Carbon monoxide-releasing molecule-2 decreases fibrinolysis in vitro and in vivo in the rabbit

Vance G. Nielsen, Matthew R. Arkebauer, Kimberly A. Wasko, Saninuj N. Malayaman, Keith Vosseller

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Administration of carbon monoxide derived from carbon monoxide-releasing molecules (CORMs) have been demonstrated to enhance coagulation and diminish fibrinolysis in vitro at small concentrations (100-200μmol/l) in human and rabbit plasma, whereas in vivo administration of large concentrations (>1400μmol/l) of carbon monoxide has mildly increased bleeding time in vivo in rats. We sought to determine whether CORM-2 [tricarbonyldichlororuthenium (II) dimer] would improve coagulation and attenuate tissue-type plasminogen activator (tPA)-mediated fibrinolysis in rabbit whole blood as determined in vitro by thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time administered intravenous tPA (1mg/kg). Addition of 200, 400 and 600μmol/l CORM-2 to whole blood significantly improved coagulation and attenuated fibrinolysis compared with blood without CORM-2. Rabbits administered CORM-2 (10mg/kg, 279μmol/l) had a small but significant decrease in bleeding time before tPA administration. Administration of tPA resulted in bleeding times more than six-fold greater than baseline in animals not exposed to CORM-2, whereas rabbits administered CORM-2 had significantly smaller (more than five-fold less) bleeding time values after tPA administration. CORM-2 administration significantly decreases fibrinolytic bleeding in the rabbit in vivo. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin-mediated or clopidogrel- mediated) utilizing this rabbit model are planned.

Original languageEnglish (US)
Pages (from-to)104-107
Number of pages4
JournalBlood Coagulation and Fibrinolysis
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Keywords

  • bleeding time
  • carbon monoxide-releasing molecule
  • fibrinolysis
  • rabbit
  • thrombelastography

ASJC Scopus subject areas

  • Hematology

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