这项工作是由美国陆军医学研究和装备司令部，作战伤员救护方案提供资金支持。我们感谢LTC凯文S.埃克斯，MD和克里斯汀R.碱液女士为他们制作的视频帮助。

在此之前任何人的过程中，机构审查委员会（IRB）必须批准该协议。在这项研究中使用的协议被批准由美国陆军医学研究和装备司令部IRB。该协议旨在演示在中央血容量逐步减少类似于在受控和可重复的实验室设置持续出血时由个人经历的补偿的生理反应。 25˚C - 实验室房间温度在23控制。 1.设备的准备<ol><li>打开设备并需要预热和校准设备。 注:设备和装置包括一个数据采集系统，记录在1赫兹的数据;这提供了使用两个单独的红外线手指光电容积袖带传感器9-11肱动脉血压和动脉血氧饱和度的非侵入性，连续测量（SPO 2）两个独立的设备;一个capnograpH值呼气末二氧化碳和呼吸频率的测量;和手指脉搏血氧计收购周边动脉搏动波形测量补偿储备。 </li><li>通过调整每个仪器时间戳匹配实验室主时钟将用于在实验过程中以标记时间同步所有与内部时钟的文书。 </li></ol> 2.除准备<ol><li>指示受试者避免咖啡因，酒精和剧烈运动24小时测试之前，并避免食用之前在血液动力学失代偿诱导恶心事件的协议，至少2小时。 </li><li>在此之前的协议开始，有医生进行体检检查，以确保符合题目最低卫生要求，并确保没有排除标准（尼古丁的使用，高血压，植物神经功能紊乱，或晕厥发作史）。由于怀孕是排除标准参与，要求女性参与者采取一个标准的尿妊娠试验在研究的当天。 注:有关主体的安全性，研究医生是高级生命支持认证，并在研究过程中存在。设备齐全的"急救车"可立即支持意识丧失或急性心律失常的LBNP过程中发生的事件中受到的气道，呼吸及循环。 </li><li>告知程序的问题，并取得书面同意参与这项研究。 注:解释给课题研究的目的是应用下体负压直到心血管失代偿（先兆）的发作。解释，有限定这一点心血管参数，并当观察这些心血管参数下体负压将被终止。告知他们也可以体验的症状通常有先兆的LBNP PROCE期间相关的主题杜热。责成主题，如果出现这些症状和下体负压将立即终止通知调查。 </li><li>广场上的主题氯丁橡胶下体负压裙子。确保该裙是为了创造一个气密密封围绕腰部和躯干贴身。 </li><li>责成主题，同时横跨固定后LBNP期间固定在躯干的地方，躺在下体负压室的床上平卧。指示主题LBNP暴露过程中放松下半身。通过滑动床进入室和附加氯丁橡胶裙到室开口以创建一个气密密封固定主体入下体负压室中。 注:下体负压室提供的准确的能力（0.1毫米汞柱内）手动或用一个计算机化信息控制从0到-100毫米汞柱的内部压力。该腔室包括一个可调节的鞍固定被检者的身体位置。透明的有机玻璃窗户让主体的腿的可视化。一个可调节的铝腰部板允许通过由主体和在髂嵴（ 图1）的水平的下体负压室佩戴的氯丁橡胶裙创建一个气密密封。 </li><li>在右侧和左侧体液锁骨关节，并在正确的地方心电图（ECG）电极，并在修改后的铅II组态左下肋（总共4个）（ 图1）对心脏速率的连续测量。 </li><li>在扶手，调整，使得手是在心脏水平支撑位置主体的怀抱。使用适当大小的手指袖口，将一个手指红外光电容积描记&#160;装置上的左和右中指的连续无创逐次心跳的测量血压。 </li><li>附加手指袖口到压力监视器。根据制造商的说明进行校准的装置和记录血压。12输入对象信息（年龄，性别，HEIGHT和重量），如果需要的话，使每搏量，心输出量和外周血管阻力由Modelflow算法计算（估计）在适当的假设。13,14 </li><li>广场上的右手食指为赔偿准备金1,12（ 图2）的连续测量手指脉搏血氧仪。 </li><li>广场上的主题鼻导管，并指示主体通过鼻子呼吸，以确保在吸气和呼气敏感的思考。鼻的空气采样将使主题为发展中国家症状的自我报告畅所欲言。鼻插管连接到二氧化碳监测仪对呼吸的连续测量和呼气末CO 2。 </li></ol> 3.执行LBNP协议<ol><li>通过点击数据采集系统的"开始"按钮，开始记录数据。 5分钟记录基线数据。启动中央hypovole的第一级MIA转动真空电机上和负压力设定到-15毫米汞柱，并保持该压力5分钟。 图3概括了协议。 </li><li>增加LBNP至-30毫米汞柱，并保持该压力5分钟。 </li><li>增加LBNP到-45毫米汞柱，并保持该压力5分钟。 </li><li>增加LBNP到-60毫米汞柱，并保持该压力5分钟。 </li><li>增加LBNP至-70毫米汞柱，并保持该压力5分钟。 </li><li>继续由-10毫米汞柱，每5分钟，以增加下体负压水平直到的协议（5分钟于-100毫米汞柱下体负压）的端部或血液动力学失代偿的点。通过按LBNP室中的压力释放按钮终止下体负压。 注:血流动力学失代偿由急剧下降，动脉收缩压低于80毫米汞柱，或主题报告晕厥前症状，如灰了（色觉丧失），隧道视野，出汗，恶心或头晕（ 图4）确定。 </li><li>下体负压停止（postLBNP恢复）后的10分钟内继续进行数据采集系统上记录数据。 </li><li>停止通过点击数据采集系统上的"停止"按钮，10分钟恢复期末记录数据。 </li><li>从分离问题的所有仪器，并从下体负压室的主题。让拍摄对象从下体负压平台下台，以确保它们没有症状离开实验室之前后坐。这项研究现已完成。 </li><li>从用于补偿储备指数（CRI），平均动脉压（MAP），心脏率和血氧饱和度值的提取采集系统下载数据文件。1,15,16 </li></ol>

