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Department of Chemical and Biochemical Engineering and Materials Science, University of California at Irvine, Irvine, California 92697-2575
The relatively
recent detection of nitric oxide (NO) in the exhaled breath has
prompted a great deal of experimentation in an effort to understand the
pulmonary exchange dynamics. There has been very little progress in
theoretical studies to assist in the interpretation of the experimental
results. We have developed a two-compartment model of the lungs in an
effort to explain several fundamental experimental observations. The
model consists of a nonexpansile compartment representing the
conducting airways and an expansile compartment representing the
alveolar region of the lungs. Each compartment is surrounded by a layer
of tissue that is capable of producing and consuming NO. Beyond the
tissue barrier in each compartment is a layer of blood representing the
bronchial circulation or the pulmonary circulation, which are both
considered an infinite sink for NO. All parameters were estimated from
data in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of the
elimination rate of NO at end exhalation (ENO) vs. the
exhalation flow rate (
E). The model
is able to simulate the shape of the NO exhalation profile and to
successfully simulate the following experimental features of endogenous
NO exchange: 1) an inverse relationship between exhaled NO
concentration and
E, 2) the dynamic relationship between the phase III slope and
E, and 3) the positive
relationship between ENO and
E. The model predicts that these
relationships can be explained by significant contributions of NO in
the exhaled breath from the nonexpansile airways and the expansile
alveoli. In addition, the model predicts that the relationship between
ENO and
E can be used as an
index of the relative contributions of the airways and the alveoli to
exhaled NO.
mathematical model; elimination rate; phase III; single exhalation
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