Protective effects of fentanyl postconditioning and remote limb ischemic postconditioning against myocardial ischemia-reperfusion injury in rats

Objective To evaluate the protective effects of fentanyl postconditioning and remote limb ischemic postconditioning (RLIP) against myocardial ischemia-reperfusion (I/R) injury in rats. Methods Thirty-nine male SD rats aged 8 weeks weighing 250-350 g were randomly allocated into 5 groups: Ⅰ group sham operation (group S, n = 5); Ⅱ group I/R ( n = 7); Ⅲ group fentanyl postconditioning (group F, n= 9); Ⅳ group RLIP (group R, n = 9) and group Ⅴ fentanyl postconditioning + RLIP (group F-R, n = 9). The animals were anesthetized with intraperitoneal 3% pentobarbital 50 mg/kg, intubated and mechanically ventilated. Myocardial I/R was induced by occlusion of anterior desending branch of left coronary artery for 30 min followed by 180 min reperfusion. Fentanyl 30 μg/kg was injected iv at 15 min of myocardial ischemia in group F and F-R In group R and F-R the animals underwent 10 min ischemia of bilateral hind limbs starting from 15 min of myocardial ischemia. HR and MAP were recorded at 5,60,120 and 180 min of reperfusion and rate-pressure product( RPP, HR × MAP) were calculated. At the end of 180 min reperfusion, arterial blood samples were obtained for measurement of the activities of plasma lactate dehydrogenase (LDH) and creatine kinase isoenzyme MB (CK-MB), and the concentration of serum cardiac troponin Ⅰ (cTnI). The animals were then sacrificed. The infarct size was evaluated by double staining with Evans blue and triphenyl tetrazolium chloride. Results Myocardial I/R significantly increased plasma LDH and CK-MB activities and serum cTnI concentration and decreased HR,MAP and RPP as compared with group S.Fentanyl postconditioning and RLIP both decreased plasma CK-MB activity, serum cTnI concentration and infarct size and increased HR, MAP and RPP in group F, R and F-R as compared with group I/R. Plasma CK-MB activity,serum cTnI concentration and RPP were significantly lower and infarct size was smaller in group F-R than in group F. The infarct size was significantly smaller and MAP and RPP were higher in group F-R than in group R.Conclusion Fentanyl postconditioning can provide a myocardial protection against I/R injury. Myocardial protection is enhanced by combination of fentanyl postconditioning and RLIP. Key words: Fentanyl; Hindlimb; Myocardial reperfusion injury; Ischemic postconditioning