© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
Evidence for the involvement of the ATP-sensitive potassium channel in a novel model of hypoxic preconditioning in dogs
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
* Corresponding author. Tel. (414) 456 8627; Fax (414) 266 8460.
Objectives: The major aims of the present study were to determine if a 5 min period of hypoxic (pO2 = 30–40 mmHg) buffer perfusion of the left anterior descending (LAD) coronary artery 10 min prior to a 60-min LAD occlusion produces myocardial preconditioning (PC) and to determine if hypoxic PC is mediated via activation of ATP-sensitive potassium channels (KATP). Normoxic (pO2 = 500–600 mmHg) buffer perfusion served as a control. Methods: Barbital-anesthetized dogs were subjected to 60 min of LAD occlusion followed by 3 h of reperfusion. Hypoxic PC was produced by 5 min of LAD perfusion with hypoxic buffer followed by 10 min of blood reperfusion prior to a 60-min occlusion. A sham PC group, elicited by 5 min of LAD perfusion with normoxic buffer, served as a control. A final group of animals was treated with glibenclamide (0.3 mg/kg i.V.), a specific KATP channel antagonist, 15 min prior to hypoxic PC and 3 µM of glibenclamide was also added to the hypoxic buffer. Transmural myocardial blood flow (TMBF, ml/min/100 g) was determined by radioactive microspheres 30 min after the initiation of the prolonged 60-min occlusion and infarct size (IF/AAR) as a percent of the area at risk (AAR) was determined by triphenyltetrazolium staining. Results: There were no significant differences between groups in hemodynamics, AAR, or TMBF. Five minutes of perfusion with hypoxic buffer prior to the 60-min occlusion produced a marked reduction in myocardial infarct size as compared to control animals (control, 30 ± 7 to 9 ± 2%, hypoxic PC, P < 0.05). Five minutes of perfusion with normoxic buffer had no effect on infarct size (30 ± 6%) and pretreatment with glibenclamide completely blocked the protective effect of hypoxic PC (31 ± 7%). Conclusions: These results support the hypothesis that a brief period of hypoxic buffer perfusion can precondition the heart and that this cardioprotective effect is dependent on the opening of myocardial KATP channels.
KEYWORDS Potassium channel, ATP-sensitive; Myocardial infarction; Myocardial ischemia; Myocardial hypoxia; Dog, anesthetized
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