We would like to give a big thanks to the Visible Heart Laboratory staff and students that have helped with this project: Nate Menninga, Lars Mattison and Megan Schmidt.

该协议被批准明尼苏达机构动物护理和使用委员会的大学。 <img alt="图1" src="/files/ftp_upload/52600/52600fig1.jpg" /> 图1图研究范式的 <a href="https://www.jove.com/files/ftp_upload/52600/52600fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 1.手术猪的制备<ol><li>辖5-7mg / kg的替来他明/ zilazipam的通过肌肉注射猪（70-80公斤）。将耳静脉导管，并通过静脉通道给予5-7毫克/千克美索比妥。插管与气管插管和通风的动物。 </li><li>递送异氟烷&gt; 1.2％的MAC在室内空气和氧气的混合物维持麻醉的手术平面。确保动物在阿耐思特的深面hesia之前，通过检查没有下巴基调，保持最低肺泡浓度高于麻醉猪的任何操作。最初的麻醉深度检查，通过确保无颚音，异氟醚浓度进行的整个过程中（&gt; 1.5 MAC）持续监测，以确保麻醉深面。 </li><li>小心访问与烧灼和钝性分离右颈外和颈动脉。放置一个8.5F Swan-Ganz导管在颈外和膨胀的气球至1.5立方厘米。然后通过右心房穿越，进入心室，并通过肺动脉瓣下肺动脉直到感觉到楔压。 </li><li>放气该气囊和离开所述导管在这个位置。记录使用气球右心房压力和肺动脉压力。此外，记录在肺楔压或压力（或者如果肺部被认为是正常的，则还记录留下了试验压力）。 注意:此导管还允许心输出量的估计。 </li><li>放置一个附加5.0F气球压力导管在颈外并进入右心室连续记录压力。 </li><li>放置在颈动脉中的5.0F气球压力导管，脱出通过主动脉瓣，并在左心室维护。刷新所有压力导管连接到压力换能器20单位/毫升heparanized盐水，并记录从左心室所有的压力数据，右心室（和估计的心输出量），肺动​​脉压和右心房压。 </li><li>对于外围监控，通过将一个导管18F为实时血压，血气监测进入股动脉的分支。在手术过程中记录心脏速率和温度。 </li><li>小心访问与烧灼和钝性分离左侧颈外静脉。将两个11.0F止血引荐的枸骨拉尔安全与0丝线缝合。将导引导管的介绍人。 </li><li>下透视引导，地方主动固定在右心耳和右心室的心尖引线。 注:固定引线，心脏连接到心脏起搏器植入手术植入电线。 </li><li> Connectanalyzer电缆引线并测试利用程序员捕获。设置参数为8V，0.25毫秒的持续时间，并且在最少的比当时的固有速率高10 BPM设置起搏速率。记录为每根引线的相对阻抗。 </li><li>使从剑突内侧外科手术切口的胸锁乳突肌的插入附近。使用胸骨锯，除去从胸骨（龙骨骨）的前突起，以使胸骨的部分内侧清扫。使用通过胸骨骨结构的剩余部分切成一剪切力。解剖胸骨，心包韧带和收回sternu米</li><li>使用钝性分离至心包从胸腔里料分开。使在心包内侧矢状切口（3-5厘米），并在每个角创建具有四方形结缝线一个心包支架（右，左，上，下的网站）。 </li><li>将临时双极率先左心室心尖区放置一个单极暴跌临时起搏导线插入左心耳。 </li><li>安乐死是通过去除深麻醉下的心脏完成的。 </li></ol> 2.筹备电生理监测<ol><li>心脏定位系统。 <ol><li>选择在心脏标测系统的AF研究连接室心外膜双极起搏导线和心外膜导线与鳄鱼夹在接线盒适当的设置心耳。连接心电图和接地焊盘到系统。 </li></ol></li><li>示波器和草刺激。 <ol><li>连接双极左心室起搏导线和单极心房率先突围框连接到电气验证示波器一草刺激。 </li></ol></li><li>程控电刺激。 <ol><li>固定右心房导线和右心室导线的起搏器放置程序员遥测头像放在了心脏起搏器。选择起搏电极刺激（PES）的研究，并设置参数8V;删除所有患者参数。设置起搏持续时间在400毫秒（或300毫秒）设定为8个脉冲。 </li></ol></li></ol> 3. 在原位研究<ol><li>不应期:研究范式。 <ol><li>确定心房不应期（AERP），心房心室节点不应期（AVNERP）和基线心室有效不应期（VERP），并在30分钟和60分钟后化合物/药物/对照处理的心包输送;额外的时间点可以被添加为德IRED。 </li></ol></li><li>不应期:编程器设置。 <ol><li>突发诱导PES研究参数8步（400毫秒或300毫秒），其次是最低300毫秒起搏。降低起搏直到心室/心房（分别）无法收缩。这是从起搏引线的传感说明;从而确定相对不应期。 </li></ol></li></ol><img alt="图2" src="/files/ftp_upload/52600/52600fig2.jpg" /> 图2. EnSiteSystem:AERP，AVNERP和VERP测定 <a href="https://www.jove.com/files/ftp_upload/52600/52600fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="3"><li>参数:相对AF负荷的测定。 <ol><li>维持动物的心脏房颤，1分钟后，允许它继续留在AF长达10分钟: 即在5焦耳震惊直接拨片心房终止AF之前。萨尔瓦多ICIT AF感应到在每个时间点的10倍。请注意，在本研究中。 AF定义为缺乏P波的不稳定节奏。 </li></ol></li><li> AF负担:草刺激和示波器设置。 <ol><li>优化基层刺激的参数有2秒的脉冲持续时间通过急跌起搏导线左心耳（左心耳）提供4赫兹;通过标准的示波器验证这一点。递送单脉冲到LAA诱导的AF。 </li></ol></li></ol> 4.心外植，复苏（移植模型） <ol><li>主动脉根部插管。 <ol><li>仔细解剖周围的升主动脉的心包组织，取出2.0 Ethibond缝合pericardium.Suture两个点（2-3厘米除外）在升主动脉和管理30000台肝素静脉注射。 </li><li>放置缝合点之间的主动脉根部套管和固定主动脉。与加压输送系统，除去叔他口针斜面放置一个夹在插管不允许流量。 </li></ol></li><li>搏准备。 <ol><li>辖150毫米/ Hg的压力下通过加压袋冷圣托马斯心麻痹液进入升主动脉。固定附加到加压停跳与远端的3路活栓的冲洗导管。固定止水栓到主动脉根部插管，通过导管释放停跳的稳定冲洗，并固定在主动脉根部插管。 </li></ol></li><li>交叉夹紧。 <ol><li>夹紧下腔静脉与atraumaticclamp 1-2厘米只是优于隔膜。钳与升主动脉优于主动脉根插管无创伤角度营1-2厘米升主动脉。 </li></ol></li><li>跨钳/搏。 <ol><li>从主动脉根部套管除去夹子，在150毫米/汞柱朝向主动脉瓣冲洗停跳，关闭主动脉瓣和perfusING冠状动脉。 </li><li>钳上腔静脉，并进行小切口在肺动脉，以免过度加压的心脏。一旦心脏停止（asystolic），消费税和从胸部和地点取出心脏在寒冷的Krebs-Henseleit缓冲液的浴（〜3-8°C）。 </li></ol></li><li>复活。 <ol><li>导管插入大血管和利用可见心的方法准备心脏（3）。一旦灌注心脏达到37±5℃，通过经由心外膜贴片电极递送34Ĵ冲击到心室恢复天然窦性心律。 </li></ol></li></ol> 5. 在体外研究范式<ol><li>连续监测60分钟后复苏的心脏功能。连续监测在2D模式下超声心动图与短轴切面:刚二尖瓣低于LV视图。 </li><li>计算心室壁厚度和射血分数每10分钟后复苏（见下文）。在评估期间采取从-5分钟冠状窦（1毫升），并每5分钟样本。 </li><li>监控。 <ol><li>监视左和右心室，包括压力，流量和量的变化两者血液动力学。 </li></ol></li><li>超声心动图:射血分数。 <ol><li>直接放在心脏经胸回声探测，捕获中期乳头短轴观。用公式计算射血分数（EF％）的4室的工作模式，每10分钟:LV舒张末期容积 - 左心室收缩末期容积×100 / LV舒张末期容积</li></ol></li><li>超声心动图:左室壁厚度。 <ol><li>以10分钟的间隔一个小时后复苏测量从一个中期的乳头短轴窗口室壁厚度（厘米）。测量使用屏幕卡尺左心室的四角和取平均。 </li></ol></li><li>心肌代谢。 <ol><li>放置steeraBLE导管冠状窦（CS）。从样品前复活的CS 5分钟，每5分钟后复苏1小时1毫升。测试乳酸盐和葡萄糖水平的样品;其他血液气体也可以被评估。 </li></ol></li></ol>

