How to measure first-order hepatic transfer coefficients by distributed modeling of a recirculating rat liver perfusion system.

A digital computer is used to simulate solute disappearance curves evolving in the reservoir of a rat liver perfusion system. The results show that it is feasible to obtain good estimates of these kinetic parameters with only approximate information about the distribution of sinusoidal flows and the transfer function of the nonexchanging vasculature. By contrast satisfactory estimates of the transfer coefficients for uptake and efflux (but not excretion) are critically dependent on accurate measurements of the system transit times. A perfusion system suitable for implementing the method is tested and found to maintain normal liver function for upward of 60 min. The means to achieve the required volume and flow measurements are discussed, and an empirical criterion is developed for recognizing disappearance curves whose information content is too low to yield reliable results.