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

Abstract

reports of original investigations 595 CAN J ANESTH 55: 9 www.cja-jca.org September, 2008 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 K ATP 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 K ATP channel blocker) or 30 µM HMR1098 (sarcolemmal K ATP 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 K ATP channels do not. Objectif : Le propofol exerce des effets cardioprotecteurs, mais les mécanismes sous-jacents demeurent obscurs. Cette étude examine les effets cardioprotecteurs du propofol et son rôle dans la fonction cardiaque, notamment son effet sur l'ouverture du canal K ATP et l'inhibition de l'activité du GSK-3β dans des coeurs ischémiques puis reperfusés. Méthode : L'ischémie reperfusion (I/R) a été provoquée dans des coeurs isolés de cobayes en interrompant la per fusion

Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

“…Inactivation of GSK-3 β may result in a decrease of proinflammatory cytokines [35]. A recent study has also shown that GSK-3 β inactivation was involved in a propofol-induced protective effect against IR injury in an isolated guinea pig heart [36]. Our data showed that the changes in p-GSK-3 β paralleled the alterations of serum ALT activity and IL-1 β expression.…”

Propofol Protects the Immature Rabbit Heart against Ischemia and Reperfusion Injury: Impact on Functional Recovery and Histopathological Changes

“…Several mechanisms have been proposed to explain the cardioprotective properties of propofol which include increased phosphorylation of phospho-glycogen-synthase kinase (GSK-3 β ) [36], inhibition of MPTP opening [11], reduced lipid peroxidation and lowered inflammation [37], and modulation of calcium channel activity [17]. The reduction in levels of cytosolic calcium is unlikely to be involved in cardioprotection in immature heart.…”

Mitochondrial Molecular Basis of Sevoflurane and Propofol Cardioprotection in Patients Undergoing Aortic Valve Replacement with Cardiopulmonary Bypass

“…Several possible mechanisms of propofol action, including free radical scavenging and activation of anti-apoptotic pathway, have been proposed [25]. However, in recent years other targets of propofol cardioprotection such as protein kinase C [26], glycogen synthase kinase 3β [27] and nitric oxide synthase [28] have been suggested. Our results suggest that mitochondria are targets for propofol-induced cardioprotection.…”