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The authors have nothing to disclose

这里，我们已经证明用于测试目标递送化合物的潜在功效进入心包空间中的独特的方法。本研究范例可以用于测试目前市场释放药物产品或实验化合物，从而提供了直接的平移应用到各种临床设置。在这一治疗策略有交付药品，心包内的两个主要的临床应用:1）开放式心脏或微创心脏外科手术; 2）心脏移植和器官保存。此外，本研究范例具有可以被分析，以便更好地了解自己这些描述的治疗策略中的药物制剂的预测功效多个参数在原地参数包括:1）的AVN，心房和/或心室的相对不应期; 2）相对AF易感性/负担的决心;和3）hemodynam。集成电路和心脏速率响应体外的参数包括:1）相对于射血分数; 2）LV壁厚反应; 3）心脏代谢改变; 4）血流动力学和心脏率的变化。我们在座的历史数据表明选择这些描述的参数。这些研究的最显着的平移方面是用于开启或微创心脏手术，以及移植前脏器采购。 更具体地，所形成的心包支架的开放式心脏外科手术中放置，或者微创或以下全胸骨切开术，提供了施用局部化合物的重要机会:即，在较高的浓度比可以静脉内和/或无全身副作用施用影响。甚至微创心脏手术（ 例如 ，subxyphoid接入），一个小的切口以可能也被用作靶药物输送的导管心包制成。 MYOC而心脏则在各种心脏手术操纵ardial烦躁/侮辱大大提高。直接治疗心律失常和/或功能障碍可以是用于改善患者的治疗效果的有益和容易的装置。 类似的应用可能在器官恢复过程可以容易地进行，例如，心脏采购之前预处理。至关重要的是，在心肌最佳地调节为包括移植后除颤的心脏返回到正常的窦性心律一个复杂的过程。换句话说，有在心脏的采购和移植后增加心房和心室性心动过速和/或纤维性颤动的危险。另外，采购过程中，其中外周施用药物可危及这些器官保存在供体的其他器官是重要的。例如，静脉内施用美托洛尔可导致急性肾dysfuncti鉴于在手术过程中治疗心律失常时/采购1。目前，心脏必须在大约4-6小时被移植到收件人。此时约束保持为今天执行心脏移植的限制因素之一。因此，采用的实验范例，我们在这里描述可以用于评估可能是在器官恢复后延长的局部缺血时间可接受的范围内有益的化合物的重要手段。 从利用该研究范例我们实验室以前收集的数据表明，它可以用于获得可以被分析以预测药剂的所描述的治疗策略中的功效本身多个参数非常有用的。更具体地说，研究有效不应期以下心包交付DHA，DHA输液，倍他乐克等药物在原地一直重要的，所以要了解他们的一个此目标交付方式ntiarrhythmic潜力。延长有效不应期和/或降低的AVN内的电导速度通常可以终止某些类型的心律不齐4。此处作为对照相比（先前公布的，1我们已经证明，在以下一个DHA输注这些有效不应期，以及递送美托洛尔后显着增加。另外，感兴趣的是确定，因为它向关系的相对AF负荷对于在给定患者心律失常增强的概率;在这里，我们也注意到以下的药理预处理在此响应的改变。 预处理的心脏的复苏后的临床相关临床指标的调查也给翻译见解，这种药物给药对接受移植者的潜在利益。迄今为止，使用此总目标交付/ preconditioning研究方法，我们的实验室已调查了各种临床施用试剂以及新药理化合物可能最小化心律失常或缺血性损伤的心脏（美托洛尔，胺碘酮，利多卡因，δ-阿片类，ω-3脂肪酸，ursodyoxycholic酸，lipovenous ，十二碳六烯酸和/或这些的组合）。还应当指出的是，这些试剂也可以作为内描述的方案的体外方面调理后剂施用。观察在体外血流动力学，为LV压力代表数据是在已经用DHA或一个DHA滴注相比的车辆用控制心明显更高。此外，我们的实验室已观察到在射血分数和LV壁厚度变化在处理的心脏相比对照。可以研究的临床参数/因素是重要的，所以，以评估有效的功能，并观察水肿的发作。 Furt例如 ，乳酸盐和葡萄糖水平:她的，也可为各种代谢因素分析得到从冠状窦样品。这些参数是必要的，以评估相对于心脏代谢和/或整体心脏功能。例如，增加乳酸水平往往是指示性酸中毒，进而导致心脏功能不好。 我们从这些研究获得的数据表明一个可行的实验模型（用，因为该研究的急性性质注意到限制），以确定利用或者临床上可用的药物或实验试剂的心包目标传递策略的实用性。我们认为，我们在这里描述的调查方法是高度可再现，并提供了相对于目标和各种药理学药剂的心包空间内的输送的全身好处新的见解。结果人们可以得到这样的设计方案可以有祁门功夫，功夫为心脏手术和心脏移植坦平的影响。

