Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits

Zoltan Szilvassy, Matyas Koltai, Peter Ferdinandy, Ildiko Jakab, Janos Lonovics, Thierry Tarrade, Michel Allard, Pierre G. Braquet

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Myocardial ischemia assessed by intracavital ST-segment elevation, shortening of ventricular effective refractory period (VERP), and increase in left ventricular end-diastolic pressure (LVEDP) was provoked by ventricular overdrive pacing (VOP) in conscious rabbits. Cromakalim (10 μg/kg), an ATP-sensitive K+ channel opener, and cicletanine (30 mg/kg), a cGMP-phosphodiesterase inhibitor, reduced VOP-induced ST-segment elevation and LVEDP-increase. Under resting conditions, cromakalim lowered blood pressure, increased heart rate (HR), and shortened VERP, whereas cicletanine decreased HR, prolonged VERP without changing blood pressure. Co-administration of cromakalim and cicletanine additively reduced VOP-induced ST-segment elevation, shortening of VERP, and LVEDP-increase. Cicletanine did not change cromakalim-induced hypotension but abolished reflexogenic tachycardia. This suggests that VERP shortening is not a prerequisite for the anti-ischemic effect of cromakalim, and the combination of these drugs may afford a potent and safe anti-ischemic effect without affecting hypotension induced cromakalim.

Original languageEnglish
Pages (from-to)PL125-PL130
JournalLife sciences
Volume54
Issue number9
DOIs
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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