Effects of postconditioning with electric vagal stimulation at different times on myocardial ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the optimum time of postconditioning with electric vagal stimulation on myocardial ischemia-reperfusion (I/R) injury in rats.Methods One hundred and twenty male Sprague-Dawley rats,aged 8 weeks,weighing 290-320 g,were randomly allocated into 6 groups (n =20 each):sham operation group (S group); I/R group; electric vagal stimulation postconditioning at 15 min of ischemia,the onset of reperfusion,and 30 and 60 min of reperfusion groups (P1-4 groups).The myocardial I/R model was established by occlusion of left anterior descending branch of coronary artery for 30 min followed by a 120 min of reperfusion.In P1-4 groups,the right vagus nerve was stimulated for 30 min with continuous electric rectangular pulses (2 ms,10 Hz,1-2 V) starting from 15 min of myocardial ischemia and the other procedures were similar to those previously described in group I/R.During the I/R period,the heart rate (HR) and systolic pressure (SP) were recorded and the rate pressure product (RPP) was calculated.Venous blood samples were collected from the jugular vein at 120 min of reperfusion for determination of serum concentrations of cardiac troponin Ⅰ (cTnI),creatine kinase MB (CK-MB),tumor necrosis factor α (TNF-α),high-mobility group box protein 1 (HMGB-1),intercellular adhension molecule 1 (ICAM-1),i nterleukin (IL)-1,IL-6 and IL-10 using ELISA.The animals were then sacrificed and myocardial infarct size was measured by Evans blue and TTC staining.The myocardial contents of TNF-α,HMGB1,ICAM-1,IL-1,IL-6 and IL-10 in ischemic regions were measured using ELISA.The development of ventricular arrhythmias at the initial 30 min of reperfusion was recorded.The severity of arrhythmias was quantified by a scoring system.Results Compared with S group,the myocardial infarct size and serum concentrations of cTnI and CK-MB in I/R and P1-4 groups,serum concentrations of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in I/R group,serum concentrations of HMGB-1,ICAM-1,IL-1 and IL-6 in P2-4 groups,and the serum concentration of IL-10 in P1 group were all significantly increased,the serum concentrations of TNF-α were significantly decreased in P1-4groups (P ＜ 0.05),while no significant changes were found in serum concentrations of HMGB-1,ICAM-1,IL-1 and IL-6 in P1 group (P ＞ 0.05).The myocardial infarct size was significantly smaller and serum concentrations of cTnI and CK-MB,both serum and myocardial levels of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in P1-4 groups,RPP,incidence and scores of ventricular arrhythmias in P1 group were all significantly lower than those in I/R group,while the myocardial content of IL-10 was significantly higher in P1 group than in I/R group (P ＜ 0.05).As compared with P1 group,RPP,incidence and scores of ventricular arrhythmias,serum concentrations of HMGB-1 and ICAM-1,myocardial content of ICAM-1 in P2-4 groups,myocardial contents of TNF-α and IL-1 in P3 group,myocardial infarct size,serum concentrations of cTnI and CK-MB,serum and myocardial levels of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in P4 group were all significantly increased,while the myocardial content of IL-10 was decreased in P4 group (P ＜ 0.05).Conclusion Postconditioning with electric vagal stimulation at 15 min of ischemia is optimal for reduction of myocardial I/R injury in rats. Key words: Vagus nerve; Electric stimulation therapy; Myocardial reperfusion injury