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

Abstract:

:This study investigated whether glibenclamide exerts a defibrillatory action and if this action is mediated by a blockade of ATP-sensitive K+ channels (K(ATP)) 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 microM K(ATP) blocker glibenclamide, 10 microM K(ATP) 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 K(ATP) and free radicals.

journal_name

J Cardiovasc Pharmacol

authors

Csonka C,Onody A,Csont T,Ferdinandy P

doi

10.1097/00005344-200306000-00013

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

916-22

issue

6

eissn

0160-2446

issn

1533-4023

journal_volume

41

pub_type

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