Name: uncontrolled hemorrhagic shock modeled via liver laceration in mice with real time hemodynamic monitoring
Uploaded: 2017-05-21T13:00:00
Description: Watch this Scientific Journal Video about Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring at JoVE.com

该手稿的工作得到了血液医学研究所止血和血管生物学（P3HVB）试验项目计划和AAST研究奖学金资助Neal博士的支持。这项工作得到美国国家卫生研究院授权1 R35 GM119526-01和UM1HL120877-01的支持。

根据匹兹堡大学（美国宾夕法尼亚州匹兹堡）和美国国家卫生研究院（NIH; Bethesda，MD，美国）的动物护理指南，在特定无病原体条件下，12小时光暗循环并自由进入小鼠标准饲料和水。所有动物实验均按照匹兹堡大学动物研究和监督委员会制定的指导方针进行了批准和实施。 手术场和仪器设置<ol><li> 在手术之前，将所有手术器械，缝合线，纱布，棉尖涂抹器，管道和?...

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	<li>Chang, R., Cardenas, J. C., Wade, C. E., Holcomb, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+the+understanding+of+trauma-induced+coagulopathy.">Advances in the understanding of trauma-induced coagulopathy.</a> Blood. 128 (8), 1043-1049 (2016).</li><li>Kutcher, M. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+paradigm+shift+in+trauma+resuscitation:+evaluation+of+evolving+massive+transfusion+practices.">A paradigm shift in trauma resuscitation: evaluation of evolving massive transfusion practices.</a> JAMA surgery. 148 (9), 834-840 (2013).</li><li>Tsukamoto, T., Pape, H. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+Models+for+Trauma+Research.">Animal Models for Trauma Research.</a> Shock. 31 (1), 3-10 (2009).</li><li>Darwiche, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pseudofracture:+an+acute+peripheral+tissue+trauma+model.">Pseudofracture: an acute peripheral tissue trauma model.</a> J Vis Exp. (50), (2011).</li><li>Lomas-Niera, J. L., Perl, M., Chung, C. -. S., Ayala, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Shock+and+Hemorrhage:+an+Overview+of+Animal+Models.">Shock and Hemorrhage: an Overview of Animal Models.</a> Shock. 24, 33-39 (2005).</li><li>Kohut, L. K., Darwiche, S. S., Brumfield, J. M., Frank, A. M., Billiar, T. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fixed+volume+or+fixed+pressure:+a+murine+model+of+hemorrhagic+shock.">Fixed volume or fixed pressure: a murine model of hemorrhagic shock.</a> J Vis Exp. (52), (2011).</li><li>Matsuoka, T., Hildreth, J., Wisner, D. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liver+injury+as+a+model+of+uncontrolled+hemorrhagic+shock:+resuscitation+with+different+hypertonic+regimens.">Liver injury as a model of uncontrolled hemorrhagic shock: resuscitation with different hypertonic regimens.</a> J Trauma. 39 (4), 674-680 (1995).</li><li>Komachi, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adhesive+and+Robust+Multilayered+Poly(lactic+acid)+Nanosheets+for+Hemostatic+Dressing+in+Liver+Injury+Model.">Adhesive and Robust Multilayered Poly(lactic acid) Nanosheets for Hemostatic Dressing in Liver Injury Model.</a> J. Biomed. Mater. Res. Part B Appl. Biomater. , (2016).</li><li>Orfanos, N. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effects+of+antioxidants+on+a+porcine+model+of+liver+hemorrhage.">The effects of antioxidants on a porcine model of liver hemorrhage.</a> J Trauma Acute Care Surg. 80 (6), 964-971 (2016).</li><li>Morgan, C. E., Prakash, V. S., Vercammen, J. M., Pritts, T., Kibbe, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+validation+of+4+different+rat+models+of+uncontrolled+hemorrhage.">Development and validation of 4 different rat models of uncontrolled hemorrhage.</a> JAMA Surgery. 150 (4), 316-324 (2015).</li><li>Rosselli, D. D., Brainard, B. M., Schmiedt, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+of+a+topical+bovine-derived+thrombin+solution+as+a+hemostatic+agent+in+a+rodent+model+of+hepatic+injury.">Efficacy of a topical bovine-derived thrombin solution as a hemostatic agent in a rodent model of hepatic injury.</a> Can J Vet Res. 14 (14), 303-308 (2015).</li><li>Sheppard, F. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+Nonhuman+Primate+(Rhesus+Macaque)+Model+of+Uncontrolled+Traumatic+Liver+Hemorrhage.">Development of a Nonhuman Primate (Rhesus Macaque) Model of Uncontrolled Traumatic Liver Hemorrhage.</a> Shock. 44, 114-122 (2015).</li><li>Nemzek-Hamlin, J. A., Hwang, H., Hampel, J. A., Yu, B., Raghavendran, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+murine+model+of+blunt+hepatic+trauma.">Development of a murine model of blunt hepatic trauma.</a> Comp Med. 63 (5), 398-408 (2013).</li><li>Vogel, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Platelet-derived+HMGB1+is+a+critical+mediator+of+thrombosis.">Platelet-derived HMGB1 is a critical mediator of thrombosis.</a> J Clin Invest. 125 (12), (2015).</li><li>Modery-Pawlowski, C. L., Tian, L. L., Ravikumar, M., Wong, T. L., Sen Gupta, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vitro+and+in+vivo+hemostatic+capabilities+of+a+functionally+integrated+platelet-mimetic+liposomal+nanoconstruct.">In vitro and in vivo hemostatic capabilities of a functionally integrated platelet-mimetic liposomal nanoconstruct.</a> Biomaterials. 34 (12), 3031-3041 (2013).</li></ol>