<ol>
	<li>Convertino, V. A., Wirt, M. D., Glenn, J. P., Lein, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+compensatory+reserve+for+early+and+accurate+prediction+of+hemodynamic+compromise:+a+review+of+the+underlying+physiology.">The compensatory reserve for early and accurate prediction of hemodynamic compromise: a review of the underlying physiology.</a> Shock. 45 (6), 580-590 (2016).</li><li>Eastridge, B. J., 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=Death+on+the+battlefield+(2001-2011):+Implications+for+the+future+of+combat+casualty+care.">Death on the battlefield (2001-2011): Implications for the future of combat casualty care.</a> Journal of Trauma and Acute Care Surgery. 73 (6), S431-S437 (2012).</li><li>Orlinsky, M., Shoemaker, W., Reis, E. D., Kerstein, M. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+controversies+in+shock+and+resuscitation.">Current controversies in shock and resuscitation.</a> Surg. Clin. North Am. 81 (6), 1217-1262 (2001).</li><li>Wo, C. C. J., 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=Unreliability+of+blood+pressure+and+heart+rate+to+evaluate+cardiac+output+in+emergency+resuscitation+and+critical+illness.">Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness.</a> Crit Care Med. 21, 218-223 (1993).</li><li>Bruijns, S. R., Guly, H. R., Bouamra, O., Lecky, F., Lee, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+value+of+traditional+vital+signs,+shock+index,+and+age-based+markers+in+predicting+trauma+mortality.">The value of traditional vital signs, shock index, and age-based markers in predicting trauma mortality.</a> J Trauma Acute Care Surg. 74 (6), 1432-1437 (2013).</li><li>Parks, J. K., Elliott, A. C., Gentilello, L. M., Shafi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systemic+hypotension+is+a+late+marker+of+shock+after+trauma:+a+validation+study+of+Advanced+Trauma+Life+Support+principles+in+a+large+national+sample.">Systemic hypotension is a late marker of shock after trauma: a validation study of Advanced Trauma Life Support principles in a large national sample.</a> Am. J. Surg. 192 (6), 727-731 (2006).</li><li>Brunauer, A., 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+arterial+blood+pressure+associated+with+terminal+cardiovascular+collapse+in+critically+ill+patients:+a+retrospective+cohort+study.">The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients: a retrospective cohort study.</a> Crit Care. 18 (6), 719 (2014).</li><li>Hinojosa-Laborde, C., 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=Validation+of+lower+body+negative+pressure+as+an+experiomental+model+of+hemorrhage.">Validation of lower body negative pressure as an experiomental model of hemorrhage.</a> J. Appl. Physiol. 116, 406-415 (2014).</li><li>Martina, J. 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=Noninvasive+continuous+arterial+blood+pressure+monitoring+with+Nexfin(R).">Noninvasive continuous arterial blood pressure monitoring with Nexfin(R).</a> Anesthesiology. 116 (5), 1092-1103 (2012).</li><li>Imholz, B. P., Wieling, W., Langewouters, G. J., van Montfrans, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+finger+arterial+pressure:+utility+in+the+cardiovascular+laboratory.">Continuous finger arterial pressure: utility in the cardiovascular laboratory.</a> Clin. Auton. Res. 1 (1), 43-53 (1991).</li><li>Imholz, B. P. M., Wieling, W., van Montfrans, G. A., Wesseling, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fifteen+years+experience+with+finger+arterial+pressure+monitoring:+assessment+of+technology.">Fifteen years experience with finger arterial pressure monitoring: assessment of technology.</a> Cardiovasc. Res. 38, 605-616 (1998).</li><li>Roelandt, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Finger pressure reference guide. , (2005).