Aim
This study sought to provide a statistically robust reference for measures of mitochondrial function from standardized highâresolution respirometry with permeabilized human skeletal muscle (ex vivo), compare analogous values obtained via indirect calorimetry, arterialâvenous O2 differences and 31P magnetic resonance spectroscopy (in vivo) and attempt to resolve differences across complementary methodologies as necessary.
Methods
Data derived from 831 study participants across research published throughout March 2009 to November 2019 were amassed to examine the biological relevance of ex vivo assessments under standard conditions, ie physiological temperatures of 37°C and respiratory chamber oxygen concentrations of ~250 to 500 Όmol/L.
Results
Standard ex vivoâderived measures are lower (Z â„ 3.01, P â€Â .0258) en masse than corresponding in vivoâderived values. Correcting respiratory values to account for mitochondrial temperatures 10°C higher than skeletal muscle temperatures at maximal exercise (~50°C): (i) transforms data to resemble (Z â€Â 0.8, P > .9999) analogous yet contextâspecific in vivo measures, eg data collected during maximal 1âleg knee extension exercise; and (ii) supports the position that maximal skeletal muscle respiratory rates exceed (Z â„ 13.2, P < .0001) those achieved during maximal wholeâbody exercise, e.g. maximal cycling efforts.
Conclusion
This study outlines and demonstrates necessary considerations when actualizing the biological relevance of human skeletal muscle respiratory control, metabolic flexibility and bioenergetics from standard ex vivoâderived assessments using permeabilized human muscle. These findings detail how crossâprocedural comparisons of human skeletal muscle mitochondrial function may be collectively scrutinized in their relationship to human health and lifespan.