Nielsen Vance G, Chawla Nikhil, Mangla Dipty, Gomes Sheldon B, Arkebauer Matthew R, Wasko Kimberly A, Sadacharam Kesavan, Vosseller Keith
Department of Anesthesiology, Drexel University College of Medicine, Pennsylvania, USA.
Blood Coagul Fibrinolysis. 2011 Dec;22(8):756-9. doi: 10.1097/MBC.0b013e32834c7412.
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.
一氧化碳释放分子衍生的一氧化碳在体外已被证明，在人血浆和兔血浆中低浓度（100 - 200 μmol/l）时可增强凝血作用。我们试图确定一氧化碳释放分子-2 [二氯二羰基钌（II）二聚体，CORM-2] 是否会通过血栓弹力图改善兔血浆体外凝血，并在体内临床前兔模型中，研究经口灌胃给予氯吡格雷（20 mg/kg）和阿司匹林（10 mg/kg）后，CORM-2对兔耳出血时间的影响。向兔血浆中添加100 μmol/l CORM-2可显著改善凝血。这种促凝作用被血浆预先暴露于一种能将人血浆中的血红素纤维蛋白原转化为高铁血红素纤维蛋白原的试剂所阻断，从而防止一氧化碳结合和凝血增强。氯吡格雷/阿司匹林给药后2 - 3小时，兔耳出血时间为5.8 ± 1.1分钟。静脉注射CORM-2（10 mg/kg；“最佳情况”瞬时浓度279 μmol/l）5分钟后，出血时间显著缩短至2.6 ± 0.6分钟。CORM-2在体外以类似于人血浆的方式增强血浆凝血，在体内也能增强血浆凝血。计划利用该兔模型对CORM-2对凝血病（如肝素或血液稀释介导的）的影响进行额外的临床前研究。
