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Strain‐Dependence in Susceptibility to Heart Failure: Role of Mitochondria
Author(s) -
Ascah Alexis,
Marcil Mariannick,
Matas Jimmy,
OliverDussault Christelle,
Deschepper Christian,
Burelle Yan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.751.7
Subject(s) - decompensation , volume overload , heart failure , cardiology , medicine , mitochondrion , strain (injury) , endocrinology , biology , biochemistry
The purpose of this study was to compare two genetically different strains of rats submitted to overload‐induced ventricular remodelling to examine factors that predispose to the progression toward heart failure. Volume overload was induced by an aorto‐caval fistula (ACF) in SD and WKHA male rats, and hearts were studied at 4, 8 and 12 weeks after surgery. Compared to WKHA, ACF‐induced LV hypertrophy and dysfunction progressed more rapidly in SD rats, and functional recovery of SD hearts to I‐R was poorer vs WKHA during the compensated phase of disease. At later times (up to 40 weeks after ACF), SD rats (but not WKHA rats) died progressively of acute cardiac decompensation. Both strains developped a vulnerability to opening of the PTP, as measured in situ (in ischemic‐reperfused hearts using the mitochondrial [ 3 H]DOG entrapment method) or in isolated mitochondria submitted to in vitro stress. Increased vulnerability to PTP opening was observable beginning at 4 weeks but no differences in severity was apparent between strains. The % of collagen‐cross linking increased progressively after ACF in both strains, but to a lower extent in SD vs. WKHA hearts. These results suggest that, while mitochondrial dysfunction may participate to the negative consequences of ACF‐induced LVH in both strains, it is not responsible for the more the rapid progression to decompensation observed in SD rats. Further experiments are underway to test the differences in cardiac outcome may be due to differences in the levels of collagen‐cross linking. Funded by: CIHR, FRSQ