Skeletal muscle myofibrillar protein oxidation and exercise capacity in heart failure

Abstract

Heart failure is characterized by limited exercise tolerance and by a skeletal muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status with elevated pro-inflammatory cytokines and exaggerated free radicals production can worsen muscle damage. We have previously demonstrated in a model of heart failure, the monocrotaline treated rat, that oxidation of skeletal muscle actin, tropomyosin and myosin produces a reduction of contractile efficiency, which may further depress muscle function and exercise capacity. To investigate the presence of oxidized myofibrillar proteins in skeletal muscle of CHF patients by means of the Oxyblot technique and to correlate it with exercise capacity. We have analyzed skeletal muscle biopsies taken from six patients with class III-IV NYHA CHF and four control patients (peak VO(2) 12.8 +/- 1.9 vs. 29.7 +/- 1.7 ml/kg/min, p < 0.0001). A correlation between degree of myofibrillar oxidation and exercise capacity measured as peak VO(2) was obtained. In the skeletal muscle of CHF patient there was a much higher level of myofibrillar protein oxidation as expressed by the Oxyblot/Red Ponceau (Oxy/RP) ratio as compared to controls (2.1 +/- 0.3 vs. 1.02 +/- 0.09, p < 0.0001). The VO(2)/Oxy/RP was significantly lower in the CHF patients. Higher levels of muscle oxidation were found in patients with lower exercise capacity with an inverse correlation between Oxyblot and VO(2) values (r (2) = 0.83).