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Thromb Haemost 1995; 74(02): 640-645
DOI: 10.1055/s-0038-1649791
Original Article
Coagulation
Schattauer GmbH Stuttgart

Primary Prevention of Coronary Arterial Thrombosis with the Factor Xa Inhibitor rTAP in a Canine Electrolytic Injury Model

Joseph J Lynch Jr
The Departments of Pharmacology and Cellular and Molecular Biology, Merck Research Laboratories, West Point, PA, USA
,
Gary R Sitko
The Departments of Pharmacology and Cellular and Molecular Biology, Merck Research Laboratories, West Point, PA, USA
,
E Dale Lehman
The Departments of Pharmacology and Cellular and Molecular Biology, Merck Research Laboratories, West Point, PA, USA
,
George P Vlasuk
The Departments of Pharmacology and Cellular and Molecular Biology, Merck Research Laboratories, West Point, PA, USA
› Author Affiliations
Further Information

Publication History

Received 15 November 1994

Accepted after revision 09 March 1995

Publication Date:
06 July 2018 (online)

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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.

 

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