资金来源/编号分子生物学失血性休克GM053789

1。仪器及手术现场准备: 1。仪器准备。 所有外科手术使用的无菌技术进行。一个蓝色的手术垫和无菌战地包扎。所有的材料和工具消毒后方可使用。 6-0缝线，棉花尖端涂药，纱布，雄性3路活塞，和仪器，高压灭菌消毒。传感器，PE 50，PE - 10管，环氧乙烷灭菌。收到所有3路旋塞，注射器和针头是无菌的。 6-0缝合切成1英寸件（6件/动物），并投入小消毒袋。棉头喷头，4x4的纱布广场，雄性3路活塞投入无论是小型或中型的消毒袋和灭菌。我们的手术器械，高压灭菌消毒每天晚上。他们手术后，使用抗菌肥皂和自来水冲洗。他们被允许在一个干净的手术蓝色垫干。他们然后小心地放入灭菌袋和消毒，使用第二天。 由于传感器和油管，塑料部件，它们必须使用，即环氧乙烷气体消毒。 PE - 10管切成5寸片，摆成一个小的消毒袋。 PE - 50管被切割成18英寸的作品，并放置到中等杀菌袋。 2。手术野。 第一，要设置的手术视野，打开热珠消毒器，以确保它达到适当的温度300-350 ° F，开始手术前。然后接下来的步骤进行手术蓝色垫放在酒精抹台式。一垫，在显微镜下，其他循环加热垫的BP分析仪是位于。将无菌敷料领域的两个手术蓝色垫。填充不锈钢仪器托盘的1 / 3，用70％酒精的方式。足够使用70％乙醇，以涵盖所​​有的手术器械。使用一个单独的无菌战地包扎，并将其放置在显微镜下一个。将所有消毒，缝合线，纱布，在这个无菌领域和导管。开放消毒和缝合，不污染触摸时要小心。最好是这样做安装程序时，使用无菌手套。 2。机械设置和程序: 1。导管设置。 要设置右腿小鼠导管，用来测量BP，第一，穿上无菌手套。然后得到无菌的PE - 10油管从高压灭菌袋。抓住中间用食指和拇指留下约一英寸它们之间的油管。拉伸这只是一个位，使其直径细导管插入帮助部分油管。拉伸后的油管削减一半使用无菌剪刀。 5英寸的管材，现在应该是两件半英寸，长度约2。确保锥拉伸结束。 *请勿角度斜边太多，因为这可能会增加退出管腔的机会，通过血管壁的下部戳。 插入一个30G针头钝油管未拉伸。获取的无菌1CC注射器和一个3路阀。使用酒精擦拭消毒10CC无菌小瓶含有肝素生理盐水溶液（0.1毫升Heparin/9.9ml生理盐水）的顶部。肝素溶液0.6 - 0.7cc填充注射器。将3路，对面直接就是从男性端30G的针头和导管。填补了活塞，30G针，与肝素液管和PE - 10。确保得到系统中所有的气泡。除去所有的气泡，最有效的方法是利用重力。同时让管吊着的台式针指向地面。给手指轻弹针枢纽和气泡会浮到肝素溶液的顶部。从3路删除30G针头和消除气泡。提取液在3路到1CC注射器回，以消除任何气泡，被困在3路，3路，并重新油管。大约1CC的混合物，应留在注射器中。鼠标将收到约0.05cc 1U肝素/鼠标这种混合物约等于（冲洗导管插入时保持通畅）。完成的导管放置到与手术器械的无菌敷料领域。 要设置左腿小鼠导管遵循相同的程序与上述3路阀异常。左腿是用来绘制的血液和3路阀是不需要的。填写1CC另一个无菌注射器用肝素盐水混合物0.15 - 0.2cc。挂钩的30G针头和PE - 10 tubi吴直接1CC注射器。填写左腿导管系统与解决方案。过多的气泡，从这个系统中删除。完成导管放置到与消毒无菌敷料领域。 2。传感器设置。 挂钩无菌传感器根据微地中海规范的Digi - MED双酚A 400分析仪。将3路阀的换能器两端。乳酸林格氏液（LR）填写一个10CC的注射器，将它附加到3路，使换能器将趴在台式平。一个23G的针头插入的预切一块18英寸presterilized PE - 50管两端。 10CC的注射器连接的PE - 50管的一端连接到3路。填写三路与LR和PE - 50设置。确保所有气泡在上一节所描述的系统。