Distinguishing the effects of convective and diffusive O2 delivery on (V) over dotO2 on-kinetics in skeletal muscle contracting at moderate intensity

With current techniques, experimental measurements alone cannot characterize the effects of oxygen blood-tissue diffusion on muscle oxygen uptake ((V) over dotO(2)) kinetics in contracting skeletal muscle. To complement experimental studies, a computational model is used to quantitatively distinguish the contributions of convective oxygen delivery, diffusion into cells, and oxygen utilization to (V) over dotO(2) kinetics. The model is validated using previously published experimental (V) over dotO(2) kinetics in response to slowed blood flow (Q) on-kinetics in canine muscle (tau(Q) = 20 s, 46 s, and 64 s) [Goodwin ML, Hernandez A, Lai N, Cabrera ME, Gladden LB. J Appl Physiol. 112:9-19, 2012]. Distinctive effects of permeability-surface area or diffusive conductance (PS) and Q on (V) over dotO(2) kinetics are investigated. Model simulations quantify the relationship between PS and Q, as well as the effects of diffusion associated with PS and Q dynamics on the mean response time of (V) over dotO(2). The model indicates that PS and Q are linearly related and that PS increases more with Q when convective delivery is limited by slower Q dynamics. Simulations predict that neither oxygen convective nor diffusive delivery are limiting (V) over dotO(2) kinetics in the isolated canine gastrocnemius preparation under normal spontaneous conditions during transitions from rest to moderate (submaximal) energy demand, although both operate close to the tipping point.