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Lung Diffusing Capacities (DL ) for Nitric Oxide (NO) and Carbon Monoxide (CO): The Evolving Story
Colin D R Borland1, J Mike B Hughes2
1Department of Medicine, University of Cambridge, Cambridge, UK.
Nitric oxide (NO) and carbon monoxide (CO) gas transfer in the lungs were studied. New calculations suggest membrane diffusion capacity for CO is lower and capillary volume is higher than previously thought.
Area of Science:
- Pulmonary Physiology
- Gas Exchange Kinetics
- Respiratory Medicine
Background:
- Nitric oxide (NO) and carbon monoxide (CO) diffusing capacities (DLNO and DLCO) follow Fick's Law and chemical kinetics.
- NO transfer is primarily membrane diffusion-limited (DM), while CO transfer involves both membrane diffusion and red blood cell reaction kinetics.
- Marie Krogh's initial assumption of instantaneous CO-hemoglobin (Hb) binding was later revised by Roughton and colleagues, who demonstrated a finite reaction rate.
Purpose of the Study:
- To re-evaluate the Roughton-Forster (R-F) equation for calculating diffusing capacity of the membrane (DM) and capillary volume (Vc) using simultaneous NO and CO inhalation.
- To investigate the impact of the assumed reaction rate (θ) for NO uptake by Hb on DM and Vc calculations.
- To compare calculated DM and Vc values with morphometric data under near-maximal exercise conditions.
Main Methods:
- Utilized simultaneous single-breath inhalation of NO and CO.
- Applied the Roughton-Forster (R-F) equation, which models transfer resistance as the sum of membrane resistance (1/DM) and red cell resistance (1/θVc).
- Incorporated recent mathematical modeling suggesting an 'effectively' infinite θ for NO due to its localized reaction within the red blood cell.
Main Results:
- Initial calculations using assumed θ values yielded DMCO at 88% and Vc at 79% of morphometric values at near-maximal exercise.
- Recalculation with an 'infinite θNO' assumption significantly reduced DMCO to 53% and increased Vc to 95% of morphometric values.
- These findings highlight the sensitivity of DM and Vc calculations to the chosen θ values, particularly for NO.
Conclusions:
- The assumption regarding the reaction kinetics of NO with hemoglobin critically influences the calculated membrane diffusing capacity (DMCO) and capillary volume (Vc).
- An 'effectively' infinite θNO leads to substantially different estimates of DMCO and Vc compared to previous models.
- Accurate determination of gas transfer parameters in the lung requires precise understanding and modeling of red blood cell uptake kinetics for both CO and NO.
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