这里描述的鼠肝切除模型提供了可靠，一致的不受控制的出血模型。这种模式是直接执行的，但是需要仔细考虑的重要步骤。模型中技术上最具挑战性的部分是用于血液动力学监测和流体/药物施用的股骨血管插管。在切除神经和动脉切开术/静脉切开术时必须小心。重要的是在解剖血管期间不要接触神经，以避免造成神经损伤和可能的麻痹，特别是对于生存模型。动脉切开术和静脉切开术需要精?...

创伤是世界各地年轻人死亡和残疾的主要原因。 1严重受伤创伤患者死亡的主要原因是不受控制的出血。 2出血性创伤患者的管理是双重的：手术出血的控制，血液的复苏和更换。 出血性休克的动物模型一直是创伤研究的基石，可用于评估创伤性/出血性休克的病理生理和治疗。 3，4动物模型的冲击可以通过两种方法实现：控制出血和不受控制的出血。 5，6通过去除固定体积的血液或通过除血实现一定血压（固定压力）进行控制性出血。当时se模型在出血性休克的机制和免疫变化的评估中是有用的，它们不适用于止血剂的测试，并且不模拟创伤后出血的临床情况。在这个程度上，我们试图开发一种不受控制的出血模型，这将允许我们在鼠模型中测试止血变化和促凝剂。肝脏是不受控制的出血的有吸引力的选择，部分原因是肝脏双重供血，而且是钝伤和穿透性创伤中最常见的腹内器官损伤之一。鉴于临床相关性很高，肝脏已被用作不受控制的出血模型，最常见于大鼠和猪模型，但最近也在灵长类动物中。 7，8，9，10，11，12 </su小鼠模型也纳入了肝损伤，如粉碎模型或钝性创伤;然而，这些模型不会导致继发于肝损伤的出血性休克。 13，14 不受控制的肝出血的大鼠和猪模型虽然在复苏实践和血液动力学监测方面有价值，但是由于各种原因（例如成本，使用动物数量）和重要的是相对缺乏可用于分析的转基因品系的特异性细胞和分子信号。目前的鼠模型与现有的肝脏出血模型具有重要的相似之处，包括标准化肝脏撕裂，失血量化，血液动力学监测和进行生存分析的能力。许多现有的模型只包括这些方面的一些，而我们的模型被开发用于测量许多生理变异同时和在多个小鼠。同样，鼠模型的发展打开了复苏之外的调查之门，并在不受控制的出血中形成更大的病理生理机制，具有使用先进分子技术的成本效益高，高通量模型的潜力。

