To examine preconditioning induced by short periods of ventricular overdrive pacing (VOP) as compared with that induced by no-flow ischemia, we subjected isolated working rat heart to 10-min coronary artery occlusion (test ischemia) followed by 3-min reperfu-sion after three intermittent periods of VOP (10 Hz) or 5-min no-flow ischemia, respectively. In the nonprecon-ditioned group, coronary occlusion decreased aortic flow (AF) from 46.6 ± 2.4 to 13.7 ± 1.7 ml/min and increased left ventricular end-diastolic pressure (LVEDP) from 0.53 ± 0.05 to 2.02 ± 0.07 kPa. Preconditioning by VOP or no-flow ischemia significantly increased AF to 25.1 ± 2.3 ml/min (p < 0.001) and to 27.3 ± 1.4 ml/min (p < 0.001) and decreased LVEDP to 1.38 ± 0.1 kPa (p < 0.001) and to 1.65 ± 0.05 kPa (p < 0.05), respectively, after test ischemia. Glibenclamide 10-7M which blocked the antiischemic effect of the ATP-sensitive K+-channel (KATP) opener cromakalim, inhibited VOP-induced protection (AF 20.3 ± 2.3 ml/min; LVEDP 1.82 ± 0.15 kPa), but did not affect no-flow ischemia-induced preconditioning [AF 26.6 ± 2.4 ml/min (p < 0.001), LVEDP 1.60 ± 0.07 kPa (p < 0.01)]. VOP and no-flow ischemia precondition heart, however their cardioprotective mechanisms may be different in terms of KATP activation in rats.