Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
Thromb Haemost. 2011 Jan;105(1):145-53. doi: 10.1160/TH10-03-0153. Epub 2010 Nov 5.
During sepsis, the balance between abundantly secreted von Willebrand factor (VWF) and the activity of its size regulating protease ADAMTS13 is assumed to be involved in coagulation abnormalities. We aimed to establish a porcine model with haemorrhagic shock with consecutive sepsis and hypothesised that a decreased ADAMTS13-activity as well as an altered VWF multimer pattern is associated with renal failure. Animals (n=21) were subjected to haemorrhagic shock. After volume replacement, intraperitoneal Escherichia coli sepsis was induced. Blood samples were drawn at baseline, after haemorrhage and sepsis induction. Directly postmortem we examined renal tissue by JONES-silver, CD61, VWF and fibrin staining for characterisation of thrombi. Renal failure was analysed by scoring PAS-stained sections for acute tubular damage. Glomerular microthrombi were observed in six of 21 septic animals. Porcine ADAMTS13 activity declined significantly during sepsis, accompanied by a drop-off in platelet count. At 12 hours after sepsis induction, ADAMTS13 activity was significantly diminished compared to sham controls, and an elevated acute tubular damage score was associated with an increased proportion of high-molecular-weight VWF multimers. Compared to baseline the proportion of high-molecular-weight VWF multimers increased significantly in septic animals. Similar to human sepsis, diminished ADAMTS13 activity was observed in a septic porcine model associated with a shift to rather thrombogenic VWF multimers and deposition of microthrombi. Therefore, this porcine model seems to be appropriate for performing functional and therapeutic studies in sepsis-associated ADAMTS13 deficiency.
在脓毒症中，大量分泌的血管性血友病因子 (VWF) 与调节其大小的蛋白酶 ADAMTS13 的活性之间的平衡被认为与凝血异常有关。我们旨在建立一个伴有出血性休克、继发出血性休克和败血症的猪模型，并假设 ADAMTS13 活性降低以及 VWF 多聚体模式改变与肾衰竭有关。动物（n=21）接受了出血性休克。容量补充后，腹腔内注射大肠杆菌引发败血症。在基线、出血和败血症诱导后采集血样。直接死后，我们通过 JONES 银、CD61、VWF 和纤维蛋白染色检查肾组织，以表征血栓。通过对急性肾小管损伤进行 PAS 染色评分来分析肾衰竭。在 21 例败血症动物中有 6 例观察到肾小球微血栓。猪 ADAMTS13 活性在败血症期间显著下降，同时血小板计数下降。在败血症诱导后 12 小时，ADAMTS13 活性与假手术对照相比显著降低，并且急性肾小管损伤评分升高与高分子量 VWF 多聚体比例增加相关。与基线相比，败血症动物的高分子量 VWF 多聚体比例显著增加。与人类败血症类似，在与 ADAMTS13 缺乏相关的败血症猪模型中观察到 ADAMTS13 活性降低，同时出现向更具血栓形成倾向的 VWF 多聚体转移和微血栓沉积。因此，这种猪模型似乎适合在与败血症相关的 ADAMTS13 缺乏症中进行功能和治疗研究。
