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

• Published in: Journal of cardiovascular pharmacology Vol. 41; no. 6; p. 916
• Main Authors: Csonka, Csaba, Onody, Annamária, Csont, Tamás, Ferdinandy, Péter
• Format: Journal Article
• Language: English
• Published: United States 01.06.2003
• Subjects: Adenosine Triphosphate - metabolism; Animals; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - therapeutic use; Chromatography, High Pressure Liquid; Coronary Circulation - drug effects; Cromakalim - pharmacology; Electric Stimulation; Glyburide - pharmacology; Glyburide - therapeutic use; Heart Rate - drug effects; Hydroxyl Radical - metabolism; In Vitro Techniques; Male; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - physiology; Rats; Rats, Wistar; Superoxides - metabolism; Vasodilator Agents - pharmacology; Ventricular Fibrillation - drug therapy; Ventricular Fibrillation - metabolism; Ventricular Fibrillation - physiopathology
• ISSN: 0160-2446
• DOI: 10.1097/00005344-200306000-00013

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.