Effects of lung ventilation-perfusion and muscle metabolism-perfusion heterogeneities on maximal O2 transport and utilization

Previous models of O-2 transport and utilization in health considered diffusive exchange of O-2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation-perfusion and skeletal muscle metabolism-perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O-2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O-2 uptake (<(V)over dot>(O2)) and on mitochondrial P-O2 (P-mO2). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial PO2 (PaO2) at sea level by 32mmHg, but muscle <(V)over dot>(O2) by only 122 ml min(-1) (-3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced PaO2 by less than 1mmHg and V.O2 by 32mlmin(-1) (-2.4%). Skeletal muscle heterogeneity led to a wide range of potential PmO2 among muscle regions, a range that becomes narrower asV. MAX increases, and in regions with a low ratio of metabolic capacity to blood flow, PmO2 can exceed that of mixed muscle venous blood. For patients with severe COPD, peak V.O2 was insensitive to substantial changes in the mitochondrial characteristics for O-2 consumption or the extent of muscle heterogeneity. This integrative computational model of O-2 transport and utilization offers the potential for estimating profiles of PmO2 both in health and in diseases such as COPD if the extent for both lung ventilation-perfusion and tissue metabolism-perfusion heterogeneity is known.