Effect of a synthetic factor Xa inhibitor, YM-60828, on blood vessel patency in combination with a thrombolytic agent and on blood loss from the operation site in a rat model of arterial thrombosis

• Published in: Thrombosis and haemostasis Vol. 79; no. 4; p. 859
• Main Authors: Kawasaki, T, Sato, K, Hirayama, F, Koshio, H, Taniuchi, Y, Matsumoto, Y
• Format: Journal Article
• Language: English
• Published: Germany 01.04.1998
• Subjects: Animals; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; Anticoagulants - toxicity; Blood Loss, Surgical - prevention & control; Carotid Arteries - drug effects; Carotid Arteries - ultrastructure; Carotid Artery Thrombosis - drug therapy; Carotid Artery Thrombosis - pathology; Drug Evaluation, Preclinical; Hemorrhage - chemically induced; Heparin - pharmacology; Heparin - therapeutic use; Heparin - toxicity; Male; Naphthalenes - pharmacology; Naphthalenes - therapeutic use; Naphthalenes - toxicity; Pipecolic Acids - pharmacology; Pipecolic Acids - therapeutic use; Pipecolic Acids - toxicity; Piperidines - pharmacology; Piperidines - therapeutic use; Piperidines - toxicity; Rats; Recurrence; Reperfusion; Serine Proteinase Inhibitors - pharmacology; Serine Proteinase Inhibitors - therapeutic use; Serine Proteinase Inhibitors - toxicity; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator - pharmacology; Tissue Plasminogen Activator - therapeutic use; Tissue Plasminogen Activator - toxicity
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1615078

We examined the adjunctive effect of a novel factor Xa inhibitor, YM-60828, on vessel patency and blood loss from the operation site after successful thrombolysis with a modified tissue-type plasminogen activator (moPA) in an electrically-induced carotid artery thrombosis model in rats. Five minutes after the induction of occlusive thrombus, a test drug (YM-60828, argatroban, heparin or saline) was administered by i.v. bolus injection followed by continuous infusion. Thrombolysis was induced with moPA by i.v. bolus injection at a dose of 650,000 IU/ kg. YM-60828 at 1 mg/kg i.v. followed by 3 mg/kg/h significantly prevented reocclusion, increased the duration of patency, and improved vessel patency after successful thrombolysis without any significant increase in blood loss from the operation site. Argatroban at 1 mg/kg i.v. followed by 3 mg/kg/h and heparin at 300 U/kg i.v. followed by 150 U/kg/h also significantly improved these parameters, but were accompanied by a significant increase in blood loss. These results suggest that the factor Xa inhibitor YM-60828 may be a potent and useful adjunctive agent with a lower risk of bleeding complications than argatroban and heparin in thrombolytic therapy.