Preload induces troponin I degradation independently of myocardial ischemia.
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.


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 micromol/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.
Feng
J
J
Department of Surgery, University at Buffalo, NY 14214, USA.
Schaus
B J
BJ
Fallavollita
J A
JA
Lee
T C
TC
Canty
J M
JM
D000818:Animals; D001794:Blood Pressure; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D019210:Troponin I; C071482:calpeptin; D002154:Calpain