Cardioprotection provided by adenosine receptor activation is abolished by blockade of the KATP channel.
Adenosine agonists and openers of the ATP-sensitive potassium (KATP) 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 (-)-N6-(2-phenylisopropyl)-adenosine (R-PIA; n = 7) replaced preconditioning ischemia. KATP 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 < 0.0005). Ado and R-PIA also reduced IS [21.1 +/- 6.8 (P < 0.01) and 11.2 +/- 7.4% (P < 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 A1-receptor agonists mimicked the cardioprotection of ischemic preconditioning. The Ado-induced limitation of IS was abolished by blockade of the KATP channel. We conclude that both Ado A1 receptors and KATP channels may be involved in ischemic preconditioning.
Van Winkle
D M
DM
Department of Anesthesiology, Oregon Health Sciences University, Portland.
Chien
G L
GL
Wolff
R A
RA
Soifer
B E
BE
Kuzume
K
K
Davis
R F
RF
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000097:blood / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013552:Swine; D013997:Time Factors
D002316:Cardiotonic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; D010660:Phenylisopropyladenosine; D000255:Adenosine Triphosphate; D008012:Lidocaine; D000241:Adenosine