Mitochondrial K(ATP) channel opening is important during index ischemia and following myocardial reperfusion in ischemic preconditioned rat hearts.
We have previously demonstrated that K(ATP)channel openers administered just prior to and throughout reperfusion induce cardioprotection in the blood-perfused canine heart. However, a recent report suggests that the mitochondrial K(ATP)channel is only a trigger of ischemic preconditioning (IPC). These recent data are, however, in contrast to most previous investigations that suggested that activation of the mitochondrial K(ATP)channel is an important downstream mediator of cardioprotection. Therefore, we examined the role of the mitochondrial K(ATP)channel as a downstream mediator of IPC in a rat model by administering the selective mitochondrial K(ATP)channel antagonist, 5-hydroxydecanoate (5-HD), at several points during IPC. Infarct size (IS) was determined by tetrazolium chloride staining and expressed as a percent of the area at risk (AAR). Control animals had an IS/AAR of 58.4+/-0.6 and IS/AAR was reduced to 6.2+/-1.7 following IPC. 5-HD (10 mg/kg), attenuated cardioprotection when administered either 5 min prior to the IPC stimulus (40.4+/-1.4), during the reperfusion phase of the IPC stimulus (39.7+/-5.9), or 5 min prior to reperfusion during prolonged ischemia (34.3+/-6.9). Additionally, when 5-HD was administered at 5 mg/kg during the reperfusion phase of index ischemia plus 5 min prior to IPC or plus during the reperfusion phase of IPC, cardioprotection was also attenuated (36.3+/-5.5 and 43.8+/-6.9, respectively). These data suggest that activation of the mitochondrial K(ATP) channel is an important downstream regulator of myocardial protection with effects lasting into the reperfusion period following prolonged ischemia.
Fryer
R M
RM
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Hsu
A K
AK
Gross
G J
GJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006321:Heart; D006439:Hemodynamics; D015640:Ion Channel Gating / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D015221:Potassium Channels; D000255:Adenosine Triphosphate