ym-60828 and Blood-Loss--Surgical

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.

Topics: Animals; Anticoagulants; Arginine; Blood Loss, Surgical; Carotid Arteries; Carotid Artery Thrombosis; Drug Evaluation, Preclinical; Hemorrhage; Heparin; Male; Naphthalenes; Pipecolic Acids; Piperidines; Rats; Recurrence; Reperfusion; Serine Proteinase Inhibitors; Sulfonamides; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator