Acute high-intensity exercise and skeletal muscle mitochondrial respiratory function: The role of metabolic perturbation.

Recently it was documented that, fatiguing, high-intensity exercise resulted in a significant attenuation in maximal skeletal muscle mitochondrial respiratory capacity, potentially due to the intramuscular metabolic perturbation elicited by such intense exercise. Utilizing intrathecal fentanyl to attenuate afferent feedback from group III/IV muscle afferents, permitting increased muscle activation and greater intramuscular metabolic disturbance, this study aimed to better elucidate the role of metabolic perturbation on mitochondrial respiratory function. Eight young, healthy males performed high-intensity cycle exercise in control (CTRL) and fentanyl-treated (FENT) conditions. Liquid chromatography-mass spectrometry and high resolution respirometry were employed to assess metabolites and mitochondrial respiratory function, respectively, pre- and post-exercise in muscle biopsies from the vastus lateralis. Compared to CTRL, FENT yielded a significantly greater exercise-induced metabolic perturbation (PCr: -67 vs. -82%, Pi: 353 vs. 534%, pH:-0.22 vs. -0.31, lactate: 820 vs. 1160%). Somewhat surprisingly, despite this greater metabolic perturbation in FENT compared to CTRL, with the only exception of respiratory control ratio (RCR) (-3 and -36%) for which the impact of FENT was significantly greater, the degree of attenuated mitochondrial respiratory capacity post-exercise was not different between CTRL and FENT, respectively, as assessed by maximal respiratory flux through complex I (-15 and -33%), complex II (-36% and -23%), complex I+II (-31 and -20%), and state 3CI+CII control ratio (-24 and -39%). Although a basement effect cannot be ruled out, this failure of an augmented metabolic perturbation to extensively further attenuate mitochondrial function questions the direct role of high-intensity exercise-induced metabolite accumulation in this post exercise response.