ADENOSINE-A(1) RECEPTORS, K(ATP) CHANNELS, AND ISCHEMIC PRECONDITIONING IN DOGS

The objective of the present study was to characterize the role of adenosine in myocardial ischemic preconditioning in the canine heart. Preconditioning with 5 min of ischemia resulted in a marked reduction in infarct size after 60 min of left circumflex coronary artery occlusion and 5 h of reperfusion in barbital-anesthetized dogs compared with dogs that were not preconditioned (4.8 +/- 1.9 vs. 27.9 +/- 4.5%; P < 0.05). Pretreatment with either the nonselective adenosine receptor antagonist PD 115199 or the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked this protective effect, although in the absence of preconditioning neither of the antagonists affected infarct size. Intracoronary infusion of two different doses of adenosine or dipyridamole over a 5-min period before a prolonged 60-min occlusion period did not mimic preconditioning; however, intracoronary infusion of a combination of adenosine and dipyridamole produced a significant reduction in infarct size (13.6 +/- 4.1%), which was abolished by pretreatment with the ATP-dependent potassium (K(ATP)) channel antagonist glibenclamide. These results suggest that activation of adenosine A1 receptors produces myocardial preconditioning in the canine heart by opening K(ATP) channels.