title: Sevoflurane postconditioning reduces myocardial reperfusion injury in rat isolated hearts via activation of PI3K/Akt signaling and modulation of Bcl-2 family proteins.
abstract: Sevoflurane postconditioning reduces myocardial infarct size. The objective of this study was to examine the role of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway in anesthetic postconditioning and to determine whether PI3K/Akt signaling modulates the expression of pro- and antiapoptotic proteins in sevoflurane postconditioning. Isolated and perfused rat hearts were prepared first, and then randomly assigned to the following groups: Sham-operation (Sham), ischemia/reperfusion (Con), sevoflurane postconditioning (SPC), Sham plus 100 nmol/L wortmannin (Sham+Wort), Con+Wort, SPC+Wort, and Con+dimethylsulphoxide (DMSO). Sevoflurane postconditioning was induced by administration of sevoflurane (2.5%, v/v) for 10 min from the onset of reperfusion. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximum increase in rate of LVDP (+dP/dt), maximum decrease in rate of LVDP (-dP/dt), heart rate (HR), and coronary flow (CF) were measured at baseline, R30 min (30 min of reperfusion), R60 min, R90 min, and R120 min. Creatine kinase (CK) and lactate dehydrogenase (LDH) were measured after 5 min and 10 min reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion. Total Akt and phosphorylated Akt (phospho-Akt), Bax, Bcl-2, Bad, and phospho-Bad were determined by Western blot analysis. Analysis of variance (ANOVA) and Student-Newman-Keuls' test were used to investigate the significance of differences between groups. The LVDP, + or - dP/dt, and CF were higher and LVEDP was lower in the SPC group than in the Con group at all points of reperfusion (P<0.05). The SPC group had significantly reduced CK and LDH release and decreased infarct size compared with the Con group [(22.9 + or - 8)% vs. (42.4 + or - 9.4)%, respectively; P<0.05]. The SPC group also had increased the expression of phospho-Akt, Bcl-2, and phospho-Bad, and decreased the expression of Bax. Wortmannin abolished the cardioprotection of sevoflurane postconditioning. Sevoflurane postconditioning may protect the isolated rat heart. Activation of PI3K and modulation of the expression of pro- and antiapoptotic proteins may play an important role in sevoflurane-induced myocardial protection.
authors.affiliation: Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Li-na
authors.initials: LN
authors.lastname: Yu
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Feng-jiang
authors.initials: FJ
authors.lastname: Zhang
authors.forename: Mei-juan
authors.initials: MJ
authors.lastname: Yang
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Ding
authors.forename: Jun-kuan
authors.initials: JK
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Fang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Yan
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D003402:Creatine Kinase / Q000032:analysis; D006339:Heart Rate / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning / Q000379:methods* / Q000592:standards; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D008738:Methyl Ethers / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D018685:Anesthetics, Inhalation; D007166:Immunosuppressive Agents; D008738:Methyl Ethers; D019253:Proto-Oncogene Proteins c-bcl-2; D000077149:Sevoflurane; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase; D000077191:Wortmannin
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