摘要Objective To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IKATP ) of rat ventricular myocytes.Methods Isolated Langendorff perfused rat hearts were randomly assigned to five groups: ( 1 ) control group, (2)IPC group, (3) IPC + glibenclamide (GLB, 10 μmol/L) group, (4) IPC + glimepiride (GLM, 10 μmol/L) group,(5) IPC + gliclazide ( GLC, 50 μmol/L ) group. IPC was defined as 3 cycles of 5 -minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded.And the sarcolemmal IKATP of dissociated ventricular myocytes reperfused with 10 μmol/L GLB, 1 μmol/L GLM, and 1μmol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition.Results The infarct sizes of rat hearts in IPC (23.7% ± 1.3% ), IPC + GLM (24. 6% ± 1.0% ), and IPC +GLC (33. 1% ±1.3% ) groups were all significantly smaller than that in control group (43.3% ±1.8%; P ＜0. 01, n=6). The infarct size of rat hearts in IPC + GLB group (40.4% ± 1.4% ) was significantly larger than that in IPC group (P ＜0. 01, n =6). Under simulated ischemic condition, GLB ( 10 μmol/L) decreased IKATP from 20. 65 ± 7.80 to 9. 09 ± 0. 10 pA/pF (P ＜ 0. 01, n = 6), GLM ( 1 μ mol/L) did not significantly inhibit IKATP ( n = 6 ), and GLC ( 1μmol/L) decreased IKATP from 16.73 ± 0. 97 to 11.18 ± 3.56 pA/pF ( P ＜ 0. 05, n = 6).Conclusions GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.