Both Metabolic Inhibition and Mitochondrial K ATP Channel Opening Are Myoprotective and Initiate a Compensatory Sarcolemmal Outward Membrane Current

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Abstract
Background— Blockade of oxidative phosphorylation may activate ATP sensitive mitochondrial potassium (mitoK ATP ) channels. We examined whether both metabolic inhibition and mitoK ATP channel openers protect both the whole organ and isolated cells from ischemia. Methods and Results— Using a Langendorff preparation, one group of isolated rabbit hearts were exposed to ischemic preconditioning (IPC) via 2 episodes of flow interruption. The second group of hearts was preconditioned with 2 episodes of either the metabolic inhibitor, sodium cyanide (NaCN), or the mitoK ATP channel opener, diazoxide. The third group of hearts was exposed to the mitoK ATP channel inhibitor, 5-hydroxydecanoic acid (5-HD) prior to preconditioning with NaCN, diazoxide or IPC. Controls had no drug infused. Then, ischemia was induced in all hearts by left anterior descending coronary artery occlusion and infarct size was determined. Compared with controls (40±3%), infarct size was significantly reduced in hearts preconditioned with NaCN, diazoxide or IPC (18±3%, 26±3%, 21±2%, respectively; P P P Conclusion— Preconditioning protects the heart through mitoK ATP . This protection also alters a surface membrane current, which may be important in myocardial protection.