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Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits
Journal article   Peer reviewed

Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits

Vance G. Nielsen, Nikhil Chawla, Dipty Mangla, Sheldon B. Gomes, Matthew R. Arkebauer, Kimberly A. Wasko, Kesavan Sadacharam and Keith Vosseller
Blood coagulation & fibrinolysis, v 22(8), pp 756-759
01 Dec 2011
PMID: 22008906

Abstract

Hematology Life Sciences & Biomedicine Science & Technology
Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 mu mol/l) in human and rabbit plasma. We sought to determine if carbon monoxide-releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer, CORM-2] would improve coagulation in rabbit plasma in vitro via thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time following administration of clopidogrel (20 mg/kg) with aspirin (10 mg/kg) via gavage. Addition of 100 mu mol/l CORM-2 to rabbit plasma significantly improved coagulation. This procoagulant effect was blocked by pre-exposure of plasma to an agent that converts hemefibrinogen to methemefibrinogen in human plasma, preventing carbon monoxide binding and enhancement of coagulation. Rabbit ear bleeding time was 5.8 +/- 1.1 min 2-3 h after clopidogrel/aspirin administration. Bleeding time significantly decreased to 2.6 +/- 0.6 min, 5 min after administration of CORM-2 (10 mg/kg; 279 mu mol/l 'best-case' instantaneous concentration) intravenously. CORM-2 enhances plasmatic coagulation in a manner similar to that of human plasma in vitro, and plasmatic coagulation is enhanced in vivo by CORM-2 as well. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin or hemodilution mediated) utilizing this rabbit model is planned. Blood Coagul Fibrinolysis 22:756-759 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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