重新装上传感器和3路，填补传感器和第二 LR 3。最后，将金属雄性leur锁活塞附件右腿小鼠导管管材PE - 50 23G针。 *流体传感器仍然在运转时，它是至关重要的。 *校准和零程序，根据微MED协议。 3。手术和实验程序: 1。外科手术。 首先管理Pentobarbitol钠腹腔注射（Nembutol）（70mg/kg @ 1:10稀释）。完成此过程，首先，从它的笼子里使用它的尾巴的基地（最近端）采摘鼠标。接下来，放在笼子顶部的动物，同时仍持有它的尾巴。鼠标，仅仅落后的前爪两侧用大拇指和中指抓住鼠标的颈背。食指是用来拉头/颈部皮肤对颈背固定头部。鼠标的尾部，然后包裹，和小指和无名指之间举行无名指同时按下鼠标的脊椎腰椎地区。鼠标应在5分钟之内睡着了。后动物麻醉到手术的金属板到位，在仰卧位。宽松循环磁带技术是用来固定用胶带其四肢的动物。宽松的循环技术需要简单地切细条状的磁带和松散的环绕着每个脱颖而出四肢伪劣的爪子，和周围的劣势后肢足跖每个磁带。磁带，然后停留本身超过磁带的左侧连接到电路板。这使得小鼠的四肢，以承担更自然的解剖位置。动物的腹部和腹股沟区，然后使用奥斯特A5的快船大小40刀片剃。一个4x4纱布浇上用优碘，然后消灭无菌手术区。 固定和灭菌后，与异氟醚1CC的鼻锥放置了几秒钟，然后才作出最初的切口对老鼠的鼻子。鼻锥由一个50CC的锥形管，用纱布填充。切出的试管底部的一半是创建一个鼠标的鼻子内休息无接触的空间。 50CC锥形年底被放在一个上限（组织储存容器的底部），以确保异氟醚蒸气，不逃避。一旦动物的呼吸开始放慢，是一个4 - 5mm的小切口，在皮肤平行内部的左腹部和左横abdominus肌斜肌。股静脉和动脉夹层如下。确保不破坏周围的肌肉或触摸神经。要开始剥离，单独从斜肌和腹横肌，抓住与腹部连接dumonts的脂肪组织的脂肪组织。这个组织拉离肌壁。然后，生硬的解剖一起戏弄了筋膜和脂肪组织中，使用其他dumonts对腹肌​​。仅仅在于脂肪组织下这股静脉，股神经和动脉。 *请务必不要损坏股intermedius，内侧和外侧肌肉，股四头肌或股直肌。实在是没有必要抢，甚至触摸这些肌肉。 *不要触摸股神经敛在于它旁边的脂肪组织，神经解剖走。这个组织的横向拉的静脉和动脉和神经，因为它是在这个组织中。由于神经横向拉，钝性解剖筋膜，点向下放置其他dumonts，对动脉开放和关闭它们。船只是非常肤浅的，所以一定不要深入底层的肌肉。神经分离后，使用的dumonts分离筋膜肌肉血管。保持dumonts封闭滑dumonts背船只。 dumonts的尖端出现在另一侧的静脉，打开他们生硬的解剖筋膜。保持dumonts背的船只，并抢了先缝合。放入dumonts缝合和拉之间的血管和肌肉底层的开放缝合。同样，也没有必要以损害任何周围的肌肉。 共3，6-0缝线周围放置的静脉和动脉。缝合1是最近端腹肌。打结，但离开它松散和止血。凹边缘的止血钳，应由动物的腹腔。缝合2位置最远端。这种缝合线可连接立即结扎血管和hemostated，凹侧再次下跌。远端和近端的缝合线是用来拉绷紧的船只（防止失血），并解除他们有点帮助导管插入。缝合3是一个导管支持缝合。把这个之间的远端和近端缝合的缝合。把一个松散的结，将导管插入血管内后用于保护。后缝合是安全的，确定由厚血管壁的动脉。这是很白。制作一个小切口动脉顶端用microscissors。请远端缝合关闭这个洞，所以有充裕的金额最初的导管插入动脉。使用dumonts打开放到动脉血管管腔的dumonts的一端，并关闭在血管壁孔。可以肯定的中间缝合，因此它可以用来装到位后首次插入导管的近端动脉孔。按住动脉管壁，管腔推入导管，在导管的拉动船只。轻轻地配合了中间支撑的缝合固定到位导管。释放近端止血。这个版本将放松近端缝合，重新缝合血管周围。此时，动脉血压应推回血进入导管。