Tissue salvage for severely ischemic myocardium requires timely reperfusion by thrombolysis, angioplasty, or bypass. However, full recovery of left ventricular function often takes days to weeks. This is partly the effect of the ischemia, which causes glycogen depletion, cellular acidosis, lactate, free radical and hydrogen ion accumulation, decreased high-energy phosphates and adenine nucleotides, and mild mitochondrial and intracellular edema. However, it is also the effect of the two-faced process of reperfusion itself, which activates an inflammatory cascade manifested as functional impairment (stunning), platelet activation and thrombosis, arrhythmias, calcium loading and apoptosis in critically injured myocytes. A burst of oxygen radicals in the bed-at-risk promotes lipid peroxidation, membrane damage, microvascular obstruction, and no-reflow in the reperfused myocardium. Nevertheless, provided reperfusion is instituted within 2 to 3 hours of ischemia onset, the extent of salvage significantly exceeds the extent of lethal injury. It is hoped that this window can be widened by combining intervention with protective reperfusion cocktails containing hyperosmotic agents, calcium antagonists, and/or free radical inhibitors with the pharmacological recruitment of putative preconditioning mediators, such as the sarcolemmal KATP channel...