title: Isoflurane preconditioning confers cardioprotection by activation of ALDH2.
abstract: The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.
authors.affiliation: Department of Cardiology, The First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Xiao-E
authors.initials: XE
authors.lastname: Lang
authors.forename: Xiong
authors.initials: X
authors.lastname: Wang
authors.forename: Ke-Rang
authors.initials: KR
authors.lastname: Zhang
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Lv
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Jin
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D021381:Protein Transport; D051381:Rats
chemical_list: D002316:Cardiotonic Agents; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D051744:Protein Kinase C-epsilon; D052279:Creatine Kinase, MB Form