应在导管中可见的血液脉动。杜蒙一个导管周围的血管和使用其他导管推入约4 - 5mm的船只。控股导管周围的血管，有助于防止动脉撕裂。导管尖端下方内部的倾斜和横向abdominus肌肉休息。预防血液凝块在动脉线，撤出导管进入血液，并把它放回鼠标多次注入肝素液。为双侧股动脉插管的另一条腿重复此过程。钩动物的生理参数监护仪，即双酚A - 400分析仪和冲洗动脉行。手术开放，保持周围组织湿润放入无菌生理盐水1或2滴。一定要保持这方面的整个过程中饱和。将动物的整个过程，以帮助保持无菌敷料，无菌领域。 手术器械放入70％酒精，并用无菌纱布。放入热珠〜20秒的灭菌消毒与动物之间。取出手术器械，并用70％酒精喷洒，以帮助他们冷静下来。放置到无菌垫。确保有左无酒精的文书，将滴灌进入下一个动物。 2。失血性休克。 超过15分钟。时间表，约1 / 2鼠标的血容量被撤回，实现了平均2832毫米汞动脉压。 *对于2527克鼠标的初始音量，以达到所需的压力撤回血液约0.6cc 此过程是一个固定的压力的方法，而不是一个固定的量。这些程序可以，但是应遵循固定的压力和固定量的出血。虽然始终被​​监控，动物将保持在1.5 -3小时失血性休克。由于动物试图弥补和平均动脉压开始略有回升（通过BP /人力资源分析仪可见）撤出更多的血液，以达到所需的压力。虽然很少在房协的过程中需要补充（0.05cc Nembutol IP），动物的呼吸，运动晶须，反射测试，和数字的BP / HR阅读，将有助于确定何时需要动物麻醉的补充。动物保持灯泡和循环加热垫，以帮助保持温度36-37 ° C到失血性休克过程。温度是通过直肠探头检查。 3。复苏。 后震荡时间elapsES，动物复活（R）的使用乳酸林格（LR）在一个固定体积的3倍每个动物的流血量的解决方案。土地注册处卷管理，通过设置，免除注射泵，以恒定速率，超过15分钟的量。间隔。取下导管结扎3缝线使用的船只。刚刚过去的近端缝合拉导管和配合这个缝合完全关闭。这将防止任何失血。侧支循环，防止缺血后肢。 4。邮政Rescitation。 后ř两个后肢开口缝起来使用无菌4-0 PDSII缝合。宽松循环磁带被删除，动物被放置到一个干净的笼子里，这是保存在几个小时后恢复循环加热垫。动物开始从麻醉中唤醒，妥善管理疼痛，镇痛，必须管理。丁丙诺啡（为0.1mg/kg）皮下注射动物开始的体力活动，但不前，所以不会危及呼吸功能。使用积极的手术后监测IACUC批准的协议，动物个体的行为，和目前的医疗条件保证的建议。 4。成功的秘密: <ol><li>当解剖的船只，可千万不要触摸股神经</li><li>注意不要损伤股直肌，腹直肌外侧，股内侧肌肉。实在是没有必要抢，甚至触摸这些肌肉。 </li><li>不要使导管太锋利，因为这锥角会导致退出管腔导管和不受控制的出血</li><li>请一定要采取额外的努力，保持尽可能无菌。 </li><li>确保有任何导管或传感器系统无气泡。 </li><li>确保有LR在传感器的液体，而它在操作。试运行可能会损害您的BP系统。 </li><li>使小动脉孔。 </li><li>使动脉孔关闭远端缝合。 </li><li>推同时拉动船只超过它，以避免翻录动脉导管插入导管。 </li><li>一定要保持在饱和用无菌生理盐水，以防止不受控制的组织损伤或液体流失腿手术开口。 </li><li>耐心和技巧是至关重要的。 </li><li>整个实验过程中密切注意动物的生理。 </li></ol> 5。发布执行的担忧: <ol><li>检查中腿部缺血。虽然抵押品的流动应防止这种情况。 </li><li>动物可能有麻烦，手术操作及相关炎症的结果作为使用后肢。管理适当的疼痛。 </li><li>触摸和随后破坏的神经可能会导致动物无法调动。 </li></ol>

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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toll-like+receptor-4+signaling+mediates+hepatic+injury+and+systemic+inflammation+in+hemorrhagic+shock.">Toll-like receptor-4 signaling mediates hepatic injury and systemic inflammation in hemorrhagic shock.</a> J Am Coll Surg. 202, 407-417 (2006).</li><li>Meng, Z. H., Dyer, K., Billiar, T. R., Tweardy, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Essential+role+for+IL-6+in+postresuscitation+inflammation+in+hemorrhagic+shock.">Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock.</a> Am J Physiol Cell Physiol. 280, C343-C351 (2001).</li><li>McCloskey, C. A., Kameneva, M. V., Uryash, A., Gallo, D. J., Billiar, T. 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H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prolonged+immunodepression+after+trauma+and+hemorrhagic+shock.">Prolonged immunodepression after trauma and hemorrhagic shock.</a> J Trauma. 44, 335-341 (1998).</li><li>Abraham, E., Chang, Y. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Haemorrhage-induced+alterations+in+function+and+cytokine+production+of+T+cells+and+T+cell+subpopulations.">Haemorrhage-induced alterations in function and cytokine production of T cells and T cell subpopulations.</a> Clin. Exp. Immunol. 90, 497-502 (1992).</li><li>Peitzman, A. B., Billiar, T. R., Harbrecht, B. G., Kelly, E., Udekwu, A. O., Simmons, R. 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P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+silico+and+in+vivo+approach+to+elucidate+the+inflammatory+complexity+of+CD14-deficient+mice.">In silico and in vivo approach to elucidate the inflammatory complexity of CD14-deficient mice.</a> Mol Med. 12, 88-96 (2006).</li><li>Kobbe, P., Stoffels, B., Schmidt, J., Tsukamoto, T., Gutkin, D. W., Bauer, A. J., 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=IL-10+deficiency+augments+acute+lung+but+not+liver+injury+in+hemorrhagic+shock.">IL-10 deficiency augments acute lung but not liver injury in hemorrhagic shock.</a> Cytokine. 45, 26-31 (2009).</li><li>Prince, J. M., Ming, M. J., Levy, R. M., Liu, S., Pinsky, D. J., Vodovotz, Y., 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=Early+Growth+Response+1+mediates+the+systemic+and+hepatic+inflammatory+response+initiated+by+hemorrhagic+shock.">Early Growth Response 1 mediates the systemic and hepatic inflammatory response initiated by hemorrhagic shock.</a> Shock. 27, 157-164 (2007).</li><li>Matsutani, T., Samy, A. n. a. n. t. h. a., Kang, T. S., Bland, S. -. C., Chaudry, K. I., H, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+genetic+background+influences+severity+of+immune+responses+following+trauma-hemorrhage.">Mouse genetic background influences severity of immune responses following trauma-hemorrhage.</a> Cytokine. 30, 168-176 (2005).</li><li>Rushing, G. D., Britt, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reperfusion+injury+after+hemorrhage:+a+collective+review.">Reperfusion injury after hemorrhage: a collective review.</a> Ann Surg. 247, 929-937 (2008).</li><li>Makley, A. T., Goodman, M. D., Friend, L. W., Bailey, S. R., Lentsch, A. B., Pritts, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Damage+control+resuscitation+with+fresh+blood+products+attenuates+the+systemic+inflammatory+response+following+hemorrhagic+shock.">Damage control resuscitation with fresh blood products attenuates the systemic inflammatory response following hemorrhagic shock.</a> J Surg Res. 158, 423-423 (2010).</li><li>Stansbury, L. G., Dutton, R. P., Stein, D. M., Bochicchio, G. V., Scalea, T. M., Hess, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controversy+in+trauma+resuscitation:+do+ratios+of+plasma+to+red+blood+cells+matter?.">Controversy in trauma resuscitation: do ratios of plasma to red blood cells matter?.</a> Transfus Med Rev. 23, 255-265 (2009).</li><li>Gao, J., Zhao, W. X., Xue, F. S., Zhou, L. J., Yu, Y. H., Zhou, H. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+different+resuscitation+fluids+on+acute+lung+injury+in+a+rat+model+of+uncontrolled+hemorrhagic+shock+and+infection.">Effects of different resuscitation fluids on acute lung injury in a rat model of uncontrolled hemorrhagic shock and infection.</a> J Trauma. 6, 1213-1219 (2009).</li><li>Maier, S., Holz-Holzl, C., Pajk, W., Ulmer, H., Hengl, C., Dunser, M., Haas, T., Velik-Salchner, C., Fries, D., Greiner, A., Hasibeder, W., Knotzer, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microcirculatory+parameters+after+isotonic+and+hypertonic+colloidal+fluid+resuscitation+in+acute+hemorrhagic+shock.">Microcirculatory parameters after isotonic and hypertonic colloidal fluid resuscitation in acute hemorrhagic shock.</a> J Trauma. 66, 33-45 (2009).</li><li>Stahel, P. F., Smith, W. R., Moore, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+trends+in+resuscitation+strategy+for+the+multiply+injured+patient.">Current trends in resuscitation strategy for the multiply injured patient.</a> Injury. 40, 27-35 (2009).</li><li>Dar, D. E., Soustiel, J. F., Zaaroor, M., Em, B., L, A., Shapira, Y., Semenikhina, L., Solopov, A., Krausz, M. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Moderate+lactated+ringer's+resuscitation+yields+best+neurological+outcome+in+controlled+hemorrhagic+shock+combined+with+brain+injury+in+rats.">Moderate lactated ringer's resuscitation yields best neurological outcome in controlled hemorrhagic shock combined with brain injury in rats.</a> Shock. , (2009).</li><li>Moon, P. F., Hollyfield-Gilbert, M. A., Myers, T. L., Uchida, T., Kramer, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluid+compartment+in+hemorrhaged+rats+after+hyperosmotic+crystalloid+and+hyperoncotic+crystalloid+resuscitation.">Fluid compartment in hemorrhaged rats after hyperosmotic crystalloid and hyperoncotic crystalloid resuscitation.</a> Am J Physiol. 270, F1-F8 (1996).</li><li>Perel, P., Roberts, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Colloids+vs+crystalloids+for+fluid+resuscitation+in+critically+ill+patients.">Colloids vs crystalloids for fluid resuscitation in critically ill patients.</a> Cochrane Database System Rev. 4, CD000567-CD000567 (2007).</li></ol>

