Defibrillatory action of glibenclamide is independent from ATP-sensitive K+ channels and free radicals

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Abstract

This study investigated whether glibenclamide exerts a defibrillatory action and if this action is mediated by a blockade of ATP-sensitive K+ channels (KATP) or by an anti-free radical mechanism. Aerobically perfused isolated rat hearts were subjected to 10 min of pacing-induced ventricular fibrillation (VF) followed by 10 min of perfusion without pacing (post-VF period), in the presence of solvent (controls), 1 μM KATP blocker glibenclamide, 10 μM KATP opener cromakalim, and their combination, respectively. In controls, pacing-induced VF caused a significant deterioration in cardiac function in the post-VF period. Spontaneous defibrillation was 42%. Glibenclamide improved post-VF cardiac function and resulted in 100% (P < 0.05) spontaneous defibrillation. Cromakalim did not significantly affect post-VF cardiac function and the incidence of spontaneous defibrillation as compared with controls. The combination of the compounds improved cardiac function and resulted in 83% (P < 0.05) spontaneous defibrillation. In separate experiments, 2,5-dihydroxybenzoic acid formation in the perfusate as a marker of hydroxyl radical formation was measured by high-performance liquid chromatography and cardiac superoxide production was assessed by lucigenin-enhanced chemiluminescence during pacing-induced VF. Glibenclamide did not affect hydroxyl radical generation or myocardial superoxide content during VF. The conclusion is that glibenclamide exerts a defibrillatory action and improves post-VF cardiac function in rat hearts and these effects are independent from KATP and free radicals.

Original languageEnglish
Pages (from-to)916-922
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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Keywords

  • Cromakalim
  • Free radicals
  • Glibenclamide
  • K
  • Rat heart
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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