Perfusion, diffusion and their heterogeneities limiting blood-tissue O2 transfer in muscle

The relative roles of blood flow (perfusion) and diffusion in O2 supply to exercising muscle can be estimated using a simple model consisting of an O2-consuming tissue block in contact with blood (perfusion Q, slope of O2 equilibirum curve beta) through a resistance to O2 diffusion (O2-diffusing capacity D). The decisive variable is the 'equilibration index' Y=D/(Qbeta). With decreasing Y, diffusion limitation increases and perfusion limitation decreases (Y > 3 indicates predominant perfusion limitation; 3 > Y > 0.1, combined perfusion and diffusion limitation, Y < 0.1, prevailing diffusion limitation). On the basis of literature data on humans at maximum O2 uptake, O2 supply to muscle is shown to be always limited by both perfusion and diffusion. In nomoxia, perfusion limitation is prevalent, but in hypoxia diffusion limitation becomes predominant. The underlying model assumes perfect homogeneity of muscles with respect to O2 requirement, diffusion conditions and blood flow. In numerous studies on isolated and in situ muscles a pronounced heterogeneity of blood flow has been found, also during exercise and at maximal O2 uptake. It is shown that with unequal distribution of blood flow and/or O2-diffusing capacity the efficiency of O2 transfer is reduced with reference to the homogeneous model. Therefore, the diffusing capacity value calculated on the basis of the homogeneous model is an underestimate of the true diffusing capacity and diffusion limitation is overestimated.