Effects of lung ventilation–perfusion and muscle metabolism–perfusion heterogeneities on maximal O2 transport and utilization. (11th March 2015)

• Record Type: Journal Article
• Authors: Cano, I.; Roca, J.; Wagner, P. D.
• Is Part Of: Journal of physiology. Volume 593:Number 8(2015:Apr.)
• Page Start: 1841
• Page End: 1856
• Publication Date: 2015-03-11
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2014.286492
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="tjp6571-sec-0010" sec-type="section"> <title>Key points</title> <p> <list id="tjp6571-list-0001" list-type="bullet"> <list-item> <p>We expanded a prior model of whole‐body O<sub>2</sub> transport and utilization based on diffusive O<sub>2</sub> exchange in the lungs and tissues to additionally allow for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneities, in order to estimate <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dx9p" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0004" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> and mitochondrial <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxb6" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0005" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> (<inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxcq" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0006" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula>) during maximal exercise.</p> </list-item> <list-item> <p>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.</p> </list-item> <list-item> <p>Heterogeneity in skeletal muscle may affect maximal O<sub>2</sub> availability more than heterogeneity in lung, especially if mitochondrial metabolic capacity (<inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxg8" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0007" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:mi> MAX </mml:mi></mml:msub></mml:math></alternatives></inline-formula>) is only slightly higher than the potential to deliver O<sub>2</sub>, but when <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxhs" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0008" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:mi> MAX </mml:mi></mml:msub></mml:math></alternatives></inline-formula> is substantially higher than O<sub>2</sub> delivery, the effect of muscle heterogeneity is comparable to that of lung heterogeneity.</p> </list-item> <list-item> <p>Skeletal muscle heterogeneity may result in a wide range of potential mitochondrial <italic>P</italic><sub>O</sub><sub>2</sub> values, a range that becomes narrower as <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxj9" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0009" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:mi> MAX </mml:mi></mml:msub></mml:math></alternatives></inline-formula> increases; in regions with a low ratio of metabolic capacity to blood flow, <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxx0" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0010" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> can exceed that of mixed muscle venous blood.</p> </list-item> <list-item> <p>The combined effects of lung and peripheral heterogeneities on the resistance to O<sub>2</sub> flow in health decreases with altitude.</p> </list-item> </list> </p> </sec> <sec id="tjp6571-sec-0020" sec-type="section"> <title>Abstract</title> <p>Previous models of O<sub>2</sub> transport and utilization in health considered diffusive exchange of O<sub>2</sub> 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<sub>2</sub> 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<sub>2</sub> uptake (<inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxzh" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0011" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub><mml:mrow><mml:mo>)</mml:mo></mml:mrow></mml:mrow></mml:math></alternatives></inline-formula> and on mitochondrial <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxsx" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0012" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> (<inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxwg" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0013" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula>). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxqw" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0014" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> (<inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxrd" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0015" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">a</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula>) at sea level by 32 mmHg, but muscle <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxnv" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0016" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> by only 122 ml min<sup>−1</sup> (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dxpc" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0017" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">a</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> by less than 1 mmHg and <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dz0h" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0018" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> by 32 ml min<sup>−1</sup> (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dz11" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0019" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> among muscle regions, a range that becomes narrower as<inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dq04" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0020" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:mi> MAX </mml:mi></mml:msub></mml:math></alternatives></inline-formula> increases, and in regions with a low ratio of metabolic capacity to blood flow, <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dpqh" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0021" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> can exceed that of mixed muscle venous blood. For patients with severe COPD, peak <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dpp0" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0022" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mover accent="true"><mml:mi>V</mml:mi><mml:mo>̇</mml:mo></mml:mover><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:msub></mml:math></alternatives></inline-formula> was insensitive to substantial changes in the mitochondrial characteristics for O<sub>2</sub> consumption or the extent of muscle heterogeneity. This integrative computational model of O<sub>2</sub> transport and utilization offers the potential for estimating profiles of <inline-formula><alternatives><inline-graphic mimetype="image" xlink:href="ark:/27927/pgjj72dpng" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math display="inline" altimg="urn:x-wiley:00223751:tjp6571:equation:tjp6571-math-0023" overflow="scroll" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi mathvariant="normal">m</mml:mi><mml:msub><mml:mi mathvariant="normal">O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math></alternatives></inline-formula> both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known.</p> </sec> </abstract>