Soerensen K E, Olsen H G, Skovgaard K, Wiinberg B, Nielsen O L, Leifsson P S, Jensen H E, Kristensen A T, Iburg T M
Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Pathology and Wildlife Disease, National Veterinary Institute, Sweden.
J Comp Pathol. 2013 Nov;149(4):463-74. doi: 10.1016/j.jcpa.2013.04.003. Epub 2013 Jun 6.
Sepsis is a common and often fatal complication in human patients in intensive care units. Relevant and well characterized animal models of sepsis may provide valuable information on pathophysiological mechanisms and be a mean of testing new therapeutic strategies. Large animal models of Staphylococcus aureus sepsis are rare, even though S. aureus increasingly affects human patients. Sepsis changes the haemostatic balance and leads to endothelial cell (EC) activation, coagulopathy and, in severe cases, disseminated intravascular coagulation (DIC). The aim of this study was to characterize the haemostatic and vascular alterations in a novel porcine model of severe S. aureus sepsis, investigating whether the changes fulfill the human clinical criteria for DIC. Five pigs were inoculated intravenously with S. aureus and two control animals were sham-inoculated. Blood samples were collected for thromboelastography (TEG) and assessment of plasma-based haemostatic parameters. Tissue was collected for histopathology and reverse transcriptase quantitative real-time polymerase chain reaction for measurement of mRNA encoding EC markers. All infected animals developed DIC; including procoagulant activation represented by hypercoagulable TEG profiles and prolonged clotting time. Histologically, numerous pulmonary thrombi were present in one pig. Inhibitor consumption was represented by decreasing antithrombin levels in infected pigs. Hyaline globules were found in three infected pigs, confirming fibrinolytic activation. EC activation was identified by expression of von Willebrand factor in small vessels together with elevated mRNA encoding activated EC markers. Severe haemostatic and vascular changes fulfilling the human criteria for DIC were therefore seen in all infected pigs. A tendency towards uncompensated DIC was seen in two animals.
脓毒症是重症监护病房中人类患者常见且往往致命的并发症。相关且特征明确的脓毒症动物模型可能为病理生理机制提供有价值的信息，并成为测试新治疗策略的一种手段。尽管金黄色葡萄球菌对人类患者的影响日益增加，但金黄色葡萄球菌脓毒症的大型动物模型却很罕见。脓毒症会改变止血平衡，导致内皮细胞（EC）活化、凝血病，在严重情况下会导致弥散性血管内凝血（DIC）。本研究的目的是在一种新型的严重金黄色葡萄球菌脓毒症猪模型中表征止血和血管改变，研究这些变化是否符合人类DIC的临床标准。五只猪静脉注射金黄色葡萄球菌，两只对照动物进行假注射。采集血样进行血栓弹力图（TEG）检测和基于血浆的止血参数评估。采集组织进行组织病理学检查和逆转录酶定量实时聚合酶链反应，以测量编码EC标志物的mRNA。所有感染动物均发生了DIC；包括以高凝TEG曲线和延长的凝血时间为代表的促凝活化。组织学上，一只猪出现了大量肺血栓。感染猪抗凝血酶水平降低代表抑制剂消耗。在三只感染猪中发现了透明小球，证实了纤溶激活。通过小血管中血管性血友病因子的表达以及编码活化EC标志物的mRNA升高来确定EC活化。因此，在所有感染猪中均观察到符合人类DIC标准的严重止血和血管变化。两只动物出现了失代偿性DIC的趋势。
