Ly. Yang et al., Comparison of methods for local delivery of tissue factor pathway inhibitor to balloon-injured arteries in rabbits, CORON ART D, 10(5), 1999, pp. 327-333
Background Prolonged intravenous infusions of recombinant tissue factor pat
hway inhibitor (rTFPI) have been shown to attenuate markedly neointimal for
mation and stenosis after balloon-induced injury to the carotid arteries in
minipigs.
Design Because local delivery of rTFPI to the injury site would be clinical
ly advantageous, we designed this study to compare the local delivery and r
etention of rTFPI in balloon-injured arteries using three catheter-based sy
stems.
Methods Similar amounts (range 3-4.5 mg) of a mixture of I-125-labeled and
unlabeled rTFPI were delivered by either passive diffusion at moderate pres
sure (5 x 10(5) Pa with the LocalMed InfusaSleeve, or 4 x 10(5) Pa with the
SciMed Dispatch device), or facilitated diffusion combining lower pressure
(2 x 10(5) Pa) and electrical current (3.5 mA/cm(2); e(-)MED, iontophoresi
s) to balloon-injured carotid arteries in anesthetized rabbits,
Results Comparable amounts of rTFPI were retained on the injured vessels im
mediately after delivery (t = 0) with the LocalMed (628 +/- 68 mu g/g per c
m(2), n = 4), SciMed (522 +/- 1 67 mu g/g per cm(2), n = 4), and e(-)MED (4
97 +/- 142 mu g/g per cm(2), n = 4) catheters (NS), However, rTFPI was decr
eased by 37% after 24 h compared with t = 0 (P < 0.02) in the e(-)MED group
, but was increased 1.5-fold (P = 0.02) and 1.3-fold in the SciMed and Loca
lMed groups, respectively presumably because of redistribution of rTFPI fro
m remote endothelial or perivascular sites, Retention of rTFPI was six to n
ine times higher for injured compared with non-injured arteries, and persis
ted for at least 48 h after delivery with the LocalMed catheter.
Conclusions Sustained, marked retention of rTFPI delivered locally at the s
ite of balloon-induced arterial injury appears to result from catheter-base
d systems that use passive diffusion at moderate pressure. Coronary Artery
Dis 10:327-333 (C) 1999 Lippincott Williams & Wilkins.