title: The antifibrinolytic effects of carbon monoxide-releasing molecule-2 are fibrin and alpha2-antiplasmin dependent.
abstract: Carbon monoxide derived from a carbon monoxide-releasing molecule [tricarbonyldichlororuthenium (II) dimer; CORM-2] has been recently demonstrated to diminish tissue-type plasminogen activator (tPA)-mediated fibrinolysis of plasma thrombi via enhancement of alpha2-antiplasmin-plasmin interactions. The goal of this study was to confirm this mechanism by comparing tPA-mediated fibrinolysis with fibrin-independent, alpha2-antiplasmin-resistant streptokinase-mediated fibrinolysis in CORM-2 exposed plasma. Normal plasma was exposed to 0 or 100 micromol/l CORM-2, with coagulation activated with tissue factor and fibrinolysis initiated with 100 U/ml tPA or 50 U/ml streptokinase. Thrombus growth/disintegration kinetics were monitored with thrombelastography until clot lysis time occurred. Unlike tPA-lysed clots, streptokinase-exposed thrombi demonstrated no significant CORM-2-mediated prolongation of clot growth time or clot lysis time. In contrast, streptokinase-mediated lysis did not significantly change the CORM-2-mediated percentage increase in the maximum rate of clot growth or maximum rate of clot lysis compared with tPA-exposed thrombi. CORM-2 likely attenuates fibrinolysis by a fibrin-dependent/alpha2-antiplasmin-dependent mechanism. Additional molecular investigation (e.g., mass spectroscopy) is planned to further elucidate how CORM-2 modifies fibrinogen/fibrin.
authors.affiliation: Department of Anesthesiology, Drexel University College of Medicine, Broad & Vine Streets, Philadelphia, PA 19102, USA. vance.nielsen@drexelmed.edu
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
mesh_terms: D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002248:Carbon Monoxide / Q000494:pharmacology*; D005337:Fibrin / Q000502:physiology*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology; D013300:Streptokinase / Q000494:pharmacology; D013916:Thrombelastography; D013925:Thromboplastin; D013927:Thrombosis / Q000209:etiology; D010959:Tissue Plasminogen Activator; D000979:alpha-2-Antiplasmin / Q000502:physiology*
chemical_list: D000933:Antifibrinolytic Agents; D009942:Organometallic Compounds; D000979:alpha-2-Antiplasmin; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D005337:Fibrin; D013925:Thromboplastin; D013300:Streptokinase; D010959:Tissue Plasminogen Activator