监督，并按照机构的动物护理和使用委员会规定的准则和法规进行研究，并遵守美国匹兹堡大学的办公室，充分认可AALAS / AALAC机构进行动物实验。动物来源包括杰克逊实验室和查尔斯河实验室。所有的动物进行广泛的健康保证通过每个供应商，以及大学，匹兹堡的内部动物卫生监测方案。进行这项研究是根据美国政府使用脊椎动物校长。该计划是与美国农业部注册，并已与公共卫生实验室动物福利处的保证信。

<table border="1"><tbody><tr><th>仪器</th><th>制造商</th><th>目录编号</th></tr><tr><td> Dumonts（SS/45 °角0.2x0.12mm尖，13.5厘米长度） </td><td>精细科学的工具</td><td> 11203-25 </td></tr><tr><td>手术剪（直- 12CM） </td><td>精细科学的工具</td><td> 14068-12 </td></tr><tr><td>止血（曲12.5厘米） </td><td>精细科学的工具</td><td> 13009-12 </td></tr><tr><td> Microscissors（春季剪刀直- 8CM） </td><td>精细科学的工具</td><td> 15000-00 </td></tr><tr><td>钳（0.8毫米尖，弯- 10CM） </td><td>精细科学的工具</td><td> 11050-10 </td></tr><tr><td>缝合卷轴6-0 </td><td>精细科学的工具</td><td> 18020-60 </td></tr><tr><td>缝合4-0 PDSII </td><td>宾夕法尼亚大学兽医</td><td> ETHZ304H </td></tr><tr><td>纱布的4x4 </td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td>棉花尖端涂药</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 30G针</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 23G针</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 3CC针筒</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 5CC针筒</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 10CC的注射器</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 50CC锥形管</td><td>可以通过购买任何全球供应商</td><td></td></tr><tr><td> 1CC注射器W / 25G针</td><td> Fisher Scientific则</td><td> 14-826-88 </td></tr><tr><td> 100 10聚乙烯管材（PE - 10） </td><td> Fisher Scientific则</td><td> 14 - 170 - 12P </td></tr><tr><td> 50聚乙烯管材100`（PE - 50） </td><td> Fisher Scientific则</td><td> 14 - 170 - 12B </td></tr><tr><td> 3路阀</td><td> Fisher Scientific则</td><td> NC9779127 </td></tr><tr><td>手术蓝色垫</td><td> Fisher Scientific则</td><td> 50-7105 </td></tr><tr><td>无菌区敷料</td><td> Fisher Scientific则</td><td> NC9517505 </td></tr><tr><td>磁带卷1" </td><td>公司快递</td><td> MMM26001 </td></tr><tr><td>直边宽口罐（用于鼻锥帽） </td><td> VWR </td><td> 159000-058 </td></tr><tr><td>不锈钢托盘8"× 11" </td><td> VWR </td><td> 62687-049 </td></tr><tr><td>雄性leur锁3路</td><td> VWR </td><td> 20068-909 </td></tr><tr><td>消毒袋3"X8" </td><td> VWR </td><td> 24008 </td></tr><tr><td>消毒袋5"X10" </td><td> VWR </td><td> 24010 </td></tr><tr><td>野生M650显微镜W /热潮立场</td><td>徕卡</td><td></td></tr><tr><td>徕卡IC D数字相机/实时图像</td><td>徕卡</td><td></td></tr><tr><td>从DIGI - MED双酚A - 400分析仪及系统集成商</td><td>微地中海</td><td> SYS - 400 </td></tr><tr><td> TXD - 310（从DIGI - MED传感器） </td><td>微地中海</td><td> TXD - 300 </td></tr><tr><td>电脑</td><td>戴尔</td><td></td></tr><tr><td>热珠仪器消毒柜</td><td> VWR </td><td> 18000-45 </td></tr><tr><td>奥斯特A5的快船瓦特尺寸40刀片</td><td> VWR </td><td> 10749-020 </td></tr><tr><td>循环heatin克垫18x26 </td><td>哈佛</td><td> py872 - 5272 </td></tr><tr><td>直肠温度计</td><td>肯特科学</td><td> RET - 3 </td></tr></tbody></table><table border="1"><tbody><tr><th>试剂</th><th>集中</th><th>制造商</th><th>目录编号</th></tr><tr><td>戊巴比妥钠（Nembutol钠溶液） </td><td> 70mg/kg </td><td>鼓掌</td><td></td></tr><tr><td>丁丙诺啡盐酸</td><td>为0.1mg/kg </td><td>贝德福德实验室</td><td></td></tr><tr><td>乳酸钠林格注射液250毫升输液袋</td><td>巴克斯特</td><td></td><td></td></tr><tr><td> Aerrane（异氟醚） </td><td> 99.9％ </td><td> NLS动物健康</td><td> 105996 </td></tr><tr><td>肝素钠</td><td> 1000U </td><td> Abraxis药厂</td><td></td></tr><tr><td>氯化抑菌钠</td><td> 0.9％ </td><td> Hospira公司</td><td></td></tr><tr><td>乙醇</td><td> 70％ </td><td>药物AAPER </td><td></td></tr><tr><td> Triadine聚维酮碘（优碘） </td><td></td><td>三合会一次性</td><td></td></tr></tbody></table>

