Blood-tissue exchange via transport and transformation by capillary endothelial cells

The escape of solutes from the blood during passage along capillaries in heart and skeletal muscle occurs via diffusion through clefts between endothelial cells and, for some solutes, via adsorption to or transport across the luminal plasmalemma of the endothelial cell. To quantitate the rates of permeation via these two routes of transport across capillary wall, we have developed a linear model for transendothelial transport and illustrated its suitability for the design and analysis of multiple simultaneous indicator dilution curves from an organ. Data should be obtained for at least three solutes: 1) an intravascular reference, albumin; 2) a solute transported by endothelial cells; and 3) another reference solute, of the same molecular size as solute 2, which neither binds nor traverses cell membranes. The capillary-tissue convection-permeation model is spatially distributed and accounts for axial variation in concentrations, transport through and around endothelial cells, accumulation and consumption within them, exchange with the interstitium and parenchymal cells, and heterogeneity of regional flows. The upslope of the dilution curves is highly sensitive to unidirectional rate of loss at the luminal endothelial surface. There is less sensitivity to transport across the antiluminal surface, except when endothelial retention is low. The model is useful for receptor kinetics using tracers during steady-state conditions and allows distinction between equilibrium binding and reaction rate limitations. Uptake rates at the luminal surface are readily estimated by fitting the model to the experimental dilution curves. For adenosine and fatty acids, endothelial transport accounts for 30-99% of the transcapillary extraction.