title: Diet-induced obesity suppresses sevoflurane preconditioning against myocardial ischemia-reperfusion injury: role of AMP-activated protein kinase pathway.
abstract: Obesity is a major risk factor for coronary artery disease, but its impact on anesthetic-induced cardioprotective actions is unexplored. We tested whether obesity inhibits anesthetic sevoflurane-induced preconditioning and whether this effect is mediated via the AMP-activated protein kinase (AMPK) signaling pathway. Sprague-Dawley rats were fed a high-fat (HF, 45% kcal as fat) or low-fat (LF, 10% kcal as fat) diet for 12 weeks. HF-fed rats developed metabolic disturbances including visceral obesity, hyperinsulinemia, hyperleptinemia and dyslipidemia. HF- or LF-fed rats subjected to 25 min of myocardial ischemia followed by 120 min of reperfusion were assigned to the following groups: control, sevoflurane preconditioning, sevoflurane plus AMPK inhibitor ara-A or AMPK activator A769662 alone. Infarct size was similar between the two control groups. Sevoflurane preconditioning significantly reduced infarct size in LF-fed rats but failed to induce cardioprotection in HF-fed rats. Phosphorylation of AMPK and endothelial nitric oxide synthase, as well as myocardial nitrite and nitrate, were also increased by sevoflurane preconditioning in LF-fed rats but not in HF-fed rats. Pretreatment with ara-A inhibited phosphorylation of AMPK and reversed sevoflurane preconditioning-induced cardioprotection in LF-fed rats, whereas it had no effects in HF-fed rats. In addition, sevoflurane preconditioning failed to enhance reactive oxygen species (ROS) generation in the myocardium of HF-fed rats compared with LF-fed rats. Direct activation of AMPK with A769662 equally increased phosphorylation of AMPK and reduced infarct size in both LF- and HF-fed rats. The results suggest that diet-induced obesity suppresses sevoflurane preconditioning-induced cardioprotective action, probably due to a diminished effect of sevoflurane preconditioning on activation of the ROS-mediated AMPK signaling pathway.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, China Medical University, Shenyang 110001, China. tao-song-cmu@hotmail.com
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Liang-Ying
authors.initials: LY
authors.lastname: Lv
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Tian
authors.forename: Wen-Yao
authors.initials: WY
authors.lastname: Cui
authors.forename: Qiu-Shi
authors.initials: QS
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Qu
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Shi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D059305:Diet, High-Fat; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000209:etiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077149:Sevoflurane; D015398:Signal Transduction
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D000077149:Sevoflurane; D019001:Nitric Oxide Synthase; D055372:AMP-Activated Protein Kinases