Li, M. H., J. Hildebrandt, and M. P. Hlastala. Quantitative analysis of transpleural flux in the isolated lung. J. Appl. Physiol. 82(2): 545-551, 1997.In this study, the loss of inert gas through the pleura of an isolated ventilated and perfused rabbit lung was assessed theoretically and experimentally. A mathematical model was used to represent an ideal homogeneous lung placed within a box with gas flow (box) surrounding the lung. The alveoli are assumed to be ventilated with room air (A) and perfused at constant flow () containing inert gases (x) with various perfusate-air partition coefficients (_p,x). The ratio of transpleural flux of gas (pl_x) to its total delivery to the lung via pulmonary artery ( ), representing fractional losses across the pleura, can be shown to depend on four dimensionless ratios: 1) _p,x, 2) the ratio of alveolar ventilation to perfusion (A/ ), 3) the ratio of the pleural diffusing capacity (Dpl_x) to the conductance of the alveolar ventilation (Dpl_x /A_g, where _g is the capacitance coefficient of gas), and 4) the ratio of extrapleural (box) ventilation to alveolar ventilation (box/A). Experiments were performed in isolated perfused and ventilated rabbit lungs. The perfusate was a buffer solution containing six dissolved inert gases covering the entire 10⁵-fold range of _p,x used in the multiple inert gas elimination technique. Steady-state inert gas concentrations were measured in the pulmonary arterial perfusate, pulmonary venous effluent, exhaled gas, and box effluent gas. The experimental data could be described satisfactorily by the single-compartment model. It is concluded that a simple theoretical model is a useful tool for predicting transpleural flux from isolated lung preparations, with known ventilation and perfusion, for inert gases within a wide range of .