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Carbon monoxide-releasing molecule-2 decreases fibrinolysis in vitro and in vivo in the rabbit
Journal article   Open access   Peer reviewed

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 and Keith Vosseller
Blood coagulation & fibrinolysis, v 23(1), pp 104-107
01 Jan 2012
PMID: 22143252
url
https://doi.org/10.1097/mbc.0b013e32834ea012View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Hematology Life Sciences & Biomedicine Science & Technology
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 (100-200 mu mol/l) in human and rabbit plasma, whereas in vivo administration of large concentrations (>1400 mu mol/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 (1 mg/kg). Addition of 200, 400 and 600 mu mol/l CORM-2 to whole blood significantly improved coagulation and attenuated fibrinolysis compared with blood without CORM-2. Rabbits administered CORM-2 (10 mg/kg, 279 mu mol/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. Blood Coagul Fibrinolysis 23:104-107 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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