A two-compartment model of pulmonary nitric oxide exchange dynamics

The relativelyrecent detection of nitric oxide (NO) in the exhaled breath hasprompted a great deal of experimentation in an effort to understand thepulmonary exchange dynamics. There has been very little progress intheoretical studies to assist in the interpretation of the experimentalresults. We have developed a two-compartment model of the lungs in aneffort to explain several fundamental experimental observations. Themodel consists of a nonexpansile compartment representing theconducting airways and an expansile compartment representing thealveolar region of the lungs. Each compartment is surrounded by a layerof tissue that is capable of producing and consuming NO. Beyond thetissue barrier in each compartment is a layer of blood representing thebronchial circulation or the pulmonary circulation, which are bothconsidered an infinite sink for NO. All parameters were estimated fromdata in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of theelimination rate of NO at end exhalation (E_NO) vs. theexhalation flow rate (_E). The modelis able to simulate the shape of the NO exhalation profile and tosuccessfully simulate the following experimental features of endogenousNO exchange: 1) an inverse relationship between exhaled NOconcentration and _E, 2) the dynamic relationship between the phase III slope and_E, and 3) the positiverelationship between E_NO and_E. The model predicts that theserelationships can be explained by significant contributions of NO inthe exhaled breath from the nonexpansile airways and the expansilealveoli. In addition, the model predicts that the relationship betweenE_NO and _E can be used as anindex of the relative contributions of the airways and the alveoli toexhaled NO.