Ischemic preconditioning (IP) and myocardial hibernation (MH) are both adaptive phenomena during acute myocardial ischemia, characterized by preserved myocardial viability and attenuated alterations of energy metabolism. Recent data from isolated buffer-perfused rabbit hearts pointed to a further link between IP and MH, in that an initial stimulus of no-flow ischemia was required to permit the development of MH during subsequent sustained low-flow ischemia. In the present study, we therefore investigated in the in situ pig heart whether a brief episode of no-flow ischemia enhances the myocardial tolerance to subsequent sustained low-flow ischemia. By blocking ATP-dependent potassium channels, we attempted to further determine whether such increased tolerance to ischemia is related to IP or MH, since blockade of ATP-dependent potassium channels abolishes the cardioprotection achieved by IP but not by MH. In 8 enflurane-anesthetized pigs serving as controls (group 1), the inflow into the cannulated left anterior descending coronary artery was reduced to achieve a 90% reduction in the anterior myocardial work index (sonomicrometry) for 90 minutes. In 15 pigs (group 2), a 10-minute no-flow ischemic episode preceded 80 minutes of sustained ischemia at a blood flow reduction identical to that in pigs of group 1. In 8 additional pigs (group 3), glibenclamide was administered before the 10-minute no-flow ischemic episode. In all pigs after 120 minutes of reperfusion, infarct size (IS, percentage of area at risk) was determined by triphenyltetrazolium chloride staining. In group 2, IS was reduced (6.8 +/- 6.0% [mean +/- SD], P < .05) when compared with groups 1 (13.2 +/- 9.8%) and 3 (16.7 +/- 8.3%).(ABSTRACT TRUNCATED AT 250 WORDS)