Carbon monoxide releasing molecule-2 increases the velocity of thrombus growth and strength in human plasma.
Carbon monoxide derived from degradation of heme by heme oxygenase or carbon monoxide releasing molecules (CORMs) has been demonstrated to decrease thrombosis in vivo and to weakly inhibit platelet aggregation. We tested the hypothesis that carbon monoxide released from tricarbonyldichlororuthenium (II) dimer (CORM-2) would diminish the velocity of formation and strength of plasma thrombi as determined by thrombelastography. Normal plasma was exposed to 0 or 100 micromol/l CORM-2 or inactivated CORM-2 (iCORM-2), with coagulation initiated with tissue factor or celite (n = 8 per condition). Additional experiments utilized factor XIII (FXIII) deficient plasma activated with celite. Coagulation kinetics was monitored with thrombelastography for 15 min. CORM-2, and to a lesser extent, iCORM-2, significantly (P < 0.05) increased the velocity of formation (122 and 56%, respectively) and strength (66 and 57%, respectively) of plasma clots initiated with either tissue factor or celite compared with thrombi not exposed to CORM-2 or iCORM. In FXIII deficient plasma CORM-2 significantly increased the velocity of clot formation (264%) and strength (240%). Carbon monoxide and iCORM-2 derived from CORM-2 markedly enhance the velocity of clot growth and strength. These findings serve as the rationale for further investigations to determine if CORMs could be utilized as hemostatic agents.
Nielsen
Vance G
VG
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA. vgnielsen333@gmail.com
Kirklin
James K
JK
George
James F
JF
D001777:Blood Coagulation / Q000187:drug effects*; D002248:Carbon Monoxide / Q000494:pharmacology; D007692:Diatomaceous Earth / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005177:Factor XIII Deficiency / Q000097:blood; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009942:Organometallic Compounds / Q000494:pharmacology*; D010949:Plasma; D013916:Thrombelastography
D006490:Hemostatics; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D007692:Diatomaceous Earth; D002248:Carbon Monoxide