The role of autophagy in cardioprotection by volatile anesthetics

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Sevoflurane preconditioning(SEVO-PC) is lost if the ischemic insult is too long. We examined whether induction of autophagy prolongs SEVO-PC protection during a longer ischemic insult.Isolated guinea pigs hearts were subjected to 30 or 45min ischemia,followed by 120min reperfusion. Anesthetic preconditioning was elicited with 2% sevoflurane for ten minutes prior to ischemia. Infarct size sparing effect of SEVO-PC was seen in 30min ischemia, but not 45min ischemia.Induction of autophagy by chloramphenicol prior to ischemia restored the infarct size limiting effect of SEVO-PC lost by 45min ischemia. Western blot analysis showed that expression of Akt and glycogen synthase kinase 3beta was enhanced by induction of autophagy.The effect of autophagy on calcium-induced mitochondrial permeability transition pore(MPTP) opening in isolated mitochondria from cardiomyocytes was assessed.The restoration of SEVO-PC lost by 45min ischemia is associated with enhanced inhibition of MPTP by autophagy.