目前在开放式心脏手术，医生使用抗心律失常等治疗药物全身。然而，这可能是许多患者，特别是那些谁已经在临床上损害问题。例如，静脉内治疗可导致血压或肾功能不全的全身滴;进一步，它们可以创建麻醉管理问题和/或其它长期副作用。 在这里，我们创建了一个模型来测试药物给药制剂进入心包空间的功效。例如，这种方法可用于测试抗心律失常药物，研究可能增加心脏功能和/或外科手术后的心肌的促进恢复化合物。已经有目标交付的治疗进入心包腔与静脉给药观察的优点: 例如 ，我们的实验室证明antiar的本地化交付节奏的药物，如美托洛尔，是针对心律失常的发生保护，同时尽量减少在血压1降低。这一目标的投放策略也提供了更高的管理焦点浓度，同时尽量减少系统水平的机会。例如，高含量的脂肪酸静脉内递送的浓度可能会导致溶血，但是心包输送最小化这一问题2。 本研究范例包括三个主要的目标，以确定心包递送化合物的功效:1） 在原位测定心房心室节点的不应期，心房和心室，治疗前和30分钟和60分钟后处理的; 2）相对治疗 30和60分钟后处理（经常被添加额外的时间点），它已被重新加进3 INC后的心脏3）功能分析之前， 现场 AF负担泸定血流动力学监测，心脏率，从冠状静脉窦采样心脏代谢（乳酸和葡萄糖），射血分数（EF％）和室壁厚度（厘米）来监控每10分钟后复苏这一治疗策略模型使我们能够观察到的影响药剂可以减少期间和心脏手术或移植后心律失常和/或缺血性损伤的发生率。

