Cardioprotection provided by adenosine receptor activation is abolished by blockade of the KATP channel
Van Winkle, D.M.; Chien, G.L.; Wolff, R.A.; Soifer, B.E.; Kuzume, K.; Davis, R.F.
American Journal of Physiology 266(2 Pt 2): H829-H839
1994
ISSN/ISBN: 0002-9513 PMID: 8141383 Document Number: 425341
Adenosine agonists and openers of the ATP-sensitive potassium (K-ATP) channel have been reported to limit infarct size (IS). We tested the hypothesis that these phenomena are interdependent. Anesthetized swine underwent 60 min of coronary artery occlusion and 90 min of reperfusion. Preconditioning was elicited by two cycles comprising 10 min of occlusion and 10 min of reperfusion (n = 7 swine). An intracoronary infusion of adenosine (Ado; n = 10) or (-)-N-6-(2-phenylisopropyl)-adenosine (R-PIA; n = 7) replaced preconditioning ischemia. K-ATP channels were blocked with sodium 5-hydroxydecanoate (5-HD) in the absence (n = 6) or presence (n = 8) of R-PIA. Control pigs (n = 7) received saline vehicle. IS was assessed with tetrazolium and normalized as percentage of area at risk. Preconditioning resulted in a reduced IS compared with Control (3.9 +- 1.8 vs. 43.5 +- 6.9%, respectively; P lt 0.0005). Ado and R-PIA also reduced IS (21.1 +- 6.8 (P lt 0.01) and 11.2 +- 7.4% (P lt 0.005), respectively). 5-HD alone did not alter IS, but it abolished R-PIA-induced cardioprotection (IS 5-HD + R-PIA = 48.6 +- 13.2%). Thus Ado A-1-receptor agonists mimicked the cardioprotection of ischemic preconditioning. The Ado-induced limitation of IS was abolished by blockade of the K-ATP channel. We conclude that both Ado A-1 receptors and K-ATP channels may be involved in ischemic preconditioning.