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.
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.
Kawasaki
T
T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. kawasat@yamanouchi.co.jp
Sato
K
K
Hirayama
F
F
Koshio
H
H
Taniuchi
Y
Y
Matsumoto
Y
Y
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001120:Arginine / Q000031:analogs & derivatives; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002339:Carotid Arteries / Q000187:drug effects* / Q000648:ultrastructure; D002341:Carotid Artery Thrombosis / Q000188:drug therapy* / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D010875:Pipecolic Acids / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D012008:Recurrence; D015424:Reperfusion; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D013449:Sulfonamides; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
D000925:Anticoagulants; D009281:Naphthalenes; D010875:Pipecolic Acids; D010880:Piperidines; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C111032:YM 60828; D006493:Heparin; D001120:Arginine; D010959:Tissue Plasminogen Activator; C031942:argatroban