Preload induces troponin I degradation independently of myocardial ischemia

Background - Although global ischemia induces troponin I (TNT) degradation, regional ischemia does not. We hypothesized that this disparity is related to 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 nun Hg in the absence of ischemia produced pronounced TnT degradation (27 kDa versus 31 kDa bands: 16.4±3.6% versus 4.7±1.9% in immediately excised controls, P<0.05). TnI degradation could be blocked by preventing the activation of endogenous calpains with 25/μmol/L calpeptin (4.3±0.6%). This improved function, with left ventricular systolic pressure increasing from 103±4 mm Hg to 137±7 mm Hg (P±0.05). Eliminating elevations in preload after global ischemia-induced stunning also prevented TnT degradation. Conclusions - Calpain-mediated TnT proteolysis can be dissociated from stunning and arises from elevations in preload rather than ischemia. This raises the possibility that ongoing preload-induced TnT degradation could impair myocardial function long-term.