fixed volume or fixed pressure: a murine model of hemorrhagic shock

这是常识，严重失血和外伤导致的不利信号事件往往造成的死亡率级联1，2，3，4，5，这些信号事件也可能导致败血症和/或多个器官功能障碍（按付款当日价格计算）6，7，8，9，10是至关重要的，然后进行调查，以便制定更有效的方法，以帮助遭受创伤的患者的免疫功能受到抑制和不利的信号级联的原因。这种固定式压力失血性休克（HS）程序，虽然在技术上具有挑战性，是一个优秀资源调查这些病理生理条件，11，12，13在生物系统评估的进展，即系统生物学使科学界进一步了解复杂的生理网络和蜂窝通信模式14。失血性休克已被证明是一个揭幕这些蜂窝通信模式，因为这涉及到免疫功能的重要工具，15，16，17，18，可以掌握此过程！此过程也可以被用来作为一个固定的数量或固定压力的方法。我们适应这种技术在小鼠模型，以加强在先天免疫和适应性免疫功能的研究，19，20，21，由于他们在小鼠体积小房协提出了独特的挑战。然而，由于许多可用的小鼠品系，这个物种的代表为研究的生物反应空前资源。 HS模型是一个重要的模型研究蜂窝移动通信的模式和系统，如激素和炎症介质系统，危险的信号，即阻尼和PAMP上调的反应，因为它会引起其他形式的冲击，从不同的不同的反应 。22，23 ，24，25转基因小鼠品系的开发和诱导生物制剂来抑制特定的信号，提出了宝贵的的机会，进一步阐明我们了解向上和向下调控的信号转导后出现严重失血，即HS和创伤26，27 ，28，29，30。 有众多的复苏方法与HS和创伤协会（R） 的31，32，33，34只乳酸林格氏液（LR），等于流血量的三倍，固定体积的复苏方法是在此模型中使用研究远程器官损伤和全身性炎症，如内源性机制，35，36，38这复苏的方法被证明是有效评估HS 和创伤38，39影响。