<table><tbody><tr><td>SelectSecure 3830 lead</td><td>Medtronic</td><td></td><td>Pacing Lead&amp;nbsp;</td></tr><tr><td>C304 Deflectable Catheter&amp;nbsp;</td><td>Medtronic</td><td></td><td>Steerable catheter for placing leads&amp;nbsp;</td></tr><tr><td>SelectSecure 3830 lead</td><td>Medtronic</td><td></td><td>active fixation pacing leads&amp;nbsp;</td></tr><tr><td>Grass S48 Stimulator</td><td></td><td></td><td>Electrical Stimulator&amp;nbsp;</td></tr><tr><td>Premium 6500 Unipolar Pacing&amp;nbsp;</td><td></td><td></td><td>Plunge pacing lead for LAA</td></tr><tr><td>EnSite Cardiac Mapping</td><td></td><td></td><td>Electrophysiology mapping system</td></tr><tr><td>CareLink Programer 2092</td><td>Medtronic</td><td></td><td>programmer for pacing leads</td></tr><tr><td>GEM II pacemaker&amp;nbsp;</td><td>Medtronic</td><td></td><td>pacemaker can&amp;nbsp;</td></tr><tr><td>DLP Aortic Root Cannula</td><td>Medtronic</td><td></td><td>aortic root cannula for transplant&amp;nbsp;</td></tr><tr><td>C-Arm Fluoroscopy</td><td>Ziehm&amp;nbsp;</td><td></td><td>fluoroscopic imaging&amp;nbsp;</td></tr><tr><td>Oscilliscope</td><td>Tektronix&amp;nbsp;</td><td></td><td></td></tr><tr><td>11F Hemostasis introducer</td><td>SafeSheath</td><td></td><td>Hemostasis introducers</td></tr><tr><td>Swan-Ganz Catheter 8.0F</td><td>ICU Medical&amp;nbsp;</td><td></td><td>thermal dilution catheter&amp;nbsp;</td></tr><tr><td>Venogram balloon&amp;nbsp;</td><td>Oscor</td><td></td><td>pressure monitoring&amp;nbsp;</td></tr><tr><td>Ultraview SL</td><td>Spacelabs</td><td></td><td>EKG and blood pressure&amp;nbsp;</td></tr><tr><td>s/5 Avance</td><td>General Electric</td><td></td><td>Anesthesia machine</td></tr><tr><td>Atrial 6492 &amp;ndash; Unipolar Temporary Atrial Pacing Lead</td><td>Medtronic</td><td></td><td>temporary pacing lead&amp;nbsp;</td></tr><tr><td>VIVID i</td><td>General Electric</td><td></td><td>2D electrocardiography unit&amp;nbsp;</td></tr></tbody></table>

testing the efficacy of pharmacological agents in a pericardial target delivery model in the swine

迄今为止，许多药剂用于治疗或预防心脏直视例心律失常创建不希望的全身性副作用。例如，静脉内给予抗心律失常药物可以产生全身性的压降在已经受损的心脏的病人。在执行开放式心脏手术，外科医生通常要么创建一个小口或形成心包支架创造适宜的操作领域。此为目标的药理递送（抗心律不齐或缺血预处理剂）直接连接到心肌组织而不不良副作用访问收益的机会。 我们已经制定了心包液中测试药物制剂为目标交付猪模型。而完全麻醉，每只动物用Swan-Ganz导管仪器以及左和右心室压力导管和起搏引线置于右心耳和右心室。然后进行内侧胸骨和心包访问摇篮创建的;暴跌起搏导线被放置在左心耳和双极起搏引线放置在左心室。利用程序员和心脏标测系统，房室结（AVN）的不应期，心房和心室测定。此外，制作心房颤动（AF）利用诱导房颤一个草刺激和时间进行了观察。这些测量被处理，以及30分钟和心包治疗后60分钟之前进行。对选定的研究中加入额外的时间点。随后心脏被cardiopleged并在四室的工作模式重新加进的。压力测量和功能进行了记录复苏后1小时。此治疗策略模型使我们能够观察药理学试剂的可能降低期间​​和AF心律失常和/或缺血性损伤，发生率的影响之三心脏直视手术。

