Influence of blood and plasma flow rate on kinetics of serotonin uptake by lungs

Serotonin extraction following a bolus injection of serotonin and a nonpermeating indicator into the pulmonary artery can be evaluated using a model that represents the saturable uptake of serotonin by Michaelis-Menten kinetics. By use of this model Km, Vmax, and a perfusion parameter, alpha, can be determined by multiple linear regression analysis of the time-concentration data. Kinetic and perfusion parameters were obtained using data from isolated dog lung lobes in which plasma flow rate was changed by changing the pump flow rate in blood- or plasma-perfused lobes or by keeping the pump flow rate constant and removing the blood cells. The calculated Vmax was reproducible and flow independent over the range of flow rates used in the study. The calculated Km was more sensitive than Vmax to small variations in experimental data and was independent of flow at flow rates greater than about one-half the normal cardiac output per gram of lung tissue. The perfusion parameter alpha was lower in the plasma-perfused lobes, reflecting more homogeneous perfusion in the absence of cells. The results suggest that this approach will be useful for separating changes in the kinetics of serotonin uptake by endothelial cells from effects of changes in flow and perfusion heterogeneity.