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

失血性休克模型已被一个可靠和可再生资源，促进与炎症和创伤后器官损害相关的信号级联反应的鉴定和了解。本文提供了相关的手术失血性休克小鼠实验过程和机械方​​面的的一步一步的说明。

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, ...

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JoVE Journal

Medicine

24.7K 次观看.  University of Pittsburgh. 失血性休克模型已被一个可靠和可再生资源，促进与炎症和创伤后器官损害相关的信号级联反应的鉴定和了解。本文提供了相关的手术失血性休克小鼠实验过程和机械方​​面的的一步一步的说明。

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

Murine Model of Wound Healing

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.

A murine model of cutaneous wound healing that can be used to assess therapeutic compounds in physiological and pathophysiological settings.

伤口愈合的小鼠模型

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. ...

科研

医学

Measurement of the Pressure-volume Curve in Mouse Lungs

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential phenotypic changes are best assessed by measurement of the changes in lung elasticity. To best understand specific mechanisms underlying such pathologies in mice, it is essential to make functional measurements that can reflect the developing pathology. Although there are many ways to measure elasticity, the classical method is that of the total lung pressure-volume (PV) curve done over the whole range of lung volumes. This measurement has been made on adult lungs from nearly all mammalian species dating back almost 100 years, and such PV curves also played a major role in the discovery and understanding of the function of pulmonary surfactant in fetal lung development. Unfortunately, such total PV curves have not been widely reported in the mouse, despite the fact that they can provide useful information on the macroscopic effects of structural changes in the lung. Although partial PV curves measuring just the changes in lung volume are sometimes reported, without a measure of absolute volume, the nonlinear nature of the total PV curve makes these partial ones very difficult to interpret. In the present study, we describe a standardized way to measure the total PV curve. We have then tested the ability of these curves to detect changes in mouse lung structure in two common lung pathologies, emphysema and fibrosis. Results showed significant changes in several variables consistent with expected structural changes with these pathologies. This measurement of the lung PV curve in mice thus provides a straightforward means to monitor the progression of the pathophysiologic changes over time and the potential effect of therapeutic procedures.

Here we present a protocol to simply and reliably measure the lung pressure-volume curve in mice, showing that it is sufficiently sensitive to detect phenotypic parenchymal changes in two common lung pathologies, pulmonary fibrosis and emphysema. This metric provides a means to quantify the lung&#8217;s structural changes with developing pathology.

在小鼠肺压力容积曲线的测量

In recent decades the mouse has become the primary animal model of a variety of lung diseases. In models of emphysema or fibrosis, the essential ...

Scleral Cross-linking Using Riboflavin and Ultraviolet-A Radiation for Prevention of Axial Myopia in a Rabbit Model

Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal abnormalities. In addition, pathological myopia is a common irreversible cause of visual impairment and blindness1-3. Our study demonstrates the effect of scleral crosslinking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. The axial length of the eyeball was measured by A-scan ultrasound in New Zealand white rabbits aged 13 days (male and female). The eye then underwent 360&#176; conjunctival peritomy with scleral crosslinking, followed by tarsorrhaphy. Axial elongation was induced in 13 day-old New Zealand rabbits by suturing their right eye eyelids (tarsorrhaphy). The eyes were divided into quadrants, and every quadrant had two scleral irradiation zones, each with an area of 0.2 cm&#178; and a radius of 4 mm. Crosslinking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones 20 sec before ultraviolet-A irradiation and every 20 sec during the 200 sec irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm&#178; (total UVA light dose, 57 J/cm&#178;). Tarsorrhaphies were removed on day 55, followed by repeated axial length measurements. This study demonstrates that scleral crosslinking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model.

