Summary
The antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick
anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex
(LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls),
rTAP (50 μg/kg/min continuous infusion) or heparin (200 U/kg bolus followed by 2 U/kg/min
continuous infusion) were started 60 min prior to the initiation of LCX coronary artery
electrolytic injury (150 μA continuous anodal current). All 6/6 saline-treated control
animals developed occlusive thrombi at 49.8 ± 13.6 min after the initiation of vessel
injury, and possessed a residual thrombus mass of 20.7 ± 3.3 mg. In the rTAP treatment
group, 4/6 preparations developed occlusive thrombi, but with times to thrombosis
delayed significantly compared to both the saline control as well as to the heparin
treatment group (202.7 ± 28.9 min; p <0.01 to both saline and heparin groups). The
remaining 2 rTAP-treated preparations remained patent despite the continued electrical
stimulation of the coronary vessel for 5 h. Residual thrombus mass in the rTAP treatment
group was reduced markedly compared to the saline control group (4.4 ± 1.0 mg; p <0.01).
Heparin infusion resulted in a modest but statistically insignificant delay in occlusive
LCX coronary artery thrombosis compared to saline controls, with all 6/6 heparin-treated
preparations occluding at 79.7 ± 16.5 min after the initiation of vessel injury. Residual
thrombus mass in heparin-treated animals, however, was reduced compared to saline
controls (9.4 ± 1.4 mg; p <0.01). These results support a pivotal role for fXa in
the process of arterial thrombosis, as well as the feasibility of inhibiting fXa as
an effective strategy for the primary prevention of arterial thrombosis.