</li><li>Harms, M. P. M., 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=Continuous+stroke+volume+monitoring+by+modelling+flow+from+non-invasive+measurement+of+arterial+pressure+in+humans+under+orthostatic+stress.">Continuous stroke volume monitoring by modelling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress.</a> Clin. Sci. 97, 291-301 (1999).</li><li>Leonetti, P., 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=Stroke+volume+monitored+by+modeling+flow+from+finger+arterial+pressure+waves+mirrors+blood+volume+withdrawn+by+phlebotomy.">Stroke volume monitored by modeling flow from finger arterial pressure waves mirrors blood volume withdrawn by phlebotomy.</a> Clin. Auton. Res. 14 (3), 176-181 (2004).</li><li>Convertino, V. A., Grudic, G., Mulligan, J., Moulton, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimation+of+individual-specific+progression+to+impending+cardiovascular+instability+using+arterial+waveforms.">Estimation of individual-specific progression to impending cardiovascular instability using arterial waveforms.</a> J. Appl. Physiol(Bethesda, Md :1985). 115 (8), 1196-1202 (2013).</li><li>Convertino, V. A., 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=Individual-specific,+beat-to-beat+trending+of+significant+human+blood+loss:+the+compensatory+reserve.">Individual-specific, beat-to-beat trending of significant human blood loss: the compensatory reserve.</a> Shock. 44 (Supplement 1), 27-32 (2015).</li><li>Cooke, W. H., Ryan, K. L., Convertino, V. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lower+body+negative+pressure+as+a+model+to+study+progression+to+acute+hemorrhagic+shock+in+humans.">Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans.</a> J. Appl. Physiol. 96, 1249-1261 (2004).</li><li>Convertino, V. A., 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=Inspiratory+resistance+maintains+arterial+pressure+during+central+hypovolemia:+implications+for+treatment+of+patients+with+severe+hemorrhage.">Inspiratory resistance maintains arterial pressure during central hypovolemia: implications for treatment of patients with severe hemorrhage.</a> Crit Care Med. 35 (4), 1145-1152 (2007).</li><li>Carter, R., Hinojosa-Laborde, C., Convertino, V. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variability+in+integration+of+mechanisms+associated+with+high+tolerance+to+progressive+reductions+in+central+blood+volume:+the+compensatory+reserve.">Variability in integration of mechanisms associated with high tolerance to progressive reductions in central blood volume: the compensatory reserve.</a> Physiol Reports. 4 (1), (2016).</li><li>Convertino, V. A., Sather, T. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Vasoactive+neuroendocrine+responses+associated+with+tolerance+to+lower+body+negative+pressure+in+humans.">Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans.</a> Clin. Physiol. 20, 177-184 (2000).</li><li>Convertino, V. A., 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=Use+of+advanced+machine-learning+techniques+for+noninvasive+monitoring+of+hemorrhage.">Use of advanced machine-learning techniques for noninvasive monitoring of hemorrhage.</a> J. Trauma. 71 (1 Suppl), S25-S32 (2011).</li><li>Convertino, V. A., Rickards, C. A., Ryan, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autonomic+mechanisms+associated+with+heart+rate+and+vasoconstrictor+reserves.">Autonomic mechanisms associated with heart rate and vasoconstrictor reserves.</a> Clin. Auton. Res. 22, 123-130 (2012).</li><li>Rickards, C. A., Ryan, K. L., Cooke, W. H., Convertino, V. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tolerance+to+central+hypovolemia:+the+influence+of+oscillations+in+arterial+pressure+and+cerebral+blood+velocity.">Tolerance to central hypovolemia: the influence of oscillations in arterial pressure and cerebral blood velocity.</a> J. Appl. Physiol. 111 (4), 1048-1058 (2011).