Differential role of K-ATP channels in late preconditioning against myocardial stunning and infarction in rabbits

The role of ATP-sensitive potassium (K-ATP) channels in the late phase of i schemic preconditioning (PC) remains unclear. Furthermore, it is unknown wh ether K-ATP channels serve as end effectors both for late PC against infarc tion and against stunning. Thus, in phase I of this study, conscious rabbit s underwent a 30-min coronary occlusion (O) followed by 72 h of reperfusion (R) with or without ischemic PC (6 4-min O/4-min R cycles) 24 h earlier. L ate PC reduced infarct size similar to 46% versus controls. The KATP channe l blocker 5-hydroxydecanoic acid (5-HD), given 5 min before the 30-min O, a brogated the infarct-sparing effect of late PC but did not alter infarct si ze in non-PC rabbits. In phase II, rabbits underwent six 4-min O/4-min R cy cles for 3 consecutive days (days 1, 2, and 3). In controls, the total defi cit of systolic wall thickening (WTh) after the sixth reperfusion was reduc ed by 46% on day 2 and 54% on day 3 compared with day 1, indicating a late PC effect against myocardial stunning. Neither 5-HD nor glibenclamide, give n on day 2, abrogated late PC. The K-ATP channel opener diazoxide, given on day 1, attenuated stunning, and this effect was completely blocked by 5-HD . Thus the same dose of 5-HD that blocked the antistunning effect of diazox ide failed to block the antistunning effects of late PC. Furthermore, when diazoxide was administered in PC rabbits on day 2, myocardial stunning was further attenuated, indicating that diazoxide and late PC have additive ant i-stunning effects. We conclude that K-ATP channels play an essential role in late PC against infarction but not in late PC against stunning, revealin g an important pathogenetic difference between these two forms of cardiopro tection.