Myocardial preservation specific for cardiomyocytes

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Objective : Dystrophin is a membrane protein that protects the sarcolemma from oncosis induced by physical stress. Because ischemic preconditioning (IPC) protects mitochondria and prevents oncosis during reperfusion, we hypothesized that dystrophin is a target of IPC distal to mitochondrial protection. Methods and Results : The isolated rat hearts were subjected to 30 minutes ischemia followed by reperfusion. IPC was introduced by 3 cycles of 5 minutes ischemia and 5 minutes reperfusion. The loss of sarcolemmal dystrophin and myocardial ATP during ischemia was similar in the control and the IPC heart. Similar loss of sarcolemmal dystrophin and myocardial ATP was observed when the heart was treated with 2,4-dinitrophenol (DNP), an uncoupler of mitochondrial respiration, or oligomycin, an inhibitor of mitochondrial F_1F_0-ATPase. However, the IPC heart increased sarcolemmal dystrophin during reperfusion associated with an increase in tetramethylrhodamine ethylester (TMRE) uptake, an indicator of mitochondrial membrane potential (Δψm), and myocardial ATP and inhibition of myocyte oncosis. The increase in relocalization of sarcolemmal dystrophin and myocardial ATP mediated by IPC was inhibited by treatment with DNP or oligomycin during reperfusion. Moreover, the ischemic IPC heart mitochondria increased relocalization of dystrophin from the insoluble to the soluble fractions associated with increased ATP generation in vitro in a DNP and oligomycin-sensitive manner. Conclusions : These results suggest that enhanced relocalization of dystrophin to the sarcolemma during reperfusion may be a mechanistic link between IPC-mediated improvement of mitochondrial function and its protection against oncosis upon reperfusion.