Ja. Auchampach et Gj. Gross, ADENOSINE-A(1) RECEPTORS, K(ATP) CHANNELS, AND ISCHEMIC PRECONDITIONING IN DOGS, The American journal of physiology, 264(5), 1993, pp. 1327-1336
The objective of the present study was to characterize the role of ade
nosine in myocardial ischemic preconditioning in the canine heart. Pre
conditioning 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 do
gs that were not preconditioned (4.8 +/- 1.9 vs. 27.9 +/- 4.5%; P < 0.
05). Pretreatment with either the nonselective adenosine receptor anta
gonist PD 115199 or the selective adenosine A1 receptor antagonist 8-c
yclopentyl-1,3-dipropylxanthine blocked this protective effect, althou
gh in the absence of preconditioning neither of the antagonists affect
ed infarct size. Intracoronary infusion of two different doses of aden
osine or dipyridamole over a 5-min period before a prolonged 60-min oc
clusion period did not mimic preconditioning; however, intracoronary i
nfusion of a combination of adenosine and dipyridamole produced a sign
ificant reduction in infarct size (13.6 +/- 4.1%), which was abolished
by pretreatment with the ATP-dependent potassium (K(ATP)) channel ant
agonist glibenclamide. These results suggest that activation of adenos
ine A1 receptors produces myocardial preconditioning in the canine hea
rt by opening K(ATP) channels.