Concentration- and rate-dependent electrophysiological effects of restacorin on isolated canine purkinje fibres

Andràs Varrò, Timothy K. Knilans, Péter P. Nànàsi, György Rabloczkys, David A. Lathrop

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The cellular electrophysiological effects of restacorin, a new antiarrhythmic agent were studied using conventional microelectrode techniques in isolated dog cardiac Purkinje fibres. Restacorin (1 - 30 μmol/l) decreased the maximum rate of rise of the action potential upstroke and action potential amplitude while action potential duration measured at 90% of repolarization was shortened in a concentration-dependent manner during pacing at a constant basic cycle length of 500 ms. The effect of 10 μmol/l restacorin on maximal rate of rise of the action potential upstroke and on action potential duration measured at 90% of repolarization were also studied while varying the constant pacing cycle length between 300 and 5000 ms. The results of these studies indicated a rate-dependent effect of restacorin on the action potential characteristics examined. After abrupt changes in cycle length, 10 μmol/l restacorin slowed the fast component of the relation for restitution of action potential duration from 155.3 ± 5.2 ms (control, n = 6) to 217.1 ± 17.8 ms (n = 6, P < 0.05). In the presence of restacorin (10 μmol/l), a second slow component for recovery of maximal action potential up stroke rising velocity was expressed having a time constants of 8.5 ± 1.2 s. The range of premature action potential durations was significantly decreased (by 57.1%, P < 0.01) by 10 μmol/l restacorin. These results indicate that the cellular electrophysiological effects produced by restacorin in dog cardiac Purkinje fibres best resemble those produced by recognized class Ic antiarrhythmic drugs.

Original languageEnglish
Pages (from-to)691-697
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume342
Issue number6
DOIs
Publication statusPublished - Dec 1 1990

Keywords

  • APD restitution
  • Antiarrhythmic drugs
  • Electrophysiology
  • Recovery of {Mathematical expression}
  • Restacorin

ASJC Scopus subject areas

  • Pharmacology

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