Single-Capillary Large-Molecule Transport

Huxley, Virginia

Abstract

The view of the capillary exchange barrier has progressed from one of a static barrier to a living structure involved in dynamic regulation of gas, water, and solute movements between blood and tissue. Two classical tenets, fundamental to understanding exchange vessel function, will be evaluated in the current proposal via the test of three hypotheses. Tenet ONE: it is held widely that water and hydrophilic solute fluxes are linked; however, we find these fluxes are linked only under limited conditions and are divorced in the presence of plasma. In addition, anionic plasma proteins appear to mimic electrostatic and not steric actions of whole plasma. Two hypotheses focus on the role of plasma in the regulation of microvessel exchange: I: MACROMOLECULES WILL BE EXCLUDED FROM PATHWAYS THAT CARRY WATER WHEN VESSELS ARE PERFUSED WITH PLASMA. II: NEGATIVELY CHARGED PLASMA COMPONENTS WILL CONFER ELECTROSTATIC RESISTANCE TO SOLUTE MOVEMENT. This is an """"""""evolving"""""""" hypothesis. Tenet TWO: it is held widely that capillaries possess similar basal permeability properties. We find 1) basal water conductivity depends on segment location and 2) network behavior is not predicted by segment water properties alone. No comprehensive studies have examined protein transport within a defined network of microvessels. Thus, Hypothesis III states: PRINCIPAL PATHWAYS FOR MACROMOLECULE TRANSFER WILL BE LOCATED IN REGIONS OF THE VASCULAR NETWORK THAT DIFFER FROM THOSE FOR WATER. The hypotheses will be tested using established methods to quantify flux of water and selected protein probes of known size and charge. Transport will be measured in situ microvessels in the mesentery of the decerebrate frog during plasma and modified-plasma perfusion. Microvessel anatomic location, flow pattern, pressure, length and diameter will be recorded. the passive transfer of macromolecules from individual exchange vessel segments and the network organization of microvessels determined fluid balance. These studies will influence our ability to interpret and model single exchange vessel functions and may bridge the discrepancies between data from whole organs with those from single vessels. Clarification of the nature, location and distribution of water and macromolecule pathways will provide the basic information required to initiate clinical strategies for resolution of vascular pathologies including edema, venous congestion and shock.