Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits.
Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 μmol/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 μmol/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 μmol/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.
Department of Anesthesiology, Drexel University College of Medicine, Pennsylvania, USA. vance.nielsen@drexelmed.edu
Vance G
VG
Nielsen
Nikhil
N
Chawla
Dipty
D
Mangla
Sheldon B
SB
Gomes
Matthew R
MR
Arkebauer
Kimberly A
KA
Wasko
Kesavan
K
Sadacharam
Keith
K
Vosseller
D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism*; D000077144:Clopidogrel; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006470:Hemorrhage / Q000097:blood* / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D010949:Plasma / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013916:Thrombelastography; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
D005343:Fibrinolytic Agents; D009942:Organometallic Compounds; D010975:Platelet Aggregation Inhibitors; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin