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Chronic Bendavia therapy improves post‐infarction cardiac function and prevents adverse left ventricular remodeling in rats (652.8)
Author(s) -
Dai Wangde,
Shi Jianru,
Hale Sharon,
Kloner Robert
Publication year - 2014
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.28.1_supplement.652.8
Subject(s) - ventricular remodeling , ejection fraction , medicine , cardiac function curve , myocardial infarction , cardiology , infarction , stroke volume , sham surgery , endocrinology , heart failure , pathology , alternative medicine
Bendavia (Ben), a mitochondria‐targeting peptide, protects mitochondrial function by enhancing bioenergetics under conditions of oxidative stress, thus inhibiting ROS formation. We hypothesized that Ben therapy would benefit post‐myocardial infarction (MI) cardiac function and remodeling in rats. At 2 hours after left coronary ligation, rats were randomized to receive Ben that was delivered subcutaneously by an Alzet Osmotic Pump (3 mg/kg/day, n=28) or water (n=26). Six weeks later, scar circumference assessed by histology and expressed as percentage of total left ventricular (LV) circumference, was significantly smaller in the Ben group (39.7 ± 2.2 %) versus the water group (47.4 ± 2.5 %, p=0.024). Post‐mortem LV volume was 9.6% smaller in the Ben group (p=0.019). LV fractional shortening by echo was significantly greater in the Ben group (28.8 ± 1.7 %) than in the water group (23.8 ± 1.8 %, p=0.047). LV stroke volume was greater in the Ben group (0.257 ± 0.008 ml) versus the water group (0.231 ± 0.008 ml, p=0.029), and LV ejection fraction assessed by LV ventriculography was greater with Ben (55.3 ± 1.4%) versus water (49.3 ± 1.4%, p=0.005). Ben treatment reversed the down‐regulated expression of mitochondrial energy metabolism‐related genes at the noninfarcted infarct border assessed by PCR array. Chronic Ben therapy improved post‐MI cardiac function, prevented stretching of the scar and adverse remodeling in rats. Grant Funding Source : Supported by Stealth Peptides, Inc., Newton, Mass.