Qualitative and quantitative changes in skeletal muscle from heart failure patients

Abstract

The objective of this study was to determine if functional deficits in skeletal muscle of heart failure (HF) patients are related to changes at the single fiber level. We examined protein content, ultrastructure and mechanical properties of single fibers from HF patients and sedentary controls. Overall, myosin heavy chain (MHC) protein content was reduced 19% (p<0.01) with HF. In single fibers, MHC content was reduced 15% in Type I (p=0.06) and 19% in Type IIA (p<0.04) with HF. These qualitative decreases in MHC content were associated with a 12% reduction in force production per cross‐sectional area in Type I fibers (p<0.05). No differences in thick to thin filament ratio or A‐band length were found suggesting that MHC loss occurs along the thick filament length. At low [Ca2+] (pCa 8), Type I fibers from HF examined with sinusoidal analysis produced less oscillatory work and had a higher frequency of maximum work (p<0.05), indicating an increase in myosin kinetics. At high [Ca2+] (pCa 4.5), Type I and IIA HF fibers showed similar myosin kinetics, larger elastic moduli at low oscillation frequencies and greater oscillatory work than controls (p<0.05). These results indicate that HF qualitatively modifies skeletal muscle performance at the single fiber level. Together, these qualitative and quantitative changes may conspire to impair whole muscle function in heart failure patients. Support: NIH HL‐077418 and AG‐031303.