Modeling kinetics of infused (NN)-N-13-saline in acute lung injury

A mathematical model was developed to estimate right-to-left shunt (F-s) and the volume of distribution of (NN)-N-13 in alveolar gas (V-A) and shunt tissue (V-s). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes (NN)-N-13 kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of (NN)-N-13-labeled saline was injected at the onset of apnea as PET imaging and arterial (NN)-N-13 sampling were initiated. The model fit the tracer kinetics well (mean r(2) = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. F-s derived from the model correlated well with shunt estimates derived from 02 blood concentrations and from PET images. F-s was higher for LS (54 +/- 18%) than for LP (5 +/- 4%) and NP (1 +/- 1%, P < 0.01). V-A, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 &PLUSMN; 0.09) than for LP (0.96 &PLUSMN; 0.28, P < 0.01), whereas V-A, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 +/- 0.26) than for LP (0.05 +/- 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial (NN)-N-13 kinetics and provides estimates of F-s, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.