Arterial thrombin activity after angioplasty in an atherosclerotic rabbit model: time course and effect of hirudin.
BACKGROUND
A 2-hour infusion of the direct thrombin inhibitor hirudin at the time of balloon angioplasty limits restenosis in the focally atherosclerotic rabbit. Although short-term administration of hirudin may have a prolonged biological effect, the effect of hirudin on vessel thrombin activity has not been previously studied in an animal model of angioplasty. We hypothesized that a short intravenous infusion of hirudin would result in prolonged inhibition of arterial wall-associated thrombin activity (ATA) after angioplasty.


RESULTS
Sixty-one rabbits received recombinant hirudin (r-hirudin)(1 mg/kg bolus plus 1 mg x kg(-1) x h(-1)x2hours) or bolus heparin (controls, 150 U/kg) intravenously at the time of femoral balloon angioplasty. ATA was measured through exposure of arterial segments ex vivo to fibrinogen and conducting an assay for fibrinopeptide A (FPA). ATA was low in nonballooned, atherosclerotic vessels (FPA=0.5+/-0.3 ng x mL(-1) x mg(-1)) but increased significantly at 24 hours after angioplasty in the heparin group (3.7+/-0.9 ng x mL(-1) x mg(-1), P<.01 versus baseline, n=9) but not in the hirudin group (FPA = 1.4+/-0.3; P=NS versus baseline, P<.02 versus heparin controls, n=8). The time course of ATA after angioplasty was assessed in 44 rabbits. Thrombin activity peaked at 48 hours and declined to baseline at 72 hours and 7 days. FPA values between the heparin and r-hirudin groups were similar at these later time points.


CONCLUSIONS
A 2-hour intravenous infusion of r-hirudin suppressed ATA measured 24 hours after angioplasty in the focally atherosclerotic rabbit. This prolonged biological effect may account, in part, for the reduction in restenosis seen in this model.
Barry
W L
WL
Cardiovascular Division, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Gimple
L W
LW
Humphries
J E
JE
Powers
E R
ER
McCoy
K W
KW
Sanders
J M
JM
Owens
G K
GK
Sarembock
I J
IJ
D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology*; D008297:Male; D010314:Partial Thromboplastin Time; D011184:Postoperative Period; D011817:Rabbits; D011994:Recombinant Proteins; D013917:Thrombin / Q000378:metabolism*; D013997:Time Factors
D006629:Hirudins; D011994:Recombinant Proteins; D013917:Thrombin