Effects of nucleotides and nucleosides on coagulation
Effects of nucleotides and nucleosides on coagulation
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DOI：
10.1097/mbc.0b013e328338db27
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发表时间：
2010-07-01
影响因子：
1.1
通讯作者：
Rosenmeier, Jaya B.
中科院分区：
文献类型：
--
作者：
Bune, Laurids T.;Thaning, Pia;Rosenmeier, Jaya B.
在包括脓毒症在内的许多病理状况下，包括 ADP、ATP 和三磷酸尿苷 (UTP) 在内的核苷酸在循环中大量排出。脓毒症可导致低血压以及人体凝血和纤溶系统的全身激活，这可能导致弥散性血管内凝血。我们研究了全身输注腺苷、ADP、ATP、UTP 和一氧化氮引起的核苷酸诱导的心血管虚脱是否会影响止血系统，并通过全血血栓弹力图 (TEG) 分析进行评估。十头猪接受了腺苷、ADP、ATP、UTP 或一氧化氮的随机输注，直到平均动脉压降低至模拟脓毒症引起的低血压的基线的约 40%。通过TEG评估输注对止血系统的影响，并测量组织纤溶酶原激活剂和纤溶酶原激活剂抑制剂-1的内皮释放。与其他输注底物相比，ADP 导致最大幅度降低（71.4 至 64.2；P < 0.05），并减小角度，代表血栓形成（75.6 至 66.4；P < 0.05），表明低凝。尽管 t-PA 释放增加（2.1 至 2.7 ng/ml；P < 0.05），纤溶酶原激活剂抑制剂减少（33.9 +/- 10.9-17.8 +/- 4.4 ng/ml；P < 0.05），但当通过 TEG 评估全血时，未发现纤维蛋白溶解增加。通过 TEG 评估，循环 ADP 会诱导低凝，但没有纤维蛋白溶解增加的迹象。这些发现的潜在临床意义应该进一步研究，因为全身排出的 ADP 可能会导致严重脓毒症中观察到的凝血障碍。血液凝固纤维蛋白溶解 21:436-441 (C) 2010 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins。
Nucleotides, including ADP, ATP and uridine triphosphate (UTP), are discharged profusely in the circulation during many pathological conditions including sepsis. Sepsis can cause hypotension and systemic activation of the coagulation and fibrinolytic systems in humans, which may cause disseminated intravascular coagulation. We investigated whether nucleotide-induced cardiovascular collapse as provoked by systemic infusion of adenosine, ADP, ATP, UTP and nitric oxide affected the haemostatic system as assessed by whole blood thromboelastography (TEG) analysis. Ten pigs received a randomized infusion of adenosine, ADP, ATP, UTP or nitric oxide until mean arterial pressure was reduced to approximately 40% of baseline simulating sepsis-induced hypotension. The effect of the infusions on the haemostatic system was evaluated by TEG, and endothelial release of tissue plasminogen activator and plasminogen activator inhibitor-1 was measured. In contrast to the other infused substrates, ADP caused a reduction in maximum amplitude (71.4 to 64.2; P < 0.05), and reduced the angle, representing the thrombus formation (75.6 to 66.4; P < 0.05), indicating hypocoagulation. Despite increases in t-PA release (2.1 to 2.7 ng/ml; P < 0.05) and reductions in plasminogen activator inhibitor (33.9 +/- 10.9-17.8 +/- 4.4 ng/ml; P < 0.05) no increased fibrinolysis was found when whole blood was evaluated by TEG. Circulating ADP induces hypocoagulation without signs of increased fibrinolysis as evaluated by TEG. The potential clinical significance of these findings should be investigated further because ADP discharged systemically may possibly contribute to the coagulopathy observed in severe sepsis. Blood Coagul Fibrinolysis 21:436-441 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.