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Effects of lung ventilation–perfusion and muscle metabolism–perfusion heterogeneities on maximal O 2 transport and utilization
Author(s) -
Cano I.,
Roca J.,
Wagner P. D.
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2014.286492
Subject(s) - perfusion , skeletal muscle , lung , ventilation (architecture) , cardiology , metabolism , copd , medicine , respiration , chemistry , blood flow , anatomy , physics , thermodynamics
Key points We expanded a prior model of whole‐body O 2 transport and utilization based on diffusive O 2 exchange in the lungs and tissues to additionally allow for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneities, in order to estimateV ̇ O 2and mitochondrial P O 2( P m O 2) during maximal exercise. Simulations were performed using data from (a) healthy fit subjects exercising at sea level and at altitudes up to the equivalent of Mount Everest and (b) patients with mild and severe chronic obstructive pulmonary disease (COPD) exercising at sea level. Heterogeneity in skeletal muscle may affect maximal O 2 availability more than heterogeneity in lung, especially if mitochondrial metabolic capacity ( V ̇ MAX ) is only slightly higher than the potential to deliver O 2 , but whenV ̇ MAXis substantially higher than O 2 delivery, the effect of muscle heterogeneity is comparable to that of lung heterogeneity. Skeletal muscle heterogeneity may result in a wide range of potential mitochondrial P O 2 values, a range that becomes narrower asV ̇ MAXincreases; in regions with a low ratio of metabolic capacity to blood flow, P m O 2can exceed that of mixed muscle venous blood. The combined effects of lung and peripheral heterogeneities on the resistance to O 2 flow in health decreases with altitude.Abstract 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 ̇ O 2)and on mitochondrial P O 2( P m O 2). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial P O 2( P a O 2) at sea level by 32 mmHg, but muscleV ̇ O 2by only 122 ml min −1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced P a O 2by less than 1 mmHg andV ̇ O 2by 32 ml min −1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential P m O 2among muscle regions, a range that becomes narrower as V ̇ MAXincreases, and in regions with a low ratio of metabolic capacity to blood flow, P m O 2can exceed that of mixed muscle venous blood. For patients with severe COPD, peakV ̇ O 2was 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 P m O 2both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known.