Objective To evaluate the myocardial protective effects of pinacidil combined with pyrrolidine dithiocarbamate (PDTC) against ischemia-reperfusion (I/R) injury to the isolated rabbit hearts and investigate its mechanisms. Methods One-hundred and twelve Japanese long-ear white rabbits of both sexes weighing 1.8-8.2 kg were killed by a knock to the head after heparinization. Their hearts were immediately removed and mounted on Langendorff apparatus and perfused with oxygenated K-H solution at 371 . Of the 112 isolated hearts 96 were randomized into 6 groups with 16 hearts in each group of which 8 hearts underwent 60 min reperfusion and another 8 hearts 120min reperfusion after 40min global myocardial ischemia: the hearts were perfused with K-H solution in group Ⅰ(K); with St Thomas Ⅱ solution in group Ⅱ(S); with pinacidil in group Ⅲ(P); with PDTC + K-H solution in group Ⅳ(PK); with PDTC + St Thomas Ⅱ solution in group Ⅴ(PS) and with PDTC + pinacidil in group Ⅵ(PP) . The rest of the 112 hearts (16 hearts) were perfused with K-H solution for 10 min. Then myocardial tissue was obtained for immuno-histochemical examination (SABC staining) used as normal control value.(1) Time of resumption of heart beat (from the beginning of reperfusion to the resumption of heart beat) was recorded; (2) left ventricular systolic and end-diastolic pressure (LVSP, LVEDP) and + dp/dtmax were monitored; (3) effluent from coronary sinus was collected at 60 min of reperfusion for determination of TNF-? concentration and (4) myocardial tissue was obtained at the end of reperfusion for determination of expression of NF-?B p65 and ICAM-1 in myocardium. Results (1) The heart beat resumption time was significantly shorter in group PP, PS and P than in the other 3 groups (P