这些结果是可利用在猪的药理学试剂的这个目标传递模型要收集的数据的特性。此数据显示在下面的一个DHA输液原位这些心室有效不应期（VERP）显着增加。此外，该数据确立了较体外控制的DHA左心室压力的增加。相比于在几个时间点控制在DHA处理的心脏的左心室压力均显著高。该数据证实了原位和体外试验治疗策略药理窗口。 <img alt="图3" src="/files/ftp_upload/52600/52600fig3.jpg" /> 图3.心室有效不应期（VERP）变化。心室有效不应期（VERP）测定5分钟控制股份公司的心包分娩前耳鼻喉科（盐水）或二十二碳六烯酸（DHA），或DHA输液，除了30分钟和60分钟后的心包递送的任一的治疗或控制。在DHA组VERP走向与对照组相比增加趋势。 <a href="https://www.jove.com/files/ftp_upload/52600/52600fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图4" src="/files/ftp_upload/52600/52600fig4.jpg" /> 图 4. 4室工作模式的最大压力（毫米汞柱） 压力左心室确定每5分钟60分钟的心脏是使用可视心脏方法重新加进了。 DHA和DHA输注（对于在10分钟内处理的）处理的心脏趋于引起初始比为广大的测试期间的控制更高的压力。一个未配对t检验完成FOr各自时间点。 （*，P = 0.065，+，P = 0.056，†，P = 0.059‡P = 0.058）， <a href="https://www.jove.com/files/ftp_upload/52600/52600fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 心室有效不应期（VERP）测定心包递送控制剂（盐水）或二十二碳六酸（DHA），或DHA输注（在10分钟），除30和60分钟后的心包递送的前5分钟或在治疗或控制。 DHA的组的VERP朝向增加与对照相比趋势。 最大压力（毫米汞柱），每5分钟测定60分钟的心脏是使用可视心脏方法重新加进了。 DHA和DHA输液治疗的心脏趋于引起初始比为广大的测试期间的控制更高的压力。一个未配对t检验完成为每个时间点。 （*，p = 0.065，+ P =0.056，†，P = 0.059‡P = 0.058）

Watch this Scientific Journal Video about Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine at JoVE.com

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine

We have developed a swine model for the target delivery of pharmacological agents within the pericardial space/fluid. Using this approach, the relative benefits of administered agents on induced atrial fibrillation, relative refractory periods and/or ischemic protection can be investigated.

药理试验药物的疗效在心包目标交付模型在猪

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, ...

testing-efficacy-pharmacological-agents-pericardial-target-delivery

Nanyang Technological University

Research

Education

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JoVE Journal

Pharmacology

Medicine

Unit 1

Cardiovascular Drugs: Antiarrhythmic and Heart Failure Drugs

SCIENTISTS IN ACTION

8.2K 次观看.  University of Minnesota. We have developed a swine model for the target delivery of pharmacological agents within the pericardial space/fluid. Using this approach, the relative benefits of administered agents on induced atrial fibrillation, relative refractory periods and/or ischemic protection can be investigated. 

视频: Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

心肌梗死和功能预后评估的猪

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

科研

医学

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies.
There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

The purpose of this protocol is to demonstrate the placement of a delayed constricting device (an ameroid constrictor) around a coronary artery in a swine model. This device creates an ischemic area of the heart that is useful for studying new diagnostic imaging techniques and new methods of treatment.

应用 Ameroid 的猪慢性心肌缺血模型

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

Percutaneous Contrast Echocardiography-guided Intramyocardial Injection and Cell Delivery in a Large Preclinical Model

