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From the Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Address correspondence to: Dr. Noriaki Kanaya, Department of Anesthesiology, Sapporo Medical University School of Medicine, S-1, W-6, Chuo-ku, Sapporo 060-8543, Japan. Phone: +81-11-611-2111; Fax: +81-11-631-9683; E-mail: kanaya{at}sapmed.ac.jp
Purpose: 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 KATP channel opening and the inhibition of GSK-3β 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 µM), or for five minutes with 500 µM 5-hydroxydecanoate (a mitochondrial KATP channel blocker) or 30 µM HMR1098 (sarcolemmal KATP channel blocker), followed by five minutes with 50 µM 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-3β phosphorylation at the serine residue, Ser9, was examined.
Results: After 35 min of reperfusion, propofol (25 and 50 µM) 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 µM propofol. At five minutes after reperfusion, propofol (25 and 50 µM) shortened the duration of the action potential and increased the levels of phospho-GSK-3β (P < 0.05).
Conclusions: Propofol enhanced mechanical cardiac recovery and reduced infarct size. The data further suggest that GSK-3β play an important role in propofol cardioprotective actions during coronary reperfusion, but mitochondrial KATP channels do not.
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