Mechanisms of heparin transport through expanded poly(tetrafluoroethylene) vascular grafts

Thrombosis and neointimal hyperplasia limit the utility of small-caliber artificial vascular grafts. Surface modifications and adjunctive pharmacological therapy might mediate these complications. We examined the mechanisms by which a model vasoactive compound, heparin, transverses porous graft materials and how material modifications alters this drug's transport. The effective permeance of [(3)H]heparin was measured after application of a uniform concentration of drug to either the internal or external surface of the graft and in the presence or absence of pressure-driven physiologic hydraulic flows. Transgraft permeance was equivalent to those observed in normal arteries and, while enhanced by convection, was mediated in major part by diffusion. Peclet numbers under the various conditions examined ranged from 0.05 to 1.2, indicating that diffusive forces were equal to or exceeded convective forces in governing transmural heparin motion. Heparin traversed the graft even when applied from the outer perivascular surface, against adverse hydraulic flows. Modifications of the grafts that included a yarn barrier of spun poly(tetrafluoroethylene) or chemical modification of surface tension energy altered permeances as well. A unifying model for interpretation of these data incorporates the concept of entrapped air and surface tension energy in the graft. These characterizations allow for the design of vascular grafts that are optimized for pharmacotherapy to help prolong graft patency, especially in small-caliber vascular beds.