Dystrophin is an
integral membrane protein involved in the stabilization of the sarcolemmal membrane in cardiac muscle. We hypothesized that the loss of membrane
dystrophin during
ischemia and reperfusion is responsible for contractile force-induced myocardial injury and that cardioprotection afforded by ischemic preconditioning (IPC) is related to the preservation of membrane
dystrophin. Isolated and perfused rat hearts were subjected to 30 min of global
ischemia, followed by reperfusion with or without the contractile blocker
2,3-butanedione monoxime (BDM). IPC was introduced by three cycles of 5-min
ischemia and 5-min reperfusion before the global
ischemia.
Dystrophin was distributed exclusively in the membrane of myocytes in the normally perfused heart but was redistributed to the myofibril fraction after 30 min of
ischemia and was lost from both of these compartments during reperfusion in the presence or absence of BDM. The loss of
dystrophin preceded uptake of the membrane-impermeable
Evans blue dye by myocytes that occurred after the withdrawal of BDM and was associated with
creatine kinase release and the development of
contracture. Although IPC did not alter the redistribution of membrane
dystrophin induced by 30 min of
ischemia, it facilitated the restoration of membrane
dystrophin during reperfusion. Also, myocyte
necrosis was not observed when BDM was withdrawn after complete restoration of membrane
dystrophin. These results demonstrate that IPC-mediated restoration of membrane
dystrophin during reperfusion correlates with protection against contractile force-induced myocardial injury and suggest that the cardioprotection conferred by IPC can be enhanced by the temporary blockade of contractile activity until restoration of membrane
dystrophin during reperfusion.