ATP-sensitive potassium channels do not have a main role in mediating late preconditioning protection against arrhythmias and stunning in conscious sheep

• Published in: Basic research in cardiology 2002-01, Vol.97 (1), p.55-64
• Main Authors: Negroni, Jorge A, Lascano, Elena C, del Valle, Héctor F, Crottogini, Alberto J
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adenosine Triphosphate - metabolism; Animals; Anti-Arrhythmia Agents - pharmacology; Arrhythmias, Cardiac - metabolism; Consciousness; Glyburide - pharmacology; Hemodynamics - drug effects; Ischemic Preconditioning, Myocardial; Male; Myocardial Reperfusion Injury - metabolism; Myocardial Stunning - metabolism; Potassium Channel Blockers; Potassium Channels - metabolism; Sheep
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s395-002-8388-7

Although late preconditioning protects against stunning following several short periods of ischemia-reperfusion, it is not clear if it confers protection against stunning and malignant arrhythmias after a sustained reversible ischemia, and whether KATP channels are involved as triggers and/or end effectors of the protective mechanism. The purpose of this work was thus to test these issues in conscious sheep. Five groups were considered: CONT (control): the animals were submitted to 12 min ischemia followed by 2 h reperfusion; SWOP (late preconditioning): on the first day, the animals were preconditioned with 6 periods of 5 min ischemia 5 min reperfusion and 24 h later they were submitted to 12 min ischemia followed by 2 h reperfusion; GLIB: same as CONT with the KATP channel inhibitor glibenclamide (0.4 mg/kg) infused 30 min prior to the 12 min ischemia; SWOPG2: same as SWOP with glibenclamide before the 12 min ischemia; SWOPG1: same as SWOP with glibenclamide prior to the preconditioning stimulus. Percent reperfusion recovery of wall thickening fraction (% WTh) showed late preconditioning protection against stunning throughout reperfusion (SWOP vs CONT, p < 0.01). Arrhythmia severity index (ASI) also demonstrated that late preconditioning protects against malignant arrhythmias at the onset of reperfusion (CONT: 4.87 +/- 1.62 vs SWOP: 1.39 +/- 0.93, p < 0.01). Glibenclamide was unable to prevent preconditioning, both against stunning and arrhythmia incidence, when administered either before the preconditioning stimulus (SWOPG1 vs CONT, p < 0.01) or before the sustained ischemia (SWOPG2 vs GLI, p < 0.01). Results indicate that late preconditioning protects against stunning and arrhythmias following a reversible, sustained ischemia in conscious sheep and that KATP channel participation is negligible as triggers and end effectors of both types of protection.