Preload induces troponin I degradation independently of myocardial ischemia.

Abstract:

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 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.

journal_name

Circulation

journal_title

Circulation

authors

Feng J,Schaus BJ,Fallavollita JA,Lee TC,Canty JM Jr

doi

10.1161/01.cir.103.16.2035

subject

Has Abstract

pub_date

2001-04-24 00:00:00

pages

2035-7

issue

16

eissn

0009-7322

issn

1524-4539

journal_volume

103

pub_type

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