(Circulation. 2001;103:2035.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Preload Induces Troponin I Degradation Independently of Myocardial Ischemia
From the Departments of Medicine (B.J.S., J.A.F., J.M.C.), Physiology and Biophysics (J.M.C.), Biochemistry (T.-C.L.), and Surgery (J.F.) at the University at Buffalo and the Department of Veterans Affairs, Buffalo, NY.
Correspondence to John M. Canty, Jr, MD, University at Buffalo, Biomedical Research Building, Room 347, 3435 Main Street, Buffalo, NY 14214. E-mail canty{at}buffalo.edu
Background—Although global ischemia induces troponin I (TnI) 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 mm Hg in the absence of ischemia 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 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 TnI degradation.
Conclusions—Calpain-mediated TnI proteolysis can be dissociated from stunning and arises from elevations in preload rather than ischemia. This raises the possibility that ongoing preload-induced TnI degradation could impair myocardial function long-term.
Key Words: troponin I • calpain • myocardial stunning • ischemia
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