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 Ca 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 Ca reactivity, and overall myocardial function was firmly established on the basis of experiments with transgenic animals.3 TnI modulates myofibrillar Ca sensitivity and is a substrate for Ca -dependent proteases such as -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 Ca overload evokes stunning because calpastatin preserves the contractile function, irrespective of the origin of the Ca 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 Ca 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.