Arterial heparin deposition: role of diffusion, convection, and extravascular space

Transvascular transport has been studied with atherogenic, tracer, and iner t compounds such as low-density lipoprotein, horseradish peroxidase, and al bumin, respectively. Few studies used vasoactive compounds, and virtually a ll studies examined entry from the lumen and not from the perivascular spac e. We compared several mechanisms that govern arterial heparin deposition a fter administration to the perivascular and endovascular aspects of the cal f carotid artery in vitro and the rabbit iliac artery in vivo. In the absen ce of transmural hydrostatic pressure gradients, heparin deposition followi ng endovascular administration was unaffected by deendothelialization and w as indistinguishable from perivascular delivery. Deposition in the former w as enhanced by the addition of a pressure gradient and to a greater extent in denuded arteries, indicating that convection influences transport but is dampened by the endothelium. Neither the endothelium nor the adventitia po se significant resistances to heparin. Deposition in vivo was greater follo wing endovascular hydrogel release than perivascular application from simil ar devices to native or denuded arteries. The loss of drug to extra-arteria l microvessels exceeded the loss of drug to the lumen flow. These findings are essential for describing vascular pharmacokinetics and for implementing local pharmacotherapies.