</li><li>Johnson, B. D., 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=Reductions+in+central+venous+pressure+by+lower+body+negative+pressure+of+blood+loss+elicit+similar+hemodynamic+responses.">Reductions in central venous pressure by lower body negative pressure of blood loss elicit similar hemodynamic responses.</a> J. Appl. Physiol. 117, 131-141 (2014).</li><li>van Helmond, N., 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=Coagulation+Changes+during+Lower+Body+Negative+Pressure+and+Blood+Loss+in+Humans.">Coagulation Changes during Lower Body Negative Pressure and Blood Loss in Humans.</a> Am. J. Physiol. Heart Circ. Physiol. 309, H1591-H1597 (2015).</li><li>Gerhardt, R., Berry, J., Blackbourne, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analysis+of+life-saving+interventions+performed+by+out-of-hospital+combat+medical+personnel.">Analysis of life-saving interventions performed by out-of-hospital combat medical personnel.</a> J. Trauma. 71, S109-S113 (2011).</li><li>Pinsky, 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=Hemodynamic+evaluation+and+monitoring+in+the+ICU.">Hemodynamic evaluation and monitoring in the ICU.</a> Chest. 132 (6), 2020-2029 (2007).</li><li>Rivers, 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=Early+goal-directed+therapy+in+the+treatment+of+severe+sepsis+and+septic+shock.">Early goal-directed therapy in the treatment of severe sepsis and septic shock.</a> N.Engl.J.Med. , 1368-1377 (2001).</li><li>Rivers, E. P., 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+influence+of+early+hemodynamic+optimization+on+biomarker+patterns+of+severe+sepsis+and+septic+shock.">The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock.</a> Crit Care Med. 35 (9), 2016-2024 (2007).</li><li>Rivers, E. P., Coba, V., Whitmill, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+goal-directed+therapy+in+severe+sepsis+and+septic+shock:+a+contemporary+review+of+the+literature.">Early goal-directed therapy in severe sepsis and septic shock: a contemporary review of the literature.</a> Curr Opin Anaesthesiol. 21 (2), 128-140 (2008).</li><li>Cap, A. P., Spinella, P. C., Borgman, M. A., Blackbourne, L. H., Perkins, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Timing+and+location+of+blood+product+transfusion+and+outcomes+in+massively+transfused+combat+casualties.">Timing and location of blood product transfusion and outcomes in massively transfused combat casualties.</a> J. Trauma. 73, S89-S94 (2012).</li><li>Spinella, P. C., Perkins, J. G., Grathwohl, K., Beekley, A., 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=Warm+fresh+whole+blood+is+independently+associated+iwth+improved+survival+for+patients+with+combat-related+traumatic+injuries.">Warm fresh whole blood is independently associated iwth improved survival for patients with combat-related traumatic injuries.</a> J. Trauma. 66, S69-S76 (2009).</li><li>Kragh, J., 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=Survival+with+emergency+tourniquet+use+to+stop+bleeding+in+major+limb+trauma.">Survival with emergency tourniquet use to stop bleeding in major limb trauma.</a> Ann Surgery. 249 (1), 1-7 (2009).</li><li>Chung, K. K., 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=Continous+renal+replacement+therapy+improves+survival+in+severly+burned+military+casualties+with+acute+kidney+injury.">Continous renal replacement therapy improves survival in severly burned military casualties with acute kidney injury.</a> J. Trauma. 64, S179-S187 (2008).</li><li>Stewart, C. L., 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+compensatory+reserve+for+early+and+accurate+prediction+of+hemodynamic+compromise:+case+studies+for+clinical+utility+in+acute+care+and+physical+performance.">The compensatory reserve for early and accurate prediction of hemodynamic compromise: case studies for clinical utility in acute care and physical performance.</a> J Special Op. Med. 16, 6-13 (2016).</li></ol>

