Model analysis of the relationship between intracellular Po2and energy demand in skeletal muscle

Abstract

On the basis of experimental studies, the intracellular O2(iPo2)-work rate (WR) relationship in skeletal muscle is not unique. One study found that iPo2reached a plateau at 60% of maximal WR, while another found that iPo2decreased linearly at higher WR, inferring capillary permeability-surface area ( PS) and blood-tissue O2gradient, respectively, as alternative dominant factors for determining O2diffusion changes during exercise. This relationship is affected by several factors, including O2delivery and oxidative and glycolytic capacities of the muscle. In this study, these factors are examined using a mechanistic, mathematical model to analyze experimental data from contracting skeletal muscle and predict the effects of muscle contraction on O2transport, glycogenolysis, and iPo2. The model describes convection, O2diffusion, and cellular metabolism, including anaerobic glycogenolysis. Consequently, the model simulates iPo2in response to muscle contraction under a variety of experimental conditions. The model was validated by comparison of simulations of O2uptake with corresponding experimental responses of electrically stimulated canine muscle under different O2content, blood flow, and contraction intensities. The model allows hypothetical variation of PS, glycogenolytic capacity, and blood flow and predictions of the distinctive effects of these factors on the iPo2-contraction intensity relationship in canine muscle. Although PS is the main factor regulating O2diffusion rate, model simulations indicate that PS and O2gradient have essential roles, depending on the specific conditions. Furthermore, the model predicts that different convection and diffusion patterns and metabolic factors may be responsible for different iPo2-WR relationships in humans.