Comparison of methods for local delivery of tissue factor pathway inhibitor to balloon-injured arteries in rabbits.
BACKGROUND
Prolonged intravenous infusions of recombinant tissue factor pathway inhibitor (rTFPI) have been shown to attenuate markedly neointimal formation and stenosis after balloon-induced injury to the carotid arteries in minipigs.


METHODS
Because local delivery of rTFPI to the injury site would be clinically advantageous, we designed this study to compare the local delivery and retention of rTFPI in balloon-injured arteries using three catheter-based systems.


METHODS
Similar amounts (range 3-4.5 mg) of a mixture of 125I-labeled and unlabeled rTFPI were delivered by either passive diffusion at moderate pressure (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/cm2; e-MED, iontophoresis) to balloon-injured carotid arteries in anesthetized rabbits.


RESULTS
Comparable amounts of rTFPI were retained on the injured vessels immediately after delivery (t = 0) with the LocalMed (628 +/- 68 micrograms/g per cm2, n = 4), SciMed (522 +/- 167 micrograms/g per cm2, n = 4), and e-MED (497 +/- 142 micrograms/g per cm2, n = 4) catheters (NS). However, rTFPI was decreased 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 LocalMed groups, respectively, presumably because of redistribution of rTFPI from remote endothelial or perivascular sites. Retention of rTFPI was six to nine times higher for injured compared with non-injured arteries, and persisted for at least 48 h after delivery with the LocalMed catheter.


CONCLUSIONS
Sustained, marked retention of rTFPI delivered locally at the site of balloon-induced arterial injury appears to result from catheter-based systems that use passive diffusion at moderate pressure.
Yang
L Y
LY
Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110, USA.
St Pierre
J
J
Scherrer
D E
DE
Lasala
J M
JM
Walsh
R G
RG
Abendschein
D R
DR
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D020212:Carotid Artery Injuries; D002404:Catheterization; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D008074:Lipoproteins / Q000008:administration & dosage*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D008074:Lipoproteins; D011994:Recombinant Proteins; C051928:lipoprotein-associated coagulation inhibitor