The authors declare that they have no competing financial interests. The views expressed herein are the private views of the authors and are not to be construed as representing those of the US Department of the Army or the US Department of Defense.

用下体负压引起中央血容量进步和不断的减少，我们能够诱导血液动力学失代偿的主题典型的响应，其特点是低血压和心动过缓（ 图7）突然发作。理解到出血集成代偿反应是非常复杂的是很重要的，19从而在公差失血显著个体变异。1同样地，一些个体具有相对响应的补偿机制，而其他不那样有效地补偿。因此，在该协议中的关键步骤是在实验进行到心血管失代偿的?...

心血管系统的最重要的功能是足够的灌注（血流量和氧输送）到身体的所有组织中，通过动脉血压稳态调节控制。补偿各种机制（ 例如 ，自主神经系统的活动，心率和收缩，静脉回流，血管收缩，呼吸）有助于维持在组织氧气的正常生理水平1的减少在循环血液量例如那些引起出血可以妥协心血管补偿机制的能力，并最终导致低动脉血压，认真组织缺氧，循环性休克，可以是致命的。 严重出血（ 即出血性休克）引起的循环性休克是死亡的主要原因是由于创伤。2一个防止病人从最具挑战性的方面发展的冲击是我们的没有认识到它的早期发病。朝向休克的发展进展的早期和准确的评估目前在临床上由提供在失血因为人体的众多代偿的早期阶段变化很小的生命体征测量技术（ 即，医疗监视器）限定对调节血压的机制。3-6因此，衡量的总和身体的储备，以弥补血液流失的能力代表组织灌注状态的最准确的反映和发展电击的危险。1该储备金被称为。它可以通过改变实时测量动脉波形的特点准确地评估代偿储备代偿储备的枯竭1复制的危重患者低血压突然发作观察到的终端心血管功能不稳定;被称为血液动力学装饰的条件mpensation 7 在人类持续失血期间代偿储备和调节血压的利用之间的关系可以用一套完整的生理测量的实验室证明（ 如血压，心脏率，动脉血氧饱和度，每搏输出量，心输出量，血管阻力，呼吸，脉搏的性格，精神状态，呼气末二氧化碳 ，组织氧）期间，中央血容量相似出血期间发生持续逐步削减通过标准生理监测提供。降低的中心血量可以无创性与下体负压逐步增加（LBNP）诱发。8使用生理测量和下体负压，如何评价人体的补偿减少中央血量可以很容易地能力概念理解的这种组合恶魔trated。该研究描述了实验预习制备，模拟出血期间相对于其他生理反应代偿性反应的示范，和结果的postlab评价。用于做出补偿准备金的测量实验技术证实在人类志愿者。

<table><tbody><tr><td>Dynamic Research Evaluation Workstation (DREW) data acquisition syetem</td><td>NA</td><td>NA</td><td>Custom Built by ISR personnel. The DREW allows for time synchronization of both digital and analog signal data collection from up to 16 independent instruments with a sampling rate of 1,000 Hz.</td></tr><tr><td>Finometer</td><td>Finapress Medical Systems (FMS)</td><td>Model 1</td><td>Device that provides noninvasive, continuous measurements of brachial artery blood pressure and arterial oxygen saturation (SpO&lt;sub&gt;2&lt;/sub&gt;) using two separate infrared finger photophlethymography cuff sensors.</td></tr><tr><td>BCI Capnocheck Plus</td><td>Smith Medical PM Inc.</td><td>9004</td><td>Capnograph used to measure end tidal CO&lt;sub&gt;2&lt;/sub&gt; and respiration rate</td></tr><tr><td>CipherOX&amp;nbsp;</td><td>Flashback Technologies Inc.</td><td>R200</td><td>Investigational device used to calculate Compensatory Reserve Index (CRI)</td></tr><tr><td>Nonin 9560 Pulse Oximeter</td><td>Nonin</td><td>9560</td><td>finger pulse oximeter</td></tr><tr><td>Lower Body Negative Pressure Chamber (LBNP)</td><td>NASA</td><td>79K32632-1</td><td>Custom Chamber built by NASA</td></tr><tr><td>ECG Biotach</td><td>Gould</td><td>13-6615-65</td><td>Electrocardiograph for measuring ECG</td></tr><tr><td>Nasal CO&lt;sub&gt;2&lt;/sub&gt; Sample Line</td><td>Salter Labs</td><td>REF 4000</td><td>Latex free nasal cannula for sampling expired air</td></tr></tbody></table>

integrated compensatory responses in a human model of hemorrhage

出血是创伤有关的死亡的首要原因，部分是由于失血的严重性的早期诊断是困难的。出血的患者的评估是困难的，因为目前的临床工具提供的生命体征，由于代偿机制仍然期间出血的早期阶段稳定的措施。因此，有必要了解和测量的该补偿减少循环血液量，以及他们如何持续渐进出血时改变机构的总积分。人体的储备，以弥补减少循环血容量被称为"补偿性储备"。代偿储备可以在动脉波形与使用一个高功率的计算机的测量的特征的变化的实时测量来精确地进行评价。下体负压（LBNP）已经显示出模拟许多生理反应的与出血相关的人类，并且是用来研究对出血的代偿性反应。这项研究的目的是演示过程中中央血量逐步削减与下体负压为出血的模拟储备代偿如何评估。

