Cardioprotective effects of propofol in isolated ischemia-reperfused guinea pig hearts: role of KATP channels and GSK-3beta.
OBJECTIVE
Propofol exerts cardioprotective effects, but the involved mechanisms remain obscure. The present study examines the cardioprotective effects of propofol and its role in cardiac function, including its effect on K(ATP) channel opening and the inhibition of GSK-3beta activity in ischemia-reperfused hearts.


METHODS
Ischemia-reperfusion (I/R) was produced in isolated guinea pig hearts by stopping coronary perfusion for 25 min, followed by reperfusion. The hearts were incubated for ten minutes, with or without propofol (25 or 50 microM), or for five minutes with 500 microM 5-hydroxydecanoate (a mitochondrial K(ATP) channel blocker) or 30 microM HMR1098 (sarcolemmal K(ATP) channel blocker), followed by five minutes with 50 microM propofol before ischemia. Action potentials on the anterior epicardial surface of the ventricle were monitored using a high-resolution charge-coupled device camera system, and at five minutes after reperfusion, GSK-3beta phosphorylation at the serine residue, Ser9, was examined.


RESULTS
After 35 min of reperfusion, propofol (25 and 50 microM) blunted the adverse effects of I/R and reduced infarct size (P < 0.05). In addition, prior incubation with 5-hydroxydecanoate or HMR1098 had no effect on functional recovery improved by 50 microM propofol. At five minutes after reperfusion, propofol (25 and 50 microM) shortened the duration of the action potential and increased the levels of phospho-GSK-3beta (P < 0.05).


CONCLUSIONS
Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3beta play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial K(ATP) channels do not.
Department of Anesthesiology, Sapporo Medical University School of Medicine, S-1, W-6, Chuo-ku, Sapporo 060-8543, Japan.
Noriko
N
Kamada
Noriaki
N
Kanaya
Naoyuki
N
Hirata
Saori
S
Kimura
Akiyoshi
A
Namiki
D000200:Action Potentials / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents; D003326:Coronary Circulation / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation; D015742:Propofol / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000502:physiology; D016278:Ventricular Function, Right / Q000502:physiology
D018686:Anesthetics, Intravenous; D002316:Cardiotonic Agents; D054086:KATP Channels; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D015742:Propofol