Myocardial stunning refers to myocardium without morphological signs of irreversible damage, which progressively recovers function after an acute episode of ischemia, and may be part of the mechanism of hibernating myocardium. Because stunned myocardium represents viable cardiac tissue, unraveling the molecular mechanisms involving programs of cell survival may open new avenues to salvage dysfunctional cardiac tissue and prevent cell loss in patients with ischemic heart disease. The global aim is to understand the molecular mechanisms underlying the concepts of fully reversible dysfunction and preserved cell viability in stunned myocardium. The first hypothesis is that the complete functional recovery involves the regulated expression of specific genes that function to enhance cell survival and thereby protect myocardial cells from necrosis and apoptosis. The second hypothesis is that the ventricular dysfunction involves an adaptation of genes coding for proteins controlling calcium metabolism. The third hypothesis is that ischemia/reperfusion, which induces stunning and hibernation will result in expression of new genes that are not normally expressed in myocardium, or potentially novel genes not yet described. Experiments will be performed in swine models of stunning, which are relevant to human clinical conditions. The models will be studied at the genomic level and the corresponding protein level. Together, these aims will comprise the first systematic approach toward the identification of the molecular phenotype of stunning in models relevant to clinical conditions. The efforts to better understand the molecular mechanisms of fully reversible dysfunction and preserved cell viability will lead to improved diagnostic and therapeutic strategies in these important clinical syndromes.
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