Effects of clofilium on ischemic subendocardial Purkinje fibers 1 day postinfarction.

One day after ligation of the canine anterior descending coronary artery, clofilium, a long-acting class III antiarrhythmic agent, was studied for its effects on normal and ischemic Purkinje fibers. In normal Tyrode's solution (4 mM potassium, 2.7 mM calcium) clofilium (10(-7) to 10(-5) M) increased action potential duration. Although only 2 of 10 normal Purkinje fibers developed early after depolarizations 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 greater than 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.