title: Carbon monoxide releasing molecule-2 enhances coagulation and attenuates fibrinolysis by two mechanisms: insights gained with colloid dilution.
abstract: Carbon monoxide releasing molecule-2 (CORM-2, tricarbonyldichlororuthenium (II) dimer) enhances coagulation and attenuates vulnerability to fibrinolysis. Our goal was to further define the CORM-2-mediated mechanisms using colloids with known effects on coagulation/fibrinolytic proteins. Plasma diluted 0 or 30% with 0.9% NaCl, 5% human albumin, low molecular weight hydroxyethyl starch (130 kDa) or high molecular weight hydroxyethyl starch (450 kDa) was exposed to 0 or 100 μmol/l CORM-2 before activation with tissue factor (n = 8 per condition). A second identically diluted series of experiments were performed with the addition of tissue-type plasminogen activator. Thrombelastographic data were collected until clot strength stabilized or clot lysis occurred. Dilution resulted in fluid-specific decreases in velocity of clot growth, strength and clot growth time with progressive increases in macromolecule size. CORM-2 exposure significantly increased the velocity of clot formation and strength (thin fibrin fiber promoting), but not clot growth time, under all conditions. Fibrinolysis was enhanced to the greatest extent by hydroxyethyl starch (antiα2-antiplasmin effect), and CORM-2 addition attenuated fibrinolysis in all conditions (α2-antiplasmin enhancement). CORM-2 exposure attenuated the decrease in coagulation kinetics mediated by hemodilution by two different mechanisms based on kinetic profile differences between the diluents tested. Further laboratory-based investigation is warranted to further define the molecular mechanisms responsible for CORM-2-mediated effects on coagulation and fibrinolysis.
authors.affiliation: Department of Anesthesiology, Drexel University College of Medicine, Broad & Vine Streets, Philadelphia, PA 19102, USA.
authors.forename: Jack B
authors.initials: JB
authors.lastname: Cohen
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Persaud
authors.forename: Saninuj N
authors.initials: SN
authors.lastname: Malayaman
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology*; D010952:Plasma Substitutes / Q000494:pharmacology*; D013916:Thrombelastography / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D009942:Organometallic Compounds; D010952:Plasma Substitutes; C447082:tricarbonyldichlororuthenium (II) dimer; D010959:Tissue Plasminogen Activator