Electrophysiologic effects of FPL 13210 on canine Purkinje fiber action potential duration and Vmax comparison to disopyramide

T. K. Knilans, A. Varró, P. P. Nánási, R. J. Murray, F. C. Kaiser, D. A. Lathrop

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The frequency-dependent effects of FPL 13210, a new disopyramide derivative, were examined in isolated canine cardiac Purkinje fibers paced at a frequency of 2 Hz and following abrupt changes in pacing cycle length. At 2 Hz, FPL 13210 depressed Vmax while shortening action potential duration measured at 50% of repolarization (APD50) and not affecting duration measured at 90% of repolarization (APD90). These effects were concentration dependent over the range of 1-30 μM. The depression of Vmax produced by 5μM FPL 13210 was not significantly different than that produced by 18 μM disopyramide while the preparations were paced constantly at 2 Hz. At these concentrations, recovery of Vmax was slowed by both FPL 13210 and disopyramide. The slow time constant estimated for this relation after exposure to FPL 13210 was approximately 6.5 times longer than that estimated following administration of disopyramide. In addition, APD90s evoked by early premature stimuli in the presence of 5 μM FPL 13210 were longer than those produced in the absence of drug when the diastolic interval was less than 60 ms. Later extra stimuli evoked at diastolic intervals longer than 100 ms produced shorter APD90s after FPL 13210 administration. Therefore, when FPL 13210 is compared to disopyramide using concentrations selected to produce equivalent degrees of Vmax depression, FPL 13210 produced effects on APD90 that were opposite to those produced by disopyramide when the diastolic interval was longer than normal. These effects of FPL 13210 would suggest that this compound should be classified as a class Ic antiarrhythmic agent, unlike disopyramide, a class Ia antiarrhythmic agent.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume5
Issue number1
DOIs
Publication statusPublished - Feb 1 1991

Keywords

  • antiarrhythmic agents
  • cardiac Purkinje fibers
  • disopyramide
  • recovery of V
  • restitution of APD

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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