We demonstrate the effect of scleral crosslinking with riboflavin and UVA on an axial elongation rabbit eye. Axial elongation was induced in 13 day-old New Zealand rabbits (male and female) by suturing their right eye eyelids (tarsorrhaphy).

巩膜交联兔模型使用核黄素和紫外辐射的轴性近视防治

Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal ...

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 ...

Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. Recent technological progress has enabled the fabrication of microelectrode arrays that allow recording the activity of multiple individual neurons in the neocortex of the human brain. These arrays have the potential to bring unique insight onto the neuronal correlates of cerebral function in health and disease. Furthermore, the identification and decoding of volitional neuronal activity opens the possibility to establish brain-computer interfaces, and thus might help restore lost neurological functions. The implantation of neocortical microelectrode arrays is an invasive procedure requiring a supra-centimetric craniotomy and the exposure of the cortical surface; thus, the procedure must be performed by an adequately trained neurosurgeon. In order to provide an opportunity for surgical training, we designed a procedure based on a human cadaver model. The use of a formaldehyde-fixed human cadaver bypasses the practical, ethical and financial difficulties of surgical practice on animals (especially non-human primates) while preserving the macroscopic structure of the head, skull, meninges and cerebral surface and allowing realistic, operating room-like positioning and instrumentation. Furthermore, the use of a human cadaver is closer to clinical daily practice than any non-human model. The major drawbacks of the cadaveric simulation are the absence of cerebral pulsation and of blood and cerebrospinal fluid circulation. We suggest that a formaldehyde-fixed human cadaver model is an adequate, practical and cost-effective approach to ensure proper surgical training before implanting microelectrode arrays in the living human neocortex.

We designed a procedure in which a formaldehyde-fixed human cadaver is used to assist neurosurgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain.

应用甲醛固定人尸体模型植入皮层微电极阵列的外科训练

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. ...

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

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any potential therapeutic approach directed against acute left ventricular (LV) dysfunction. Current imaging modalities (e.g., echocardiography and magnetic resonance imaging) have several limitations since data on LV pressure cannot directly be measured. LV catheterization in mice undergoing coronary artery occlusion could serve as a novel method for a real-time evaluation of LV function.
At the beginning of the procedure, mice were anesthetized followed by endotracheal intubation. For LV catheterization, the right carotid artery was exposed via middle-neck incision. The catheter was introduced and placed into the LV cavity. Left thoracotomy was conducted and the left main coronary artery (LCA) was ligated. To induce reperfusion, the suture was released after 45 min. Pressure-volume data was recorded at all times.
Ligation of the LCA caused a decrease in LV systolic function as evidenced by a 30% reduction in stroke volume, LV ejection fraction (EF), and cardiac output. Maximum dP/dt as a parameter for LV contractility was also significantly reduced and diastolic function was severely impaired (minimum dP/dt -40%). Reperfusion over a period of 20 min did not lead to a complete recovery of LV function.
Real-time pressure-volume analysis served as a valid procedure for monitoring cardiac function during acute myocardial infarction in mice. Maintaining stable anesthesia and a standardized surgical approach was crucial to ensure valid results. As the early phase of acute myocardial infarction is critical for morbidity and mortality, the delineated method could be beneficial for preclinical evaluation of new strategies for cardioprotection.

Acute myocardial infarction in mice induces acute but incompletely characterized changes in left ventricular (LV) function. LV catheterization in mice undergoing coronary artery occlusion serves as a novel method for a real-time evaluation of LV function.

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

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 ...

The Lower Body Positive Pressure Treadmill for Knee Osteoarthritis Rehabilitation

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.

Here, based on a clinician&#8217;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in addition to a clinical, functional assessment methodology, including details for further encouragement of the development of non-drug surgical intervention strategies in knee osteoarthritis patients. However, we only present the effect of LBPP training in improvement of pain and knee function in one patient through three-dimensional gait analysis. The exact, long-term effects of this approach should be explored in future studies.

下体正压跑步机用于膝关节骨关节炎康复

Here, based on a clinician&rsquo;s point-of-view, we propose a two-model lower body positive pressure (LBPP) protocol (walking and squatting models) in ...

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. 
We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. 
The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

Here we present a closed chest approach to admittance-based bi-ventricular pressure-volume loop recordings in pigs with acute right ventricular dysfunction.

猪模型中闭合胸部双心室压力-体积循环记录与导管

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular ...