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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.

Abstract
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.
AuthorsT Kawasaki, K Sato, F Hirayama, H Koshio, Y Taniuchi, Y Matsumoto
JournalThrombosis and haemostasis (Thromb Haemost) Vol. 79 Issue 4 Pg. 859-64 (Apr 1998) ISSN: 0340-6245 [Print] Germany
PMID9569205 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anticoagulants
  • Naphthalenes
  • Pipecolic Acids
  • Piperidines
  • Serine Proteinase Inhibitors
  • Sulfonamides
  • YM 60828
  • Heparin
  • Arginine
  • Tissue Plasminogen Activator
  • argatroban
Topics
  • Animals
  • Anticoagulants (pharmacology, therapeutic use, toxicity)
  • Arginine (analogs & derivatives)
  • Blood Loss, Surgical (prevention & control)
  • Carotid Arteries (drug effects, ultrastructure)
  • Carotid Artery Thrombosis (drug therapy, pathology)
  • Drug Evaluation, Preclinical
  • Hemorrhage (chemically induced)
  • Heparin (pharmacology, therapeutic use, toxicity)
  • Male
  • Naphthalenes (pharmacology, therapeutic use, toxicity)
  • Pipecolic Acids (pharmacology, therapeutic use, toxicity)
  • Piperidines (pharmacology, therapeutic use, toxicity)
  • Rats
  • Recurrence
  • Reperfusion
  • Serine Proteinase Inhibitors (pharmacology, therapeutic use, toxicity)
  • Sulfonamides
  • Thrombolytic Therapy
  • Time Factors
  • Tissue Plasminogen Activator (pharmacology, therapeutic use, toxicity)

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