该下体负压过程会导致在周围的下部躯干和腿的空气压力降低。作为这种真空逐渐增加，从头部和上部躯干在下体血容量移位来创建中央血容量不足的状态。在中央血容量逐步减少（ 即 ，LBNP）产生与红外线手指光体积描记（ 图5）测量的动脉波形的特征显著改变。该补偿储备指数（CRI）是从采用了独特的机器学习算法，其分析在波形特性的变化来计算...

Watch this Scientific Journal Video about Integrated Compensatory Responses in a Human Model of Hemorrhage at JoVE.com

Integrated Compensatory Responses in a Human Model of Hemorrhage

该协议的目的是证明的技术用于使用下体负压作为可用于定量的人类代偿机制血容量赤字总积分的人类出血的非侵入性的实验模型测量减少中央血容量代偿反应。

在出血的人体模型集成的代偿反应

Hemorrhage is the leading cause of trauma-related deaths, partly because early diagnosis of the severity of blood loss is difficult. Assessment of ...

integrated-compensatory-responses-in-a-human-model-of-hemorrhage

Research

JoVE Journal

Medicine

12.4K 次观看.  JBSA Fort Sam Houston. 该协议的目的是证明的技术用于使用下体负压作为可用于定量的人类代偿机制血容量赤字总积分的人类出血的非侵入性的实验模型测量减少中央血容量代偿反应。 

视频: Integrated Compensatory Responses in a Human Model of Hemorrhage

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

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, 2, 3, 4, 5 These signaling events can also lead to sepsis and/or multiple organ dysfunction (MOD). 6, 7, 8, 9 It is critical then to investigate the causes of suppressed immune function and detrimental signaling cascades in order to develop more effective ways to help patients who suffer from traumatic injuries. 10 This fixed pressure Hemorrhagic Shock (HS) procedure, although technically challenging, is an excellent resource for investigation of these pathophysiologic conditions. 11, 12, 13 Advances in the assessment of biological systems, i.e. Systems Biology have enabled the scientific community to further understand complex physiologic networks and cellular communication patterns. 14 Hemorrhagic Shock has proven to be a vital tool for unveiling these cellular communication patterns as they relate to immune function. 15, 16, 17, 18 This procedure can be mastered! This procedure can also be used as either a fixed volume or fixed pressure approach. We adapted this technique in the murine model to enhance research in innate and adaptive immune function. 19, 20, 21 Due to their small size HS in mice presents unique challenges. However due to the many available mouse strains, this species represents an unparalleled resource for the study of the biologic responses. The HS model is an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, i.e. DAMP and PAMP upregulation as it elicits distinct responses that differ from other forms of shock. 22, 23, 24, 25 The development of transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up and down regulation of signal transduction after severe blood loss, i.e. HS and trauma 26, 27, 28, 29, 30. 
There are numerous resuscitation methods (R) in association with HS and trauma. 31, 32, 33, 34 A fixed volume resuscitation method of solely lactated ringer solution (LR), equal to three times the shed blood volume, is used in this model to study endogenous mechanisms such as remote organ injury and systemic inflammation. 35, 36, 38 This method of resuscitation is proven to be effective in evaluating the effects of HS and trauma 38, 39.

The Hemorrhagic Shock model has been a reliable and reproducible resource facilitating the identification and understanding of signaling cascades associated with inflammation and end-organ damage after trauma. This article provides a step-by-step description of surgical and mechanical aspects associated with the Hemorrhagic Shock experimental procedure in mice.

