Derde Sarah, Thiessen Steven, Goossens Chloë, Dufour Thomas, Van den Berghe Greet, Langouche Lies
Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven.
Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven;
J Vis Exp. 2017 May 2(123):55553. doi: 10.3791/55553.
This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce sepsis with the use of a central venous line for fluids, drugs and nutrient administration to mimic the human clinical setting. Critically ill patients require intensive medical support in order to survive. While the majority of patients will recover within a few days, about a quarter of the patients need prolonged intensive care and are at high risk of dying from non-resolving multiple organ failure. Furthermore, the prolonged phase of critical illness is hallmarked by profound muscle weakness, and endocrine and metabolic changes, of which the pathogenesis is currently incompletely understood. The most widely used animal model in critical care research is the cecal ligation and puncture model to induce sepsis. This is a very reproducible model, with acute inflammatory and hemodynamic changes similar to human sepsis, which is designed to study the acute phase of critical illness. However, this model is hallmarked by a high lethality, which is different from the clinical human situation, and is not developed to study the prolonged phase of critical illness. Therefore, we adapted the technique by placing a central venous catheter in the jugular vein allowing us to administer clinically relevant supportive care, to better mimic the human clinical situation of critical illness. This mouse model requires an extensive surgical procedure and daily intensive care of the animals, but it results in a relevant model of the acute and prolonged phase of critical illness.
本方案描述了一种用于模拟长期危重症的中心静脉置管小鼠模型。我们将盲肠结扎穿刺法诱导脓毒症与使用中心静脉导管进行液体、药物和营养物质输注相结合，以模拟人类临床情况。危重症患者需要重症医疗支持才能存活。虽然大多数患者会在几天内康复，但约四分之一的患者需要长期重症监护，且死于无法缓解的多器官功能衰竭的风险很高。此外，危重症的延长阶段以严重的肌肉无力以及内分泌和代谢变化为特征，其发病机制目前尚不完全清楚。危重症研究中最常用的动物模型是盲肠结扎穿刺模型，用于诱导脓毒症。这是一个非常可重复的模型，具有与人类脓毒症相似的急性炎症和血流动力学变化，旨在研究危重症的急性期。然而，该模型的特点是高致死率，这与临床人类情况不同，并非用于研究危重症的延长阶段。因此，我们通过在颈静脉放置中心静脉导管对该技术进行了改进，使我们能够给予临床相关的支持性治疗，以更好地模拟危重症的人类临床情况。该小鼠模型需要广泛的外科手术和对动物的日常重症护理，但它能产生一个与危重症急性和延长阶段相关的模型。
