Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

Abstract

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. 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. 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). 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.