Transgenic Mouse Model of

Stunned myocardium is a syndrome of reversible contractile failure that fre-quently complicates coronary artery disease. Cardiac excitation is uncoupled from contraction at the level of the myoÞlaments. Selective proteolysis of the thin Þlament protein troponin I has been correlated with stunned myocardium. Here, transgenic mice expressing the major degradation product of troponin I ( TnI1Ð193) in the heart were found to develop ventricular dilatation, diminished contractility, and reduced myoÞlament calcium responsiveness, recapitulating the phenotype of stunned myocardium. Proteolysis of troponin I also occurs in ischemic human cardiac muscle. Thus, troponin I proteolysis underlies the pathogenesis of a common acquired form of heart failure. Coronary artery disease remains the leading cause of death in Western society, despite ma-jor strides in the treatment of acute coronary occlusion and myocardial infarction. The goal of therapy in these syndromes is prompt rees