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

Modeling Intracerebral Hemorrhage in Mice: Injection of Autologous Blood or Bacterial Collagenase 

Spontaneous intracerebral hemorrhage (ICH) defines a potentially life-threatening neurological malady that accounts for 10-15% of all stroke-related hospitalizations and for which no effective treatments are available to date1,2. Because of the heterogeneity of ICH in humans, various preclinical models are needed to thoroughly explore prospective therapeutic strategies3. Experimental ICH is commonly induced in rodents by intraparenchymal injection of either autologous blood or bacterial collagenase4. The appropriate model is selected based on the pathophysiology of hemorrhage induction and injury progression. The blood injection model mimics a rapidly progressing hemorrhage. Alternatively, bacterial collagenase enzymatically disrupts the basal lamina of brain capillaries, causing an active bleed that generally evolves over several hours5. Resultant perihematomal edema and neurofunctional deficits can be quantified from both models. In this study, we described and evaluated a modified double injection model of autologous whole blood6 as well as an ICH injection model of bacterial collagenase7, both of which target the basal ganglia (corpus striatum) of male CD-1 mice. We assessed neurofunctional deficits and brain edema at 24 and 72 hr after ICH induction. Intrastriatal injection of autologous blood (30 &mu;l) or bacterial collagenase (0.075U) caused reproducible neurofunctional deficits in mice and significantly increased brain edema at 24 and 72 hr after surgery (p&lt;0.05). In conclusion, both models yield consistent hemorrhagic infarcts and represent basic methods for preclinical ICH research.

Modeling Intracerebral Hemorrhage in Mice: Injection of Autologous Blood or Bacterial Collagenase

Clinically relevant animal models of intracerebral hemorrhage (ICH) are needed to extend our knowledge of hemorrhagic stroke and to examine novel therapeutic strategies. In this study, we describe and evaluate two ICH models that implement unilateral injections of either autologous whole blood or bacterial collagenase into the basal ganglia (corpus striatum) of mice.

在小鼠的脑出血模型：注射自体血液或细菌胶原酶

Spontaneous intracerebral hemorrhage (ICH) defines a potentially life-threatening neurological malady that accounts for 10-15% of all stroke-related ...

A Murine Model of Subarachnoid Hemorrhage

In this video publication a standardized mouse model of subarachnoid hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of Willis perforation (CWp) and proven by intracranial pressure (ICP) monitoring. Thereby a homogenous blood distribution in subarachnoid spaces surrounding the arterial circulation and cerebellar fissures is achieved. Animal physiology is maintained by intubation, mechanical ventilation, and continuous on-line monitoring of various physiological and cardiovascular parameters: body temperature, systemic blood pressure, heart rate, and hemoglobin saturation. Thereby the cerebral perfusion pressure can be tightly monitored resulting in a less variable volume of extravasated blood. This allows a better standardization of endovascular filament perforation in mice and makes the whole model highly reproducible. Thus it is readily available for pharmacological and pathophysiological studies in wild type and genetically altered mice.

A standardized mouse model of subarachnoid hemorrhage by intraluminal Circle of Willis perforation is described. Vessel perforation and subarachnoid bleeding are monitored by intracranial pressure monitoring. In addition various vital parameters are recorded and controlled to maintain physiologic conditions.

蛛网膜下腔出血的小鼠模型

In this video publication a standardized mouse model of subarachnoid  hemorrhage (SAH) is presented. Bleeding is induced by endovascular Circle of  Willis ...

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

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.

Uncontrolled hemorrhage, an important cause of mortality among trauma patients, can be modeled using a standard liver laceration in a murine model. This model results in consistent blood loss, survival, and allows for testing hemostatic agents. This article provides the step-by-step process to perform this valuable model.

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 ...

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

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the forefront of trauma care in recent years. Since complete aortic occlusion presents serious concerns, the concept of partial aortic occlusion has gained a growing attention. Here, we present a large animal model of hemorrhagic shock to investigate the effects of a novel partial aortic balloon occlusion catheter and compare it with a catheter that works on the principles of complete aortic occlusion. Swine are anesthetized and instrumented in order to conduct controlled fixed-volume hemorrhage, and hemodynamic and physiological parameters are monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted and inflated in the supraceliac aorta for 60 min, during which the animals receive whole-blood resuscitation as 20% of the total blood volume (TBV). Following balloon deflation, the animals are monitored in a critical care setting for 4 h, during which they receive fluid resuscitation and vasopressors as needed. The partial aortic balloon occlusion demonstrated improved distal mean arterial pressures (MAPs) during the balloon inflation, decreased markers of ischemia, and decreased fluid resuscitation and vasopressor use. As swine physiology and homeostatic responses following hemorrhage have been well-documented and are like those in humans, a swine hemorrhagic shock model can be used to test various treatment strategies. In addition to treating hemorrhage, aortic balloon occlusion catheters have become popular for their role in cardiac arrest, cardiac and vascular surgery, and other high-risk elective surgical procedures.

Here, we present a protocol demonstrating a hemorrhagic shock model in swine that uses aortic occlusion as a bridge to definitive care in trauma. This model has application in testing a wide range of surgical and pharmacological therapeutic strategies.

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 ...

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

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an insufficient oxygen supply and irreversible organ failure. The brain exerts only limited compensation capacities and is particularly at high risk of severe hypoxic damage.This article demonstrates the reproducible induction of life-threatening hemorrhagic shock in a porcine model by means of calculated blood withdrawal. We titrate shock induction guided by near-infrared spectroscopy&#160;and extended hemodynamic monitoring to display systemic circulatory failure, as well as cerebral microcirculatory oxygen depletion. In comparison to similar models that primarily focus on predefined removal volumes for shock induction, this approach highlights a titration by means of the resulting failure of macro- and microcirculation.

Hemorrhagic shock is a severe complication in seriously injured patients, which leads to life-threatening oxygen undersupply. We present a standardized method to induce hemorrhagic shock via blood withdrawal in pigs that is guided by hemodynamics and microcirculatory cerebral oxygenation.

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 ...

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional deficits. Numerous studies by our group and others have shown that mTBI stimulates cytokine expression and activates microglia, decreases cerebral blood flow and metabolism, and impairs cerebrovascular reactivity. Moreover, several works have reported an association between derangements in these neuroinflammatory and hemodynamic markers and cognitive impairments. Herein we detail methods to characterize the neuroinflammatory and hemodynamic tissue response to mTBI in mice. Specifically, we describe how to perform a weight-drop model of mTBI, how to longitudinally measure cerebral blood flow using a non-invasive optical technique called diffuse correlation spectroscopy, and how to perform a Luminex multiplexed immunoassay on brain tissue samples to quantify cytokines and immunomodulatory phospho-proteins (e.g., within the MAPK and NF&#954;B pathways) that respond to and regulate activity of microglia and other neural immune cells. Finally, we detail how to integrate these data using a multivariate systems analysis approach to understand the relationships between all of these variables. Understanding the relationships between these physiologic and molecular variables will ultimately enable us to identify mechanisms responsible for mTBI.

This protocol presents methods to characterize the neuroinflammatory and hemodynamic response to mild traumatic brain injury and to integrate these data as part of a multivariate systems analysis using partial least squares regression.

创伤性脑损伤的神经炎症和血流动力学反应的系统分析

Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional ...

神经科学

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.

<meta charset="utf8"></head><body>创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

Intraparenchymal hemorrhage and neuroinflammation accompanied by cerebral contusion can trigger severe secondary brain injury. This protocol details a mouse controlled cortical impact (CCI) model allowing researchers to study hemorrhage contusion and post-traumatic immune responses and explore potential therapeutics.

创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the ...

Description of a Swine Infant Model of Volume-Controlled Hemorrhagic Shock

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to guide resuscitation and comparison between different therapies is difficult in children due to the inherent heterogeneity of this population. As a result, compared to adults, appropriate management of pediatric hemorrhagic shock is still not well established. In addition, the scarcity of pediatric patients with hemorrhagic shock precludes the development of clinically relevant studies. For this reason, an experimental pediatric animal model is necessary to study the effects of hemorrhage in children as well as their response to different therapies. We present an infant animal model of volume-controlled hemorrhagic shock in anesthetized young pigs. Hemorrhage is induced by withdrawing a previously calculated blood volume, and the pig is subsequently monitored and resuscitated with different therapies. Here, we describe a precise and highly reproducible model of hemorrhagic shock in immature swine. The model yields hemodynamic data that characterizes compensatory mechanisms that are activated in response to severe hemorrhage.

This article aims to provide researchers with a detailed and accessible guide to set up an infant porcine model of hemorrhagic shock.

容量控制性失血性休克的猪婴儿模型的描述

Hemorrhagic shock is a leading cause of morbidity and mortality in pediatric patients. Interpretation of the clinical indicators validated in adults to ...

在出血的人体模型集成的代偿反应

摘要

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此视频中的章节

固定体积或固定压力：失血性休克的小鼠模型

在小鼠的脑出血模型：注射自体血液或细菌胶原酶

蛛网膜下腔出血的小鼠模型

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

完全性和部分主动脉闭塞治疗猪失血性休克

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

创伤性脑损伤的神经炎症和血流动力学反应的系统分析

创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

创伤性出血挫伤和神经炎症的临床前受控皮质影响模型

容量控制性失血性休克的猪婴儿模型的描述