Indicator dilution estimation of capillary endothelial transport

Abstract

Mechanisms of transport of substrates and small solutes across the endothelial lining of the capillaries include passive diffusion (through clefts between cells or across the plasmalemma) and transporter-mediated flux across the plasmalemma. Because the transport rates are typically high, the multiple indicator dilution technique is usually the method of choice, as it provides the high temporal resolution required. In the simplest version of this technique, a test solute is injected into the inflow simultaneously with reference solutes that are restricted to intravascular and extracellular space. Interpretation of the resulting data requires models; the most precise approach is to fit the model solutions to the data. When appropriate combinations of indicators and sufficiently complex models (those that account for flow heterogeneity, arteriovenous gradients, passive and saturable transport, reaction, and diffusion in multicomponent systems) are used the transporters can be characterized. Features such as the rapidity of intracellular reaction can also be revealed by this technique.

Figure 1

Outflow dilution curves from dog hindlimb skeletal muscle following injection into the femoral arterial inflow. The ordinate is the fraction of the injected dose emerging per second. The indicators were ¹²⁵I-albumin (intravascular reference), ³H-araH (arabinofuranosylhypoxanthine, extracellular reference) and ¹⁴C-adenosine (the “test solute”). The symbols are the data; ¹⁴C-labelled metabolites of adenosine have been separated in each sample, but are not shown. The smooth curves are model solutions, using a model composed of an aggregate of 4-region units (capillary, endothelial cell, ISF, parenchymal cell) in parallel to account for the measured distribution of regional flows.