Transgenic mouse model of stunned myocardium

Stunned myocardium is a syndrome of reversible contractile failure that fre quently complicates coronary artery disease. Cardiac excitation is uncouple d from contraction at the level of the myofilaments, Selective proteolysis of the thin filament protein troponin I has been correlated with stunned my ocardium. Here, transgenic mice expressing the major degradation product of troponin I (TnI(1-193)) in the heart were found to develop ventricular dil atation, diminished contractility, and reduced myofilament calcium responsi veness, recapitulating the phenotype of stunned myocardium. Proteolysis of troponin I also occurs in ischemic human cardiac muscle. Thus, troponin I p roteolysis underlies the pathogenesis of a common acquired form of heart fa ilure.