title: Hypertrophied myocardium is refractory to sevoflurane-induced protection with alteration of reperfusion injury salvage kinase/glycogen synthase kinase 3β signals.
abstract: Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired by ventricular hypertrophy, we investigate whether anesthetic-induced cardiac protection was maintained in rat hearts with ventricular hypertrophy. Transverse aortic constriction operation was performed on male Sprague-Dawley rats to induce left ventricular (LV) hypertrophy, then sham-operated or hypertrophied rat hearts were subjected to 40 min of global ischemia and 2 h of reperfusion. The isolated hearts received 3% sevoflurane for 10 min or six cycles of 10-s ischemia/10-s reperfusion after reperfusion. The hemodynamics, infarct size, PTEN (phosphatase and tensin homolog deleted on chromosome ten), phosphorylated Akt, phosphorylated extracellular regulated protein kinase (ERK) 1/2, and phosphorylated glycogen synthase kinase 3β (GSK3β) were determined. We found the myocardial expression of PTEN, phosphorylated Akt, ERK1/2, and phosphorylated GSK3β did not significantly differ between sham-operated and transverse aortic constriction-control groups. Both sevoflurane and ischemic postconditioning significantly improved LV hemodynamics, reduced infarct size, and increased the phosphorylation of Akt, ERK1/2, and their downstream target of GSK3β in the sham-operated rat hearts. In contrast, neither sevoflurane nor ischemic postconditioning improved LV hemodynamic, reduced infarct size, and increased the phosphorylated Akt, ERK1/2, and GSK3β in hypertrophied myocardium. All the results above indicate that ventricular hypertrophy abrogated sevoflurane-induced cardioprotection against ischemia-reperfusion injury by alteration of RISK/GSK3β signals.
authors.affiliation: Department of Anesthesiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Ma
authors.forename: Fei-Jiang
authors.initials: FJ
authors.lastname: Zhang
authors.forename: Fei-Juan
authors.initials: FJ
authors.lastname: Kong
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Qian
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Yan
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008738:Methyl Ethers; D000077149:Sevoflurane; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3