title: The effect of butorphanol postconditioning on myocardial ischaemia reperfusion injury in rats.
abstract: OBJECTIVE
  Butorphanol tartrate is a synthetic opioid partial agonist analgesic. Butorphanol targets the heart, mainly via κ-opioid receptor (κ-OR) activation. The purpose of this study was to determine the effect and mechanism underlying butorphanol postconditioning (B-Post) on myocardial ischaemia reperfusion injury in rats.
  
  
  METHODS
  Seventy-five male Sprague-Dawley rats were randomly divided into five groups of 15 each: Group sham; Group I/R (ischaemia/reperfusion); Group B (butorphanol postconditioning); Group B/N (butorphanol postconditioning + antagonist of κ-OR nor-binaltorphimine [Nor-BNI]); Group B/G (butorphanol postconditioning + nonselective ATP-sensitive potassium (KATP) channel blocker glibenclamide [GLI]). The left coronary anterior descending artery (LAD) was occluded for 30 min, followed by a 120-min reperfusion. Blood samples were obtained at the end of reperfusion for determination of serum tumour necrosis factor (TNF)-α and interleukin (IL)-6 concentrations. The hearts were then excised for determination of myocardial infarct size by triphenyltetrazolium chloride staining. The myocardial tissues were used for determination of the expression of myocardial superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO).
  
  
  RESULTS
  Myocardial infarct size was significantly reduced in B (26.4 ± 1.83%), B/N (34.5 ± 1.56%) and B/G (31.5 ± 1.27%) Groups compared with Group I/R (46.8 ± 1.41%) (all P < 0. 001). The serum TNF-α and IL-6 concentrations and the MDA and MPO activities in the ischaemic area in B, B/N and B/G Groups were significantly lower than those in the I/R Group (all P < 0.001). In addition, myocardial infarct size, TNF-α and IL-6 concentrations and the MDA and MPO activities in B/N and B/G Groups were higher than those in the B Group (all P < 0.001). In contrast, SOD activity was significantly increased in B, B/N and B/G Groups, and SOD activity in B/N and B/G Groups was less than in the B Group (all P < 0.001).
  
  
  CONCLUSIONS
  These results suggest that postconditioning of butorphanol tartrate can provide a potent cardioprotective effect against myocardial ischaemic and reperfusion injury. Both the κ-OR and the KATP channels were involved in this effect.
authors: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors: Yun
authors: Y
authors: Wu
authors: Jing
authors: J
authors: Wan
authors: Wen-Zhon
authors: WZ
authors: Zhen
authors: Liu-Fang
authors: LF
authors: Chen
authors: Jia
authors: J
authors: Zhan
authors: Jian-Juan
authors: JJ
authors: Ke
authors: Zong-Ze
authors: ZZ
authors: Zhang
authors: Yan-Lin
authors: YL
authors: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002077:Butorphanol / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D054333:Drug Partial Agonism; D015850:Interleukin-6 / Q000097:blood; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000701:Analgesics, Opioid; D015850:Interleukin-6; D054086:KATP Channels; D017473:Receptors, Opioid, kappa; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D009195:Peroxidase; D013482:Superoxide Dismutase; D002077:Butorphanol
keywords: Butorphanol; Ischaemia reperfusion injury; KATP channel; Postconditioning; κ-OR