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J Appl Physiol (August 3, 2006). doi:10.1152/japplphysiol.00533.2006
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Submitted on May 11, 2006
Accepted on July 26, 2006

A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model

Peter Condorelli1, Hye-Won Shin2, Anna S. Aledia3, Philip E Silkoff4, and Steven C George5*

1 Biomedical Engineering, University of California, Irvine, California, United States
2 Biomedical Engineering, University of California, Irvine, Irvine, California, United States
3 Medicine, University of California Irvine Medical Center, Orange, California, United States; Biomedical Engineering, University of California, Irvine, Irvine, California, United States
4 Drexel University, Philadelphia, Pennsylvania, United States
5 Biomedical Engineering, University of California, Irvine, Irvine, California, United States; Chemical Engineering and Materials Science, University of California, Irvine, Irvine, California, United States

* To whom correspondence should be addressed. E-mail: scgeorge{at}uci.edu.

The most common technique employed to describe the pulmonary exchange features of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm which characterizes NO exchange using multiple constant flow exhalations and a model which considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows greater than 100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n=8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared to the 2CM, estimates (mean±SD) from the TMAD for the maximum airway flux are statistically higher (J'awNO= 770±470 pl/s compared to 440±270 pl/s), whereas estimates for the steady state alveolar concentration are statistically lower (CANO = 0.66±0.98 ppb compared to 1.2±0.8 ppb). Furthermore, CANO from the TMAD is not different from zero. We conclude that proximal NO production (airways) is larger than previously predicted with the 2CM, and that peripheral NO is near zero in healthy subjects.




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