Troponin I Degradation and Myocardial Stunning
To the Editor:
The article by Feng et al1 caused a revolution in current thinking regarding the pathomechanism involved in myocardial stunning, in that it irrefutably proved that there is no causal link between troponin I (TnI) degradation and the transiently depressed contractile function after a brief ischemic episode. However, does this fact imply that there is no answer to the question of why the myocardial force is depressed and its Ca2+ sensitivity is reduced?
Certainly, the concept of TnI degradation provided an attractive explanation for myocardial stunning.2 The existence of a link between truncated TnI molecules, altered myofibrillar Ca2+ reactivity, and overall myocardial function was firmly established on the basis of experiments with transgenic animals.3 TnI modulates myofibrillar Ca2+ sensitivity and is a substrate for Ca2+-dependent proteases such as μ-calpain. The idea of increased end-diastolic pressure and not ischemia/reperfusion as a trigger for TnI degradation provides new insight into the prevention of stunning.1 What remains is that an intracellular Ca2+ overload evokes stunning because calpastatin preserves the contractile function, irrespective of the origin of the Ca2+ overload.1 Accordingly, the proteolytic basis of myocardial stunning is preserved.
Perhaps proteins other than TnI have more to do with stunning. It is important to note that intracellular calpains damage a broad spectrum of muscle proteins and that regulatory and structural changes (eg, desmin degradation) may reduce the apparent Ca2+ responsiveness of the contractile filaments.4 Thus, myocardial stunning might be a consequence of the intricate protein alterations5 that are encountered during an ischemic/reperfusion insult. If so, the task is to find the most significant ones and to disentangle them.
Feng J, Schaus BJ, Fallavollita JA, et al. Preload induces troponin I degradation independently of myocardial ischemia. Circulation. 2001; 103: 2035–2037.
Gao WD, Atar D, Liu Y, et al. Role of troponin I proteolysis in the pathogenesis of stunned myocardium. Circ Res. 1997; 80: 393–399.
Murphy AM, Kögler H, Georgakopoulos D, et al. Transgenic mouse model of stunned myocardium. Science. 2000; 287: 488–491.
Papp Z, Van der Velden J, Stienen GJM. Calpain-I induced alterations in the cytoskeletal structure and impaired mechanical properties of single myocytes of rat heart. Cardiovasc Res. 2000; 45: 981–993.
McDonough JL, Arrell DK, Van Eyk JE. Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. Circ Res. 1999; 84: 9–20.