title: Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis.
abstract: BACKGROUND
  Both morphine and limb remote ischemic perconditioning (RIPer) can protect against myocardial ischemia/reperfusion injury (IRI). This experiment was designed to assess whether combined morphine and limb RIPer could provide and enhanced protection against myocardial IRI in an in vivo rat model.
  
  
  METHODS
  One hundred male Sprague-Dawley rats were randomly allocated to six groups: sham, ischemia/reperfusion (IR), ischemic preconditioning, RIPer, morphine (M), and combined morphine and remote ischemic perconditioning (M + RIPer). Ventricular arrhythmias that occurred during ischemia and early reperfusion were scored, and serum creatine kinase isoenzyme and cardiac troponin I levels were assayed. The infarct size was determined by Evans blue and triphenyl tetrazolium chloride staining. The apoptosis in the myocardial ischemic core, ischemic border, and nonischemic areas was assessed through real-time polymerase chain reaction for Bax and Bcl-2 and with the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay.
  
  
  RESULTS
  The infarct size, serum cardiac troponin I level, incidence, and score of the arrhythmias during the initial reperfusion were significantly reduced in the M + RIPer group compared with the IR group but did not differ significantly between the ischemic preconditioning and M + RIPer groups. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells were significantly decreased, and the Bcl-2/Bax ratio was significantly increased in the M + RIPer group compared with the IR group.
  
  
  CONCLUSIONS
  This experiment demonstrates that combined morphine and limb RIPer provides an enhanced protection against myocardial IRI by the Bcl-2-linked apoptotic signaling pathway.
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shi-Yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xin-Long
authors.initials: XL
authors.lastname: Cui
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: xuefushan@aliyun.com.
authors.forename: Fu-Shan
authors.initials: FS
authors.lastname: Xue
authors.affiliation: Department of Statistics, University of Missouri-Columbia, Columbia, Missouri.
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Gao-Pu
authors.initials: GP
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Gui-Zhen
authors.initials: GZ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D003131:Combined Modality Therapy; D006614:Hindlimb / Q000098:blood supply; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: Cardioprotection; Ischemia/reperfusion injury; Limb remote ischemic perconditioning; Morphine perconditioning