title: Delayed remote ischemic preconditioning produces an additive cardioprotection to sevoflurane postconditioning through an enhanced heme oxygenase 1 level partly via nuclear factor erythroid 2-related factor 2 nuclear translocation.
abstract: Although both sevoflurane postconditioning (SPoC) and delayed remote ischemic preconditioning (DRIPC) have been proved effective in various animal and human studies, the combined effect of these 2 strategies remains unclear. Therefore, this study was designed to investigate this effect and elucidate the related signal mechanisms in a Langendorff perfused rat heart model. After 30-minute balanced perfusion, isolated hearts were subjected to 30-minute ischemia followed by 60-minute reperfusion except 90-minute perfusion for control. A synergic cardioprotective effect of SPoC (3% v/v) and DRIPC (4 cycles 5-minute occlusion/5-minute reflow at the unilateral hindlimb once per day for 3 days before heart isolation) was observed with facilitated cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect was more pronounced in the combined group (6.76% ± 2.18%) than in the SPoC group (16.50% ± 4.55%, P < .001) or in the DRIPC group (10.22% ± 2.57%, P = .047). Subsequent analysis revealed that an enhanced heme oxygenase 1 (HO-1) expression, but not protein kinase B/AKt or extracellular signal-regulated kinase 1 and 2 activation, was involved in the synergic cardioprotective effect, which was further confirmed in the messenger RNA level of HO-1. Such trend was also observed in the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, an upstream regulation of HO-1. In addition, correlation analysis showed a significantly positive relationship between HO-1 expression and Nrf2 translocation (r = 0.729, P < .001). Hence, we conclude that DRIPC may produce an additive cardioprotection to SPoC through an enhanced HO-1 expression partly via Nrf2 translocation.
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Huatong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yuntai
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China llhfw59@163.com.
authors.forename: Lihuan
authors.initials: L
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006614:Hindlimb; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010477:Perfusion; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D008738:Methyl Ethers; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; D000077149:Sevoflurane; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Nrf2; cardioprotection; combination; delayed remote ischemic preconditioning; heme oxygenase 1; sevoflurane postconditioning