Grassi 2017 J Appl Physiol (1985)
|Grassi B, Majerczak J, Bardi E, Buso A, Comelli M, Chlopicki S, Guzik M, Mavelli I, Nieckarz Z, Salvadego D, Tyrankiewicz U, Skórka T, Bottinelli R, Zoladz JA, Pellegrino MA (2017) Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism. J Appl Physiol (1985) 123:326-36.|
Grassi B, Majerczak J, Bardi E, Buso A, Comelli M, Chlopicki S, Guzik M, Mavelli I, Nieckarz Z, Salvadego D, Tyrankiewicz U, Skórka T, Bottinelli R, Zoladz JA, Pellegrino MA (2017) J Appl Physiol (1985)
Abstract: 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 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 mo of age). Forty-eight Tgαq*44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an 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) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (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 percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance.
Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O2 delivery, were mainly responsible for the functional improvement.
Copyright © 2017 the American Physiological Society.
• Keywords: Transgenic murine model, Chronic heart failure, Skeletal muscle oxidative 59 metabolism, Exercise training • Bioblast editor: Kandolf G • O2k-Network Lab: IT Udine Grassi B, IT Udine Mavelli I
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Exercise physiology;nutrition;life style Pathology: Cardiovascular
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS HRR: Oxygraph-2k