King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Crit Care Med. 2012 Apr;40(4):1229-36. doi: 10.1097/CCM.0b013e3182387bef.
Excessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses.
Randomized controlled study.
Comparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Baboons (Papio Hamadryas).
Twelve anesthetized baboons assigned randomly to recombinant nematode anticoagulant protein c2, a powerful inhibitor of tissue factor/factor VIIa-dependent coagulation (n = 6), or a control group (n = 6) were heat-stressed in a prewarmed neonatal incubator at 44-47°C until systolic blood pressure fell <90 mm Hg, signaling the onset of severe heat stroke. Recombinant nematode anticoagulant protein c2 was administered as a single intravenous dose of 30 μg/kg body weight at onset of heat stroke. The control group received an equivalent volume of sterile saline intravenously.
Heat stroke was associated with coagulation activation and fibrin formation as evidenced by the increased plasma thrombin-antithrombin complexes, endogenous thrombin potential, and D-dimer levels. Recombinant nematode anticoagulant protein c2 induced significant inhibition of thrombin generation and fibrin formation. Inhibition of coagulation in recombinant nematode anticoagulant protein c2-treated animals did not influence either fibrinolysis (assessed by tissue plasminogen activator, plasmin-α2-antiplasmin complexes, and plasminogen activator inhibitor) or the release of pro- and anti-inflammatory cytokines. No difference in markers of cell injury and organ dysfunction was observed between recombinant nematode anticoagulant protein c2-treated and control groups.
Tissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced-heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction.
过度激活凝血，最终导致显性弥散性血管内凝血，是中暑的一个突出特征。然而，引发凝血激活的机制及其致病作用尚不清楚。我们研究了组织因子/因子 VIIa 复合物是否会引发中暑时的凝血激活，如果是这样，通过中和其上游来抑制凝血激活是否可以最大程度地减少细胞损伤和器官功能障碍。我们还研究了凝血抑制是否会影响中暑引起的纤维蛋白溶解和炎症反应。
随机对照研究。
沙特阿拉伯利雅得法赫德国王专科医院比较医学系。
狒狒（Papio hamadryas）。
将 12 只麻醉的狒狒随机分为重组线虫抗凝蛋白 c2 组（n = 6）和对照组（n = 6），将其放置在预热的新生儿保温箱中加热至 44-47°C，直至收缩压降至<90mmHg，表明严重中暑开始。在中暑开始时，重组线虫抗凝蛋白 c2 以 30μg/kg 体重的单次静脉剂量给药。对照组静脉注射等量的无菌生理盐水。
中暑与凝血激活和纤维蛋白形成有关，这表现为血浆凝血酶-抗凝血酶复合物、内源性凝血酶潜能和 D-二聚体水平增加。重组线虫抗凝蛋白 c2 诱导显著抑制凝血酶生成和纤维蛋白形成。重组线虫抗凝蛋白 c2 治疗动物的凝血抑制对纤维蛋白溶解（通过组织纤溶酶原激活物、纤溶酶-α2-抗纤溶酶复合物和纤溶酶原激活物抑制剂评估）或促炎和抗炎细胞因子的释放没有影响。在重组线虫抗凝蛋白 c2 治疗组和对照组之间，未观察到细胞损伤和器官功能障碍标志物的差异。
组织因子/因子 VIIa 依赖性途径在诱导性中暑的狒狒中引发凝血激活，而对纤维蛋白溶解和炎症没有影响。这些发现还表明，凝血激活不是细胞损伤和器官功能障碍的先决条件。
