Effects of flunarizine on impulse initiation in canine Purkinje fibers

Jeanny K Park, P. Danilo, M. R. Rosen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Introduction: The calcium channel blocker, flunarizine, selectively blocks accumulation of intracellular calcium during conditions of calcium overload. It has been reported to selectively terminate delayed afterdepolarization- induced arrhythmias in intact dogs. Methods and Results: Using standard microelectrode techniques, we studied the effects of flunarizine on the transmembrane action potential and various arrhythmogenic mechanisms in canine Purkinje fibers. Flunarizine significantly decreased the fast response action potential duration at 50% repolarization in a concentration-dependent manner (10-8 to 10-5M), but had no effect on maximum diastolic potential, overshoot, maximum upstroke velocity (V̇(max)), or APD at 90% repolarization. For Ca2+-induced slow response action potentials, flunarizine decreased the overshoot, and prolonged action potential duration at both 50% and 90% repolarization. It had no effect on automaticity of Purkinje fibers exposed to solutions containing either low [K+] or barium chloride. Flunarizine, 10-5M, inhibited the development of both ouabain- induced and calcium- and catecholamine-induced delayed afterdepolarizations. It did not inhibit the development of cesium-induced early afterdepolarizations. Conclusions: Thus, in vitro, flunarizine selectively suppresses delayed afterdepolarizations and has no effects on early afterdepolarizations or normal or abnormal automaticity. Hence, its utility in intact animal models of triggered arrhythmias is borne out mechanistically in these isolated tissue studies.

Original languageEnglish (US)
Pages (from-to)306-314
Number of pages9
JournalJournal of Cardiovascular Electrophysiology
Volume3
Issue number4
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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