Dyer Mitchell, Haldeman Shannon, Gutierrez Andres, Kohut Lauryn, Sen Gupta Anirban, Neal Matthew D
Department of Surgery, University of Pittsburgh;
Department of Surgery, University of Pittsburgh.
J Vis Exp. 2017 May 21(123):55554. doi: 10.3791/55554.
Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via a liver laceration that results in consistent blood loss, hemodynamic alterations, and survival. Mice undergo a standardized resection of the left-middle lobe of the liver. They are allowed to bleed without mechanical intervention. Hemostatic agents can be administered as pre-treatment or rescue therapy depending on the interest of the investigator. During the time of hemorrhage, real-time hemodynamic monitoring via a left femoral arterial line is performed. Mice are then sacrificed, blood loss is quantified, blood is collected for further analysis, and organs are harvested for analysis of injury. Experimental design is described to allow for simultaneous testing of multiple animals. Liver hemorrhage as a model of uncontrolled hemorrhage exists in the literature, primarily in rat and porcine models. Some of these models utilize hemodynamic monitoring or quantify blood loss but lack consistency. The present model incorporates quantification of blood loss, real-time hemodynamic monitoring in a murine model that offers the advantage of using transgenic lines and a high-throughput mechanism to further investigate the pathophysiologic mechanisms in uncontrolled hemorrhage.
失控性出血是创伤患者可预防死亡的一个重要原因。我们通过肝脏撕裂伤建立了一种失控性出血的小鼠模型，该模型可导致持续失血、血流动力学改变及存活情况。小鼠接受标准化的左中叶肝脏切除术。让它们自然出血而不进行机械干预。根据研究者的兴趣，止血剂可作为预处理或挽救治疗给药。在出血期间，通过左股动脉插管进行实时血流动力学监测。然后处死小鼠，对失血量进行量化，采集血液用于进一步分析，并摘取器官用于损伤分析。实验设计允许同时对多只动物进行测试。肝脏出血作为失控性出血的模型在文献中已有报道，主要存在于大鼠和猪模型中。其中一些模型采用了血流动力学监测或对失血量进行量化，但缺乏一致性。本模型纳入了失血量的量化、小鼠模型中的实时血流动力学监测，该模型具有利用转基因品系和高通量机制进一步研究失控性出血病理生理机制的优势。
