Primary prevention of coronary arterial thrombosis with the factor Xa inhibitor rTAP in a canine electrolytic injury model.
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 micrograms/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 microA 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Lynch
J J
JJ
Department of Pharmacology, Merck Research Laboratories, West Point, PA, USA.
Sitko
G R
GR
Lehman
E D
ED
Vlasuk
G P
GP
D000818:Animals; D000925:Anticoagulants / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D060829:Arthropod Proteins; D003328:Coronary Thrombosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000293:injuries; D004285:Dogs; D004341:Drug Evaluation; D004572:Electrolysis / Q000009:adverse effects; D065427:Factor Xa Inhibitors; D005240:Feasibility Studies; D005260:Female; D006493:Heparin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008046:Lip / Q000293:injuries; D008297:Male; D006472:Oral Hemorrhage / Q000188:drug therapy; D010455:Peptides / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use
D000925:Anticoagulants; D060829:Arthropod Proteins; D065427:Factor Xa Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011994:Recombinant Proteins; C063967:tick anticoagulant peptide; D006493:Heparin