REVERSIBILITY OF ELECTROPHYSIOLOGIC ABNORMALITIES OF SUBENDOCARDIAL PURKINJE-FIBERS INDUCED BY ISCHEMIA

Introduction: During the subacute phase of infarction in the canine he art, the subendocardial Purkinje fibers subtended by the infarct show depolarization greater than can be accounted for by the decrease in [K +](i), and generate abnormal action potentials and spontaneous rhythms due to abnormal automaticity. We have used pinacidil to hyperpolarize these fibers and evaluate the extent to which an increase in resting potential can normalize action potential generation. Methods and Resul ts: Twenty-four hours after two-stage ligation of the canine left ante rior descending coronary artery, preparations of subendocardial Purkin je fibers were studied in vitro by recording transmembrane potentials through standard microelectrodes and exposing the preparation to pinac idil and increases in [K+](o). Pinacidil increased resting potential t o the estimated value of E(K), abolished the abnormal automaticity, an d restored action potentials of normal amplitude with normal values of V-max. This effect often persisted after washout of pinacidil. Elevat ion of [K+](o) from 4.0 to 20.0 mM slightly increased maximum diastoli c potential, suggesting that the excess (over the change in E(K)) depo larization was caused by a decrease in g(K1). Conclusion: The ventricu lar arrhythmias seen during the subacute stage of infarction probably are caused by abnormal automaticity. Our findings support the conclusi on that this abnormal automaticity arises in partially depolarized sub endocardial Purkinje fibers. This loss of resting potential is due in large part to a decrease in g(K1). Restoration of resting potential to the value of E(K) permits the Purkinje fibers to develop essentially normal action potentials. An agent capable of reversing the partial bl ock of I-K,I-1 thus might be an effective drug for some types of arrhy thmias.