Exendin-4, glucagon-like peptide-1 receptor agonist, enhances isoflurane-induced preconditioning against myocardial infarction via caveolin-3 expression

OBJECTIVE: To investigate the cardioprotective effects of isoflurane and ex - endin-4 against myocardial ischemia/reperfusion injury and the signaling pathways through which these effects are mediated. MATERIALS AND METHODS: For infarct size measurements, anesthetized mice were subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wild-type or caveolin-3 knock - out mice received isoflurane, exendin-4, or isoflu - rane with exendin-4 before ischemia index deter - mination. Caveolin-3 expression in the heart was measured by immunoblotting . RESULTS: Myocardial infarct size was smaller in the isoflurane- (1.0 minimum alveolar concen - tration (MAC)) or exendin-4- (30 ng/kg i.v.) treat - ed groups than the controls. Infarct size was not affected by isoflurane at 0.5 MAC or 3 ng/kg i.v. exendin-4, but the combination of these treat - ments reduced infarct size. Pharmacological preconditioning (isoflurane at 1.0 MAC, 30 ng/kg i.v. exendin-4, or isoflurane at 0.5 MAC with 3 ng/kg i.v. exendin-4) increased caveolin-3 protein expression in the heart after infarct induction. The cardioprotective effects of isoflurane, ex - endin-4, and isoflurane with exendin-4 were abolished in caveolin-3 knockout mice. CONCLUSIONS: The combination of isoflurane and exendin-4 reduced infarct size, but it was not more effective than either agent alone, and the cardioprotective effects of these agents are mediated by caveolin-3 expression.