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

Thrombosis and neointimal hyperplasia limit the utility of small-caliber ar tificial vascular grafts. Surface modifications and adjunctive pharmacologi cal therapy might mediate these complications. We examined the mechanisms b y which a model vasoactive compound, heparin, transverses porous graft mate rials and how material modifications alters this drug's transport. The effe ctive permeance of [H-3]heparin was measured after application of a uniform concentration of drug to either the internal or external surface of the gr aft and in the presence or absence of pressure-driven physiologic hydraulic flows. Transgraft permeance was equivalent to these observed in normal art eries and, while enhanced by convection, was mediated in major part by diff usion. Peclet numbers under the Various conditions examined ranged from 0.0 5. to 1.2, indicating that diffusive forces were equal to or exceeded conve ctive forces in governing transmural heparin motion. Heparin traversed the graft even when applied from the outer perivascular surface, against advers e hydraulic flows. Modifications of the grafts that included a yam barrier of spun poly(tetrafluoroethylene) or chemical modification of surface tensi on energy altered permeances as well. A unifying model for interpretation o f these data incorporates the concept of entrapped air and surface tension energy in the graft. These characterizations allow for the design of vascul ar grafts that are optimized for pharmacotherapy to help prolong graft pate ncy,especially in small-caliber vascular beds. (C) 2000 John Wiley & Sons, Inc.