Effects of Fiber Type and Size on the Heterogeneity of Oxygen Distribution in Exercising Skeletal Muscle

Abstract

The process of oxygen delivery from capillary to muscle fiber is essential for a tissue with variable oxygen demand, such as skeletal muscle. Oxygen distribution in exercising skeletal muscle is regulated by convective oxygen transport in the blood vessels, oxygen diffusion and consumption in the tissue. Spatial heterogeneities in oxygen supply, such as microvascular architecture and hemodynamic variables, had been observed experimentally and their marked effects on oxygen exchange had been confirmed using mathematical models. In this study, we investigate the effects of heterogeneities in oxygen demand on tissue oxygenation distribution using a multiscale oxygen transport model. Muscles are composed of different ratios of the various fiber types. Each fiber type has characteristic values of several parameters, including fiber size, oxygen consumption, myoglobin concentration, and oxygen diffusivity. Using experimentally measured parameters for different fiber types and applying them to the rat extensor digitorum longus muscle, we evaluated the effects of heterogeneous fiber size and fiber type properties on the oxygen distribution profile. Our simulation results suggest a marked increase in spatial heterogeneity of oxygen due to fiber size distribution in a mixed muscle. Our simulations also suggest that the combined effects of fiber type properties, except size, do not contribute significantly to the tissue oxygen spatial heterogeneity. However, the incorporation of the difference in oxygen consumption rates of different fiber types alone causes higher oxygen heterogeneity compared to control cases with uniform fiber properties. In contrast, incorporating variation in other fiber type-specific properties, such as myoglobin concentration, causes little change in spatial tissue oxygenation profiles.

Modelling capillary oxygen supply capacity in mixed muscles: Capillary domains revisited

“…A local increase in fibre area (local hypertrophy) lowers the accuracy of VP as it effectively leads to local capillary rarefaction, which is consistent with our recent predictions for homogeneous muscle tissue (Al-Shammari et al, 2012) and also the numerical observations that fibre size influences PO 2 heterogeneity (Liu et al, 2012). However, if such hypertrophies are localised to fibres with relatively low O 2 uptake (i.e.…”

“…In particular, the heterogeneity of capillary spacing may be partly determined by the heterogeneity in fibre size (Egginton et al, 1988;Egginton & Ross, 1989). Furthermore, the influence of fibre heterogeneities has been explored in numerical simulations by Liu et al (2012), who concluded that changes in the fibre size distribution and oxygen uptake associated with different fibre types were particularly influential in the context of PO 2 heterogeneity within mixed muscles. Nevertheless, it is unknown whether a strong correlation between Voronoi polygons and capillary supply areas should hold in the presence of such heterogeneities.…”

Systems biology of the microvasculature

“…By integrating a blood flow model with an oxygen diffusion/consumption model, the Popel group created a multi-scale model of oxygen transport in skeletal muscle, demonstrating the influence of muscle fiber type on oxygen distribution 35 . The simulations predicted that the distribution of muscle fiber sizes has a larger impact on O 2 distribution than O 2 consumption, myoglobin concentration or oxygen diffusivity 35 .…”

“…By integrating a blood flow model with an oxygen diffusion/consumption model, the Popel group created a multi-scale model of oxygen transport in skeletal muscle, demonstrating the influence of muscle fiber type on oxygen distribution 35 . The simulations predicted that the distribution of muscle fiber sizes has a larger impact on O 2 distribution than O 2 consumption, myoglobin concentration or oxygen diffusivity 35 . Regulation of oxygen by nitric oxide, which stimulates vascodilation and is required for normal endothelial function, has been simulated 36 , but this has not been modeled in the context of angiogenesis.…”

“…Even at rest, without disease or external perturbation, there is heterogeneity in oxygen, VEGF expression, and VEGF and VEGFR concentration gradients. This was further studied using a more detailed anatomical model that included realistic muscle fiber type distributions 35 . The expression of VEGF receptors, and thus the location of the blood vessels, was identified as the key driver of VEGF gradients (which are thought to provide chemotactic guidance to nascent sprouts).…”