INTRAISCHEMIC PRECONDITIONING - INCREASED TOLERANCE TO SUSTAINED LOW-FLOW ISCHEMIA BY A BRIEF EPISODE OF NO-FLOW ISCHEMIA WITHOUT INTERMITTENT REPERFUSION

Ischemic preconditioning (IF) and myocardial hibernation (MH) are both adaptive phenomena during acute myocardial ischemia, characterized by preserved myocardial viability and attenuated alterations of energy m etabolism. Recent data from isolated buffer-perfused rabbit hearts poi nted 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 durin g subsequent sustained low-flow ischemia. In the present study, we the refore investigated in the in situ pig heart whether a brief episode o f no-flow ischemia enhances the myocardial tolerance to subsequent sus tained low-flow ischemia. By blocking ATP-dependent potassium channels , we attempted to further determine whether such increased tolerance t o ischemia is related to IP or MH, since blockade of ATP-dependent pot assium 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 arte ry was reduced to achieve a 90% reduction in the anterior myocardial w ork index (sonomicrometry) for 90 minutes. In 15 pigs (group 2), a 10- minute no-flow ischemic episode preceded 80 minutes of sustained ische mia at a blood flow reduction identical to that in pigs of group 1. In 8 additional pigs (group 3), glibenclamide was administered before th e 10-minute no-flow ischemic episode. In all pigs after 120 minutes of reperfusion, infarct size (IS, percentage of area at risk) was determ ined by triphenyltetrazolium chloride staining. In group 2, IS was red uced (6.8+/-6.0% [mean+/-SD], P<.05) when compared with groups 1 (13.2 +/-9.8%) and 3 (16.7+/-8.3%). In group 2, subendocardial blood flow of tissue that remained viable averaged 0.06+/-0.02 mL . min(-1). g(-1). This blood flow was lower than that in groups 1 (0.11+/-0.04 mL . min (-1). g(-1), P<.05) and 3 (0.10+/-0.06 mL . min(-1). g(-1), P=NS), ind icating an increased ischemic tolerance of the myocardium in pigs of g roup 2. Conclusions are as follows: (1) A brief episode of no-flow myo cardial ischemia without intermittent reperfusion increases the tolera nce to sustained low-how ischemia. (2) The cardioprotective effect is mediated by activation of ATP-dependent potassium channels and therefo re relates to IP rather than to MH.