title: Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1.
abstract: BACKGROUND
  The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model.
  
  
  METHODS
  Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined.
  
  
  RESULTS
  DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression.
  
  
  CONCLUSIONS
  Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.
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, Xicheng District, 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, Xicheng District, Beijing China. Electronic address: llhfw59@163.com.
authors.forename: Lihuan
authors.initials: L
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, Xicheng District, 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, Xicheng District, Beijing China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Gong
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, Xicheng District, Beijing China.
authors.forename: Nengxin
authors.initials: N
authors.lastname: Fang
mesh_terms: D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010477:Perfusion; D017207:Rats, Sprague-Dawley
chemical_list: D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Cardioprotection; Delayed remote ischemic preconditioning; Heme oxygenase-1