Preload induces troponin I degradation independently of myocardial ischemia

Background-Although global ischemia induces troponin I (TnI) degradation, r egional ischemia does not. We hypothesized that this disparity is related t o preload-induced proteolysis, which varies as a function of the amount of myocardium at risk of ischemia, Methods and Results-Isolated rat hearts were buffer-perfused at controlled levels of preload. Increasing preload to 25 mm Hg in the absence of ischemi a produced pronounced TnI degradation (27 kDa versus 31 kDa bands: 16.4+/-3 .6% versus 4.7+/-1.9% in immediately excised controls, P<0.05). TnI degrada tion could be blocked by preventing the activation of endogenous calpains w ith 35 <mu>mol/L calpeptin (4.3+/-0.6%). This improved function, with left ventricular systolic pressure increasing from 103+/-4 mm Hg to 137+/-7 mm H g (P<0.05). Eliminating elevations in preload after global ischemia-induced stunning also prevented TnI degradation. Conclusions-Calpain-mediated TnI proteolysis can be dissociated from stunni ng and arises from elevations in preload rather than ischemia. This raises the possibility that ongoing preload-induced TnI degradation could impair m yocardial function long-term.