A Multisubstrate Blood-Tissue Exchange Model for the Analysis of Indicator Dilution Curves from Whole Organs

Abstract While our earlier blood-tissue exchange models permitted consumption, consumed solute was considered as either sequestered and retained or as having reacted to form a product whose kinetics were not modeled. We have extended the four region, three barrier, axially distributed model that accounts for convection in the capillary, diffusion into the endothelial cells, ISF, and parenchymal cells (Bassingthwaighte, Wang and Chan, 1989) to account for a sequence of reactions in all regions. It uses the same sliding fluid element flow algorithm and analytic method for solving the convection-diffusion equations at each time step. Metabolic reactions are considered to be the sum of two processes: a fraction of the amount consumed goes to a product that can exchange with adjacent regions or may be further metabolized; the remainder is permanently sequestered in the region in which it was formed. The reaction sequence is unidirectional, i.e., no reactions are permitted that result in the return of tracer to an antecedent substrate. Each substrate has its own unique parameters for permeabilities, reaction rates, and volumes of distribution. The model is useful for analyzing data from tracer glucose, thymidine, adenosine, and fatty acids. Simulations with the model illustrate that endothelial and parenchymal cell events can be clearly distinguished and have shown the importance of metabolism in endothelial cells for producing products whose outflow curves have peaks only slightly shifted in time from that of the parent. (Supported by NIH Grant RR1243.)