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			<td>30G needle</td>
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			<td>10cc syringe</td>
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			<td>50cc conical tube</td>
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			<td>1cc syringe w/ 25G needle</td>
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			<td>Fisher Scientific</td>
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			<td>surgical blue pad</td>
			<td>Fisher Scientific</td>
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			<td>Sterile Field dressings</td>
			<td>Fisher Scientific</td>
			<td>NC9517505</td>
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			<td>tape rolls 1&#34;</td>
			<td>Corporate Express</td>
			<td>MMM26001</td>
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			<td>straight side wide mouth jars</td>
			<td>VWR</td>
			<td>159000-058</td>
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			<td>stainless steel tray 8&#34; x 11&#34;</td>
			<td>VWR</td>
			<td>62687-049</td>
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			<td>male-male leur lock 3-way</td>
			<td>VWR</td>
			<td>20068-909</td>
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			<td>sterilization pouch 3&#34;x8&#34;</td>
			<td>VWR</td>
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			<td>sterilization pouch 5&#34;x10&#34;</td>
			<td>VWR</td>
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			<td>absorption triangles</td>
			<td>Fine Science Tools</td>
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			<td>7mm wound clip applier</td>
			<td>Fisher Scientific</td>
			<td>E0522687</td>
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			<td>1000 7mm wound clips</td>
			<td>Fisher Scientific</td>
			<td>E0522687</td>
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			<td>betadine (4oz)</td>
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			<td>Fisher Scientific</td>
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			<td>small weigh boat</td>
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			<td>lactated ringers</td>
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			<td>hepranized saline solution (.1&#181; hep + 9.9&#181;NaCl)</td>
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			<td>phosphate buffered saline&#160;</td>
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			<td>pentobarbital&#160;</td>
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			<td>Wild M650 microscope w/ boom stand</td>
			<td>Leica</td>
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			<td>Digi-Med BPA-400 analyzer &#38; systems integrator</td>
			<td>Micro-Med</td>
			<td>SYS-400</td>
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			<td>TXD-310 (Digi-Med Transducer)&#160;</td>
			<td>Micro-Med</td>
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			<td>Computer</td>
			<td>Dell</td>
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			<td>microbead instrument sterilizer</td>
			<td>VWR</td>
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			<td>Oster A5 clippers w. size 40 blade</td>
			<td>VWR</td>
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			<td>circulating heating pad 18x26</td>
			<td>Harvard</td>
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			<td>rectal thermometer</td>
			<td>Kent Scientific</td>
			<td>RET-3</td>
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uncontrolled hemorrhagic shock modeled via liver laceration in mice with real time hemodynamic monitoring

不受控制的出血是创伤患者可预防死亡的重要原因。我们已经通过肝切除开发了一种不受控制的出血的鼠模型，导致持续的失血，血液动力学改变和存活。 小鼠进行肝左中叶的标准化切除。他们被允许出血而没有机械干预。根据研究者的兴趣，止血剂可以作为预处理或拯救治疗来施用。在出血期间，通过左股动脉线进行实时血流动力学监测。然后处死小鼠，量化血液损失，收集血液进行进一步分析，收集器官用于分析损伤。描述了实验设计，以允许同时测试多只动物。 肝出血作为不受控制的出血的模型存在我在文献中，主要在大鼠和猪模型中。这些模型中的一些使用血液动力学监测或量化失血，但缺乏一致性。本模型结合了在鼠模型中的失血定量，实时血液动力学监测，其提供使用转基因品系的优点和高通量机制来进一步研究不受控制的出血的病理生理机制。

肝脏撕裂模型导致小鼠可重复且一致的失血。 图1A示出了可以获得的撕裂肝脏的一致重量，其标准偏差仅为0.02g。撕裂肝脏重量的这种一致性允许在小鼠之间和不同的实验装置中再现模型的能力，例如不同的复苏方案。同样，撕裂肝脏的可重复重量的标准误差仅为0.01g，为动物模型中难以获得的不受控制的出血提供更标准的模型。 <p class="jove_content" fo:keep-tog...

Watch this Scientific Journal Video about Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring at JoVE.com

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

不可控的出血是创伤患者死亡的重要原因，可以使用鼠模型中的标准肝脏撕裂进行建模。该模型导致失血，存活的一致性，并允许测试止血剂。本文提供了执行此有价值模型的分步过程。

通过实时血液动力学监测在小鼠中通过肝脏浸润建立的不受控制的出血性休克

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via ...

Research

JoVE Journal

Medicine

Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

固定体积或固定压力：失血性休克的小鼠模型

It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. 1, ...

科研

医学

Controlled Cervical Laceration Injury in Mice

控制宫颈裂伤损伤小鼠

Use of genetically modified mice enhances our  understanding of molecular mechanisms underlying several neurological disorders  such as a spinal cord ...

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

全身及肝脏血流动力学参数的监测小鼠

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. ...

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

小鼠急性心肌梗死的实时压力容积分析

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...

Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine

完全性和部分主动脉闭塞治疗猪失血性休克

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the ...

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy

肝静脉压梯度和转性肝活检测量

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced ...

Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs

由脑氧测量和猪期扩展血液动力学监测指导的标准化出血性休克诱导

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an ...

Real-Time Monitoring of Neurocritical Patients with Diffuse Optical Spectroscopies

使用漫反射光谱实时监测神经危重症患者

Neurophysiological monitoring is an important goal in the treatment of neurocritical patients, as it may prevent secondary damage and directly impact ...

Organ Ischemia-Reperfusion Injury by Simulating Hemodynamic Changes in Rat Liver Transplant Model

器官缺血-输液损伤模拟大鼠肝脏移植模型的血动力学变化

Orthotopic liver transplantation (OLT) in rats is a tried and proven animal model used for preoperative, intraoperative, and postoperative studies, ...

Complete and Partial Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhagic Shock

完全和部分复苏性主动脉血管内球囊闭塞治疗出血性休克

Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for ...