Is Reduced Cell Swelling a Plausible End-Effector of Ischemic Preconditioning Protection?

Summary

Ischemic preconditioning (IPC) is an endogenous mode of cardioprotection that is induced by a cycle of brief ischemia and reperfusion. Ischemic preconditioning reduces infarct size in intact animal models, reduces reoxygenation necrosis and enzyme release in perfused hearts, delays the onset of osmotic fragility in isolated cardiomyocyte models and attenuates necrosis and apoptosis in cultured cardiomyocyte models. A variety of mechanisms have been proposed to mediate the cardioprotection provided by ischemic preconditioning. These include: 1) Activation of PKC and MAPK pathways; 2) Reductions in ischemic ATP depletion, electrolyte changes, or free radical generation; 3) Production of nitric oxide; and 4) Opening of the mitochondrial KATP channel. However, there is currently no clear consensus on the end-effector mechanism(s) responsible for the cardioprotection provided by ischemic preconditioning. A recent report indicates that ischemic preconditioning enhances cell volume regulation and reduces the swelling of isolated cardiomyocytes during simulated ischemia (24). Evidence relevant to the novel hypothesis that reduced cellular swelling may be an end-effector of preconditioning protection is briefly reviewed below.