Diffusion-limited, but not perfusion-limited, compartmental models describe cerebral nitrous oxide kinetics at high and low cerebral blood flows

This study aimed to evaluate the relative importance of diffusion-limited v s. perfusion-limited mechanisms in compartmental models of blood-tissue ine rt gas exchange in the brain. Nitrous oxide concentrations in arterial and brain efferent blood were determined using gas chromatographic analysis dur ing and after 15 min of nitrous oxide inhalation, at separate low and high steady states of cerebral blood flow (CBF) in five sheep under halothane an esthesia. Parameters and model selection criteria of various perfusion- or diffusion-limited structural models of the brain were estimated by simultan eous fitting of the models to the mean observed brain effluent nitrous oxid e concentration for both bloodflow stales. Perfusion-limited models returne d precise, credible estimates of apparent brain volume but fit the low CBF data poorly. Diffusion-limited models provided better overall fit of the da ta, which was best described by exchange of nitrous oxide between a perfusi on-limited brain compartment and an unperfused compartment. In individual a nimals, during the low CBF state, nitrous oxide kinetics display ed either fast, perfusion limited behavior or slow, diffusion-limited behavior. This variability was exemplified in the different parameter estimates of the dif fusion limited models fitted to the individual animal data sets. Results su ggest that a diffusion limitation contributes to cerebral nitrous oxide kin etics.