Abstract 14371: The Enhanced Oxidative Stress is Associated with Skeletal Muscle Abnormalities in Patients with Heart Failure
Background: Enhanced oxidative stress is known to be a hallmark of myocardial abnormalities in heart failure (HF). Reduced aerobic exercise capacity is caused by the skeletal muscle abnormalities such as the impaired energy metabolism in patients with HF.
Hypothesis: We thus hypothesized that the enhanced oxidative stress was associated with skeletal muscle abnormalities in HF.
Methods: The incremental exercise tests with a cycle ergometer were performed in 10 male HF patients due to idiopathic dilated cardiomyopathy (left ventricular ejection fraction<40%, NYHA I-III), and 9 age-matched male control subjects. Plasma SOD activities and thiobarbituric acid reactive substances (TBARS) were measured as an antioxidant and oxidative stress marker, respectively. Muscular phosphocreatine (PCr) during unilateral plantar flexion (0.67Hz for 4 min) with a constant load of 20% one-repetition-maximum was measured by using 31P-magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL), the balance between uptake and oxidation of fatty acid, was measured in resting leg muscle by 1H-MRS.
Results: Plasma SOD activities were significantly decreased, and TBARS were significantly increased in HF compared to control. Peak oxygen uptake (peak VO2; 20.4±4.2 vs. 32.9±5.1 mL/kg/min, P<0.01) was significantly lower in HF compared to control. Maximal PCr loss during exercise was significantly greater in HF (50±17 vs. 19±6 %, P<0.01), indicating that ATP production was decreased in the skeletal muscle mitochondria. IMCL was significantly increased in HF (3.2±1.1 vs. 1.5±1.0 mmol/kg wet weight, P<0.01), indicating that fatty acid oxidation was impaired in the skeletal muscle mitochondria. Plasma SOD activities were significantly correlated with peak VO2 (r=-0.68, P<0.01), maximal PCr loss (r=-0.69, P<0.01), and IMCL (r=-0.44, P<0.05). TBARS were also significantly correlated with peak VO2 (r=-0.58, P<0.01), maximal PCr loss (r=0.63, P<0.01), and IMCL (r=0.52, P<0.05).
Conclusions: The enhanced oxidative stress was closely correlated with skeletal muscle abnormalities, which induced the reduced aerobic exercise capacity. Oxidative stress may play an important role in the association between skeletal muscle failure and heart failure.
- © 2011 by American Heart Association, Inc.