INVOLVEMENT OF ATP-SENSITIVE POTASSIUM CHANNELS IN PRECONDITIONING PROTECTION

Single or multiple brief periods of ischemia (preconditioning, PC) hav e been shown to protect the myocardium from infarction during a subseq uent more prolonged ischemic insult. To test the hypothesis that openi ng of ATP-sensitive potassium channels (K-ATP) is involved in this mec hanism, either bimakalim, a K-ATP channel opener, or glibenclamide, a K-ATP channel blocker, were administered to mimic or to block precondi tioning protection in barbital-anesthetized pigs. PC was elicited by a single period of 10 min left anterior descending coronary artery (LAD CA) occlusion followed by 15 min of reperfusion before the LADCA was r eoccluded for 60 min. Instead of PC, bimakalim infusion was started 15 min before the 60 min LADCA occlusion (TCO) and stopped with the onse t of ischemia. Glibenclamide was administered either for 10 min prior to the PC protocol, before bimakalim infusion, or before TCO. Regional wall function was quantified with ultrasonic crystals aligned to meas ure wall thickening (%Delta WT). At the end of the protocol, infarct s ize was determined by incubating myocardium with p-nitrobluetetrazoliu m. In seven preconditioned pigs, infarct size was 9.9 +/- 5.1% of the risk region compared with 65.9 +/- 6.0% in the seven control pigs subj ected to 60 min of ischemia only (p<0.001). In seven pigs treated with bimakalim, infarct size was reduced to 35.3 +/- 6.6 (p<0.05 vs. contr ols). Blocking ATP-sensitive potassium channels with glibenclamide pri or to PC abolished its protective effect (infarct size, 62.2 +/- 4.5%; p<0.001 vs. PC alone). Glibenclamide also antagonized the protective effect of bimakalim (infarct size, 55.2 +/- 4.0%), but did not affect infarct size, when solely administered prior to the prolonged ischemic period (62.2 +/- 4.3%). We conclude that in swine myocardium K-ATP ch annels are involved in the protective effect of ischemic preconditioni ng, since glibenclamide completely abolished the protective effect of preconditioning, while bimakalim could - at least in part - mimic it.