Blockade of ATP-sensitive K+ channels attenuates preconditioning effect onmyocardial metabolism in swine: Myocardial metabolism and ATP-sensitive K+channels

Objective: We investigated if blockade of ATP-sensitive K+ channels (K-ATP) abolishes the protective effect of ischemic preconditioning (IP) on myocar dial metabolism and ischemia-induced reactive hyperemia (RH) in pigs. Metho ds: IP was elicited by a single cycle of 5 min occlusion and 5 min reperfus ion of coronary artery, followed by 15 min of test ischemia and 120 min of reperfusion. Vehicle or the ATP-sensitive K+ channels (K-ATP) blocker, glib enclamide (3 or 6 mg/kg; G3 or G6) was administered before IP (groups; IP, G3 + IP, G6 + IP). As respective controls, the same treatment was performed in groups without IP (groups; C, G3, G6). Tissue levels of ATP, creatine p hosphate (CP) and intracellular pH (pHi) in the area at risk were measured by P-31-nuclear magnetic resonance spectroscopy. RH after 5 min of precondi tioning ischemia was assessed by regional myocardial blood flow. Results: A TP and pHi were preserved after 15 min of ischemia in the IP group [C/IP; A TP = 57 +/- 4/76 +/- 10% of baseline, pHi = 6.18 +/- 0.08/6.66 +/- 0.03, P < 0.05, C vs. IP]. Both doses of glibenclamide completely abolished the ATP sparing effect of IP. The high dose completely abolished pHi preservation (G6 + IP = 6.33 +/- 0.06), while the low dose showed only a partial effect (G3 + IP = 6.48 +/- 0.03). Glibenclamide did not adversely affect myocardia l metabolism in groups without IP. Glibenclamide attenuated RH after 5 min of ischemia by 30% in both subendocardium and subepicardium. Conclusions: B lockade of K-ATP abolished the preconditioning effect on myocardial metabol ism, and partially attenuated post-ischemic reactive hyperemia in pigs. The se results indicate that K-ATP activation might be involved in the mechanis ms of these phenomena, reactive hyperemia is not sufficient to induce IP pr otection. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.