Exercise training in Tgαq*44 mice during the progression of chronic heart failure:cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism

Cardiac function, skeletal (soleus) muscle oxidative metabolism and the effects of exercise training were evaluated in a transgenic murine model (Tgαq*44) of chronic heart failure (CHF) during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e. from 10 to 12 months of age). Forty-eight Tgαq*44 mice and 43 wild-type (WT) FVB controls were randomly assigned to control groups and to groups undergoing 2 months of intense exercise training (spontaneous running on a instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype (myosin heavy chain [MHC] isoforms content; citrate synthase [CS] activity) and variables related to the energy status of muscle fibers (p-AMPK/AMPK) and mitochondrial biogenesis and function (PGC-1α). In the untrained Tgαq*44 mice functional impairments of exercise performance, cardiac function and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased % of type 1 MHC isoforms. Factors “upstream” of mitochondria were likely mainly responsible for the improved exercise performance.