Circulation, Vol 89, 1262-1271, Copyright © 1994 by American Heart Association
M Ragosta, LW Gimple, SD Gertz, CT Dunwiddie, GP Vlasuk, HL Haber, ER Powers, WC Roberts and IJ Sarembock
BACKGROUND: Balloon angioplasty of atherosclerotic arteries results in
activation of the coagulation cascade. Several coagulation factors,
including factor Xa and thrombin, are mitogenic for vascular smooth muscle
cells in vitro and thus may play a role in restenosis after balloon
angioplasty. Specific inhibition of factor Xa can be achieved with
recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We
hypothesized that inhibition of Xa would limit restenosis after balloon
angioplasty in an atherosclerotic rabbit model. METHODS AND RESULTS: Focal
femoral atherosclerosis was induced by air desiccation injury and a
high-cholesterol diet in 38 New Zealand White rabbits. Recombinant
antistasin (n = 20 arteries) or rTAP (n = 14 arteries) was administered by
intravenous bolus at the time of balloon angioplasty and followed by a
2-hour infusion; controls (n = 21 arteries) received bolus heparin alone
(150 U/kg). Therapeutic prolongation of the activated partial
thromboplastin time occurred, and antithrombotic drug levels were achieved
in all animals. Luminal diameter in millimeters by quantitative angiography
did not differ between treatment groups before (1.1 +/- 0.2 for controls,
1.1 +/- 0.2 for rATS, and 1.1 +/- 0.3 for rTAP) or after balloon
angioplasty (1.5 +/- 0.3 for controls, 1.4 +/- 0.2 for rATS, and 1.4 +/-
0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to
result in arteries with larger luminal diameter than controls (1.2 +/- 0.3
for rATS, 1.2 +/- 0.3 for rTAP versus 1.0 +/- 0.3 for control, P = .09 by
one-way ANOVA). Restenosis, defined as reduction in angiographic luminal
diameter (in mm) from 2 hours after angioplasty to 28 days after
angioplasty was less in the rATS group than in controls (-0.2 +/- 0.1
versus -0.5 +/- 0.4, P < .001) and tended to be less in the rTAP group
(-0.3 +/- 0.2 versus -0.5 +/- 0.4, P = .07). Quantitative histopathological
analysis showed less percent cross-sectional area narrowing by plaque in
both rATS- and rTAP-treated arteries compared with controls (42 +/- 21%, 47
+/- 18%, and 63 +/- 14%, respectively; P < .01 by one-way ANOVA).
CONCLUSIONS: We conclude that a 2-hour infusion of rATS or rTAP reduced
angiographic restenosis and resulted in less luminal cross-sectional
narrowing by plaque compared with controls.
ARTICLES
Specific factor Xa inhibition reduces restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits
Cardiovascular Division, University of Virginia School of Medicine, Charlottesville 22908.
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