Ischemic preconditioning in rats: role of mitochondrial K-ATP channel in preservation of mitochondrial function

We examined the role of the sarcolemmal,and mitochondrial K-ATP channels in a rat model of ischemic preconditioning (IPC). Infarct size was expressed as a percentage of the area at risk (IS/AAR). IPC significantly reduced inf arct size (7 +/- 1%) versus control (56 +/- 1%). The sarcolemmal K-ATP chan nel-selective antagonist HMR-1098 administered before IPC did not significa ntly attenuate cardioprotection. However, pretreatment with the mitochondri al K-ATP channel-selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min b efore IPC partially abolished cardioprotection (40 +/- 1%). Diazoxide (10 m g/kg iv) also reduced IS/AAR (36.2 +/- 4.8%), but this effect was abolished by 5-HD. As an index of mitochondrial bioenergetic function, the rate of A TP synthesis in the AAR was examined. Untreated animals synthesized ATP at 2.12 +/- 0.30 mu mol.min(-1).mg mitochondrial protein(-1). Rats subjected t o ischemia-reperfusion synthesized ATP at 0.67 +/- 0.06 pmol.min(-1).mg mit ochondrial protein(-1); IPC significantly increased ATP synthesis to 1.86 /- 0.23 mu mol.min(-1).mg mitochondrial protein-1. However, when 5-HD was a dministered before IPC, the preservation of ATP synthesis was attenuated (1 .18 +/- 0.15 mu mol.min(-1).mg mitochondrial protein(-1)). These data are c onsistent with the notion that inhibition of mitochondrial K-ATP channels a ttenuates IPC by reducing IPC-induced protection of mitochondrial function.