© 1997 American Heart Association, Inc.
Articles |
Effect of Atherosclerosis on Transmural Convection and Arterial Ultrastructure
Implications for Local Intravascular Drug Delivery
From the Department of Physiology, University of Arizona, and B.W. Zweifach Microcirculation Laboratories, Veterans Affairs Medical Center, Tucson, (A.L.B., L.M.W.); Krannert Institute of Cardiology, Indianapolis, Indiana (I.G.P., R.W., K.M.); and Veterans Affairs Medical Center, Indianapolis, Indiana (K.M.).
Correspondence to Ann L. Baldwin, Department of Physiology, College of Medicine, University of Arizona, Tucson, AZ 85724. E-mail A160854{at}ccit.arizona.edu
Abstract Local infusion of agents through perforated
catheters may reduce neointimal formation following
vascular angioplasty. Such treatment will succeed only if the drug is
retained within the arterial intima long enough to promote
repair. Drugs will be dispersed throughout the wall predominantly by
transmural convection instead of diffusion if the Peclet number,
Pe=J(1-
f)/P, is greater than unity, where J is the
transmural fluid flow per unit surface area and f and P
are the reflection and permeability coefficients to the drug,
respectively. Although the targets of local drug delivery will be
atherosclerotic vessels, little is known about the transport properties
of these vessels. Accordingly, we evaluated the effects of
hypercholesterolemia and
atherosclerosis on J per unit pressure (hydraulic
conductance, Lp) and on ultrastructure in femoral arteries.
Measurements were made at 30, 60, and 90 mm Hg in
anesthetized New Zealand white rabbits fed a normal diet (n=6)
and after 3 weeks of lipid feeding (n=19).
Atherosclerosis was induced in six lipid-fed animals by
air desiccation of a femoral artery. Hydraulic conductance was
significantly greater in vessels from
hypercholesterolemic than from normal animals and
decreased with pressure only in hypercholesterolemic
arteries. Atherosclerosis did not augment hydraulic
conductance compared with hypercholesterolemia
alone. Electron microscopic examination demonstrated damaged
endothelium in hypercholesterolemic
arteries and both altered endothelium and less tightly
packed medial tissue, compared with controls, in atherosclerotic
vessels, at least at lower pressures. Peclet numbers for macromolecules
exceeded unity for all three groups of arteries and reached 0.3 to 0.4
for molecules as small as heparin. Thus, convection plays a dominant
role in the distribution of macromolecular agents following local
delivery and may result in their rapid transport to the adventitia in
the femoral artery.
Key Words: rabbits • artery, femoral • hydraulic conductance • hypercholesterolemia • local drug delivery
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