Near-infrared Spectroscopy Estimation Of Combined Muscle Oxidative Capacity And Oxygen Diffusion Capacity In Humans

Abstract

With age, skeletal muscle mitochondria lose their oxidative capacity and their ability to respond to energy demand. These phenomena can lead to a reduction in skeletal muscle oxygen consumption, atrophy, and increased risk of developing age-related diseases such as sarcopenia. Whether age-derived changes in mitochondrial function correspond to structural changes in the mitochondrial reticulum remains unknown. PURPOSE: Investigate age-related changes in mitochondrial morphology and function using primary skeletal muscle cells derived from healthy young and old men. METHODS: Primary skeletal muscle progenitor cells (SkM) derived from the Rectus abdominis muscle of healthy active 18-19-year-old men (SkM Young), and 66-69-year-old men (SkM Old) were obtained from Cook MyoSite Inc. (Pittsburgh, PA). The mitochondrial network was analyzed in live cells using confocal microscopy. Oxygen Consumption Rate (OCR) was measured in intact cells using extracellular flux assays and a Seahorse analyzer (Agilent Technologies

Crossing the final frontier: oxygen transport at the blood–myocyte boundary

“…By creative use of near‐infrared spectroscopy (NIRS), and using timed circulatory occlusions, this is explicitly the knowledge gap that Pilotto et al. (2022) seek to bridge. In so doing they bring us closer to understanding what is happening functionally in muscle capillaries during exercise in humans and how that might determine DO 2 .…”

“…For instance, in both ageing (McGuire et al., 2001) and HF (Poole et al., 2018, 2020), impaired peripheral O 2 extraction and reduced DO 2 (due, in part, to fewer capillaries supporting RBC flux), respectively, limit blood–myocyte O 2 flux. Future investigations using Pilotto et al.’s (2022) technique, with manipulation of muscle O 2 supply (e.g. via altered inspired O 2 , systemic haematocrit, vasodilation), will yield crucial mechanistic insights into the limitations to muscle O 2 delivery across its final frontier from blood to myocyte.…”

“…The slope of Fick's law line radiating from the origin reflects muscle O 2 diffusing capacity, DO 2 , which is determined primarily by the number of red blood cells in flowing capillaries adjacent to the contracting myocytes (see top inset depicting microvascular determinants of DO 2 ). Pilotto et al.’s (2022) novel technique measures $$\dot{\rm V}{\rm O}_{2}$$max of the interrogated muscle (see mitochondrial reticulum inset) and also provides an estimate of DO 2 . B , $$\dot{\rm V}{\rm O}_{2}$$max is plotted for individuals with heart failure with reduced ejection fraction (HFrEF, dashed lines) and healthy control subjects (solid lines).…”

“…Note that the HF patients exhibit attenuated perfusional (Fick principle shifted downward) and diffusional (decreased slope of the Fick's law line, DO 2 ) conductances that conflate to reduce $$\dot{\rm V}{\rm O}_{2}$$max (redrawn from Poole et al., 2018). Application of Pilotto et al.’s (2022) technique to HF and other patient populations may be invaluable in assessing the mechanisms of exercise intolerance and efficacy of therapeutic interventions in these individuals.…”

“…Pilotto et al. (2022) analysed recovery kinetics within the vastus lateralis muscle under conditions of adequate (high O 2 ) and limited (low O 2 placing greater dependence on muscle DO 2 ) muscle oxygenation. The high O 2 condition O 2 recovery kinetics estimated muscle oxidative capacity whereas the delta high–low O 2 denoted a finite DO 2 and related closely with capillary density.…”