The effect of butorphanol postconditioning on myocardial ischaemia reperfusion injury in rats

Butorphanol tartrate is a synthetic opioid partial agonist analgesic. Butorphanol targets the heart, mainly via kappa-opioid receptor (kappa-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. 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 kappa-OR nor-binaltorphimine [Nor-BNI]); Group B/G (butorphanol postconditioning + nonselective ATP-sensitive potassium (K-ATP) 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)-alpha 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). 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-alpha 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-alpha 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). These results suggest that postconditioning of butorphanol tartrate can provide a potent cardioprotective effect against myocardial ischaemic and reperfusion injury. Both the kappa-OR and the K-ATP channels were involved in this effect.