Kinetics of uptake and metabolism by endothelial cell from indicator dilution data

Certain substrates are rapidly taken up and/or metabolized by pulmonary endothelial cells in a saturable process. When such a substrate and a reference indicator are included in a bolus which is injected into the blood flowing into the lung, the extraction ratio, E(t), curves measured in the pulmonary venous outflow are asymmetric with respect to the reference indicator curve. If a sufficient quantity of substrate is included in the bolus, the extraction curves are concave upward. The shapes of the E(t) curves contain information regarding the chemical-physical processes which govern the fate of the substrate during its single passage through the lung. To interpret the shapes, computer simulations are used to illustrate separately the effects of the uptake of substrate into the cell, the returning flux of the substrate from the cell, the saturation phenomena of the extraction process, and the perfusion heterogeneity of the capillaries. Lastly, a simple analytical method for estimating the organ kinetic parameters of the extraction process is presented.