Eugene M Renkin. His Many Contributions to Microvascular Research With Examples of How They Inform Current...

Eugene Renkin used simplified uniform models of microvascular exchange units to describe the fundamental functions of the microcirculation: a cylindrical pore to characterize the barriers to exchange of water and solutes; a uniformly perfused capillary to distinguish flow-limited exchange from diffusion-limited exchange; and a membrane with large and small pores to describe macromolecule exchange between blood and lymph. A key idea linking these concepts to microvascular dysfunction is that local blood flows, microvascular pressures, and the permeability of the vascular wall are not uniformly distributed within microvascular beds. Renkin's concept of microvascular clearance of small solute was extended to show how heterogeneity in blood transit times compromised exchange. It was also extended to evaluate the relative contribution of diffusion, convection, and vesicle exchange to microvascular exchange of macromolecules when there is heterogeneity in macromolecule permeability, measured by the presence of large pores. An extension of his analysis to smaller proteins (14-20 KDa) showed that convective transport may limit the diffusion of inflammatory peptides, therapeutic agents, and toxins from the tissue into circulating blood. We include recent examples of the growing understanding of microvascular dysfunction in chronic disease and approaches to modeling heterogeneity in normal and diseased states.