The protection by ischemic preconditioning against myocardial ischemia- and reperfusion-induced arrhythmias is not mediated by ATP-sensitive potassium channels in rats.
BACKGROUND
Single or multiple brief periods of myocardial ischemic preconditioning (PC) limits ischemia- and reperfusion-induced arrhythmias. This study tested whether PC protects against ischemia/reperfusion-induced arrhythmias and, if so, whether the protective effect was mediated by the opening of ATP-sensitive (KATP) channels.


METHODS
In protocol 1, the effects of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on the development of arrhythmias after a coronary occlusion of 5, 10, or 20 minutes followed by 10 minutes of reperfusion were studied in rats. In protocol 2, solvent or a KATP channel blocker (glyburide [0.64 mg/kg body weight delivered intravenously]) was administered 5 minutes before PC. In a second group, glyburide was administered immediately after PC. In a third group, solvent, glyburide, or a KATP channel opener (pinacidil [0.16 mg/kg delivered intravenously]) was administered 5 minutes before coronary occlusion for 5 minutes without PC.


RESULTS
In protocol 1, PC significantly reduced the ischemia-induced ventricular premature beats (VPBs) and ventricular tachycardia (VT), and it abolished ischemia-induced ventricular fibrillation (VF) during 10 or 20 minutes of coronary artery occlusion. PC also significantly reduced reperfusion-induced ventricular arrhythmias after 5 or 10 minutes of coronary artery occlusion; this effect of PC, however, was lost during reperfusion after 20 minutes of coronary occlusion. In protocol 2, PC again produced a marked reduction in reperfusion-induced arrhythmias and abolished the incidence of VPBs during 5 minutes of ischemia as well as the incidence of irreversible VF during reperfusion, whereas glyburide did not block the protective effect of PC on ischemia- and reperfusion-induced arrhythmias. Glyburide administered in non-PC animals did not reduce ischemia- and reperfusion-induced arrhythmias, nor did pinacidil.


CONCLUSIONS
The protective effect of PC was not attenuated by glyburide. These results suggest that the protective effect of PC in ischemia- and reperfusion-induced arrhythmias is not likely to be related to activation of KATP potassium channels during ischemia in rats.
Lu
H
H
Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Remeysen
P
P
De Clerck
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide