Circulation, Vol 84, 232-243, Copyright © 1991 by American Heart Association
IJ Sarembock, SD Gertz, LW Gimple, RM Owen, ER Powers and WC Roberts
BACKGROUND. The effectiveness of balloon angioplasty is limited by a
restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-
hirudin [CGP 39393]) has been found to be highly effective in preventing
acute platelet-rich thrombosis after deep arterial injury as compared with
heparin. METHODS AND RESULTS. This study evaluated the effect of
intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis
after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was
induced by air desiccation endothelial injury followed by a 2% cholesterol
diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second,
10-atm inflations 60 seconds apart), the rabbits received heparin (150
units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions
of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13).
Angiograms performed before and after angioplasty and before death were
analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours
(n = 14) or 28 days (n = 15) after angioplasty. Femoral arteries were fixed
in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal
diameter of the arteries with successful angioplasty (greater than or equal
to 20% increase in luminal diameter) in rabbits treated with heparin (n = 8
arteries) increased from 1.18 +/- 0.29 mm before angioplasty to 1.86 +/-
0.24 mm immediately after angioplasty (p less than 0.001) and decreased to
0.94 +/- 0.69 mm (p = 0.0004) at 28 days after angioplasty. In rabbits
treated with r-hirudin (n = 11 arteries), the mean luminal diameter
increased from 1.14 +/- 0.17 mm before angioplasty to 1.68 +/- 0.20 mm
immediately after angioplasty (p less than 0.001) and decreased to 1.37 +/-
0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in
luminal diameter by angiography was less in the r-hirudin- treated group
than in the heparin-treated group (0.30 +/- 0.33 versus 0.92 +/- 0.61 mm, p
= 0.01). Blinded planimetric analysis of stained histological sections of
the femoral arteries also showed less cross- sectional area narrowing by
plaque in rabbits treated with r-hirudin compared with those treated with
heparin (22 +/- 16% verus 48 +/- 29%, p = 0.01). Both groups had similar
numbers of arteries with histological evidence of balloon-induced plaque
tear (12 of 13 versus 13 of 15). CONCLUSIONS. Rabbits receiving r-hirudin
at the time of experimental balloon angioplasty had significantly less
restenosis by angiography and by quantitative histopathology than rabbits
receiving heparin.
ARTICLES
Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits
University of Virginia Health Sciences Center, Department of Medicine, Charlottesville 22908.
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