1 day postinfarction

Abstract

One day after ligation of the canine anterior descending coronary artery, clofilium, a long-acting class III anti-arrhythmic agent, was studied for its effects on normal and ischemic Purkinje fibers. In normal Tyrode's solution (4 mMpotassium, 2.7 mMcalcium) clofilium (10−7to 10−5M) increased action potential duration. Although only 2 of 10 normal Purkinje fibers developed early afterdepolarizations and early afterdepolarization-initiated triggered activity, 10 of 11 ischemic Purkinje fibers developed these features. Consequently, action potentials in ischemic fibers were prolonged to durations >10 s. The triggered activity in the ischemic Purkinje fibers produced repetitive activity in adjacent normal ventricular muscle.In vivo, 3 days after ligation, the administration of 3 to 10 mg/kg clofilium induced grouped beating. Action potentials recorded subsequently from these same hearts in vitro showed early afterdepolarizations, triggered activity and a similar grouping of responses. Therefore, clofilium differentially produced early afterdepolarizations in ischemic Purkinje fibers. This is a mechanism by which clofilium could be arrhythmogenic in an ischemic heart.