Sevoflurane Postconditioning Protects Chronically-Infarcted Rat Hearts against Ischemia-Reperfusion Injury by Activation of Pro-survival Kinases and Inhibition of Mitochondrial Permeability Transition Pore Opening upon Reperfusion

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概要

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• We evaluated the cardioprotection against myocardial ischemia-reperfusion injury induced by sevoflurane postconditioning (SpostC) in chronically-infarcted rat hearts, and investigated the roles of phosphoinositide 3-kinase (PI3K)-protein kinase B/Akt (PKB/Akt), mitogen-activated extracellular regulated kinase 1/2 (MEK 1/2)-extracellular regulated kinase 1/2 (ERK 1/2), and mitochondrial permeability transition pore (mPTP). Left anterior descending (LAD) coronary artery was ligated to induce myocardial infarction in rats. Six weeks later, chronically-infarcted hearts were isolated and subjected to 30 min of global ischemia, followed by 1 h of reperfusion with Krebs-Henseleit (K-H) buffer. SpostC was administered by perfusing the hearts with K-H buffer saturated with 3% sevoflurane during the first 15 min of reperfusion. To evaluate the role of PI3K-PKB/Akt and MEK 1/2-ERK 1/2 in SpostC, PI3K inhibitor LY294002 (15 μM) and MEK 1/2 inhibitor PD98059 (20 μM) were administered alone or together with sevoflurane during the first 15 min of reperfusion. We found that exposure of 3% sevoflurane during early reperfusion significantly improved functional recovery (improved left ventricular developed pressure (LVDP), ±dp/dt, CF, HR and reduced left ventricular end-diastolic pressure (LVEDP)), decreased myocardial infarct size and reduced LDH and CK-MB release, when compared with unprotected hearts. However, these protective effects were abolished in the presence of either LY294002 or PD98059, which was accompanied by the prevention of PKB/Akt and ERK 1/2 phosphorylation, and reduction of myocardial nicotinamide adenine dinucleotide (NAD+) content. These findings suggest that sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by inhibiting mPTP opening via recruitment of PKB/Akt and ERK 1/2.

著者

• Li Libing

  Department Of Pharmacology School Of Medicine Fukushima Medical University

• Yao Yuntai

  Department of Anesthesiology, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences, Pe

• Li Lihuan

  Department of Anesthesiology, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences, Pe

• Gao Changqing

  Department of Cardiovascular Surgery and Cardiovascular Institute, General Hospital of the Peoples L

• Shi Chunxia

  Department of Anesthesiology, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences, Pe

• Gao Changqing

  Department of Cardiovascular Surgery and Cardiovascular Institute, General Hospital of the People's Liberation Army

• Li Lihuan

  Department of Anesthesiology, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College

• Yao Yuntai

  Department of Anesthesiology, Fuwai Cardiovascular Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College

• Li Libing

  Department of Cardiovascular Surgery and Cardiovascular Institute, General Hospital of the People's Liberation Army

関連論文

• Sevoflurane Postconditioning Protects Chronically-Infarcted Rat Hearts against Ischemia-Reperfusion Injury by Activation of Pro-survival Kinases and Inhibition of Mitochondrial Permeability Transition Pore Opening upon Reperfusion
• Acidic Preconditioning Inhibits Na^+/H^+ and Na^+/Ca^ Exchanger Interaction via PKCε in Guinea-Pig Ventricular Myocytes

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