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Chronic Left‐Ventricular Dysfunction Increases Oxidative Stress in Skeletal Muscle: Potential Mechanism of Cardiac Cachexia
Author(s) -
SemprunPrieto Laura,
Sukhanov Sergiy,
Bhutto Junaid,
Titterington Jane,
Delafontaine Patrick
Publication year - 2009
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.23.1_supplement.1007.2
Subject(s) - medicine , heart failure , cardiology , oxidative stress , atrophy , myocardial infarction , wasting , endocrinology , pathogenesis , skeletal muscle , ligation , myocyte
Skeletal muscle (SM) atrophy during congestive heart failure is a process associated with a poor prognosis whose pathogenesis remains poorly understood. To determine if there is an increase in oxidative stress in SM atrophy induced by congestive heart failure, we used a murine model of chronic left‐ventricular dysfunction (CLVD) provoked by myocardial infarction. The left coronary artery was ligated in 8‐12 week old FVB mice (LAD, n=7) and sham‐operated mice were used as controls (ctr, n=12). LAD‐ligated mice had significant left‐ventricular dysfunction at 12 weeks by echocardiography (% FS, ctr, 47.24 ± 4.4% vs. LAD, 28.6 ± 4.7%; p<0.05, LVDs, ctr, 4.4 ± 0.4mm vs. LAD, 3.6 ± 0.1mm, p<0.01; LVDd, control 1.9 ± 0.1mm vs. LAD, 3.1 ± 0.5mm, p<0.01). In addition, LAD ligation produced significant SM atrophy as evidenced by a reduced body weight (ctr, 29.61 ± 0.37g vs. LAD, 27.76 ± 0.68g, p<0.05), SM weight (gastrocnemius, GM) (ctr, 133.9 ± 2.2mg vs. LAD, 126.3 ± 1.7mg, p<0.05), GM fiber cross‐sectional area (control 1292.2 ± 70.1 μm 2 , n=5, vs. LAD, 934.1 ± 10.7 μm 2 , n=2, p<0.05), and a significant shift in the myofiber size distribution towards smaller size fibers (p<0.01). SM wasting was associated with a 51% increase in muscle superoxide levels as quantified by staining GM cross‐sections with superoxide‐sensitive dye dihydroethidium (relative DHE fluorescence, ctr, 18.20 ± 2.9 vs. LAD, 27.40 ± 5.4, p<0.05). In summary, CLVD produces an increase in oxidative stress that is associated with progressive muscle atrophy.