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 1 μmol/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 μmol/L） did not significantly inhibit IKATP （n=6）

and GLC （1 μmol/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.