Cell and gene therapy are exciting and promising strategies for the purpose of cardiac regeneration in the setting of heart failure with reduced ejection fraction (HFrEF). Before they can be considered for use, and implemented in humans, extensive preclinical studies are required in large animal models to evaluate the safety, efficacy, and fate of the injectate (e.g., stem cells) once delivered into the myocardium. Small rodent models offer advantages (e.g., cost effectiveness, amenability for genetic manipulation); however, given inherent limitations of these models, the findings in these rarely translate into the clinic. Conversely, large animal models such as rabbits, have advantages (e.g., similar cardiac electrophysiology compared to humans and other large animals), whilst retaining a good cost-effective balance. Here, we demonstrate how to perform a percutaneous contrast echocardiography-guided intramyocardial injection (IMI) technique, which is minimally invasive, safe, well tolerated, and very effective in the targeted delivery of injectates, including cells, into several locations within the myocardium of a rabbit model. For the implementation of this technique, we also have taken advantage of a widely available clinical echocardiography system. After putting in practice the protocol described here, a researcher with basic ultrasound knowledge will become competent in the performance of this versatile and minimally invasive technique for routine use in experiments, aimed at hypothesis testing of the capabilities of cardiac regenerative therapeutics in the rabbit model. Once competency is achieved, the whole procedure can be performed within 25 min after anaesthetizing the rabbit.

Novel therapeutic strategies in cardiac regenerative medicine require extensive and detailed studies in large preclinical animal models before they can be considered for use in humans. Here, we demonstrate a percutaneous contrast echocardiography-guided intramyocardial injection technique in rabbits, which is valuable for hypothesis testing the efficacy of such novel therapies.

经皮超声心动图引导心肌注射液与大鼠前体细胞的临床研究

Cell and gene therapy are exciting and promising strategies for the purpose of cardiac regeneration in the setting of heart failure with reduced ejection ...

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved drug to prevent or reduce myocardial I/R injury. The study and understanding of the pathophysiological mechanisms of myocardial I/R injury is essential to develop successful treatments. Large animal experiments are an important step in translational methods. The porcine model of acute myocardial infarction has been established and described by ourselves and others. We aimed to further improve the value of the model by focusing in detail on the sampling techniques for use in future experiments. Furthermore, we emphasize small but important steps that can affect the quality of the final results. To mimic the clinical situation of myocardial I/R injury, a percutaneous coronary intervention (PCI) catheter was inserted into the left anterior descending coronary artery (LAD) of an anesthetized pig. &#176;&#176;&#176;This model mimics acute myocardial infarction and PCI treatment in humans with the possibility of accurately determining the area at risk as well as the necrotic- and viable ischemic tissue. Here the model was used to investigate the effect of a bicyclic peptide inhibitor of FXIIa. The model can also be modified to allow longer reperfusion times to study later effects of myocardial infarction.

Here we demonstrate a protocol to standardize sampling procedures of an established porcine model of acute myocardial infarction in order to increase its translational value in the understanding of the pathophysiology of myocardial ischemia/reperfusion injury and to test novel drug candidates.

组织和采血程序标准化改善闭合性胸猪心肌梗死模型的研究

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved ...

Standardized Model of Ventricular Fibrillation and Advanced Cardiac Life Support in Swine

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as preclinical settings. Prospective randomized trials in human subjects are difficult to design and ethically ambiguous, which results in a lack of evidence-based therapies. The model presented in this report represents one of the most common causes of cardiac arrests, ventricular fibrillation, in a standardized setting in a large animal model. This allows for reproducible observations and various therapeutic interventions under clinically accurate conditions, hence facilitating the generation of better evidence and eventually the potential for improved medical treatment.

Cardiopulmonary resuscitation and defibrillation are the only effective therapeutic options during cardiac arrest caused by ventricular fibrillation. This model presents a standardized regimen to induce, assess, and treat this physiological state in a porcine model, thus providing a clinical approach with various opportunities for data collection and analysis.

猪心室颤动和高级心脏生命支持标准化模型

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as ...

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

We describe a novel, cost-effective, and efficient technique for percutaneous delivery of three-dimensionally printed coronary implants to create closed-chest swine models of ischemic heart disease. The implants were fixed in place using a mother-and-child extension catheter with high success rate.

在缺血性心脏病的猪模型中部署3D打印冠状动脉狭窄植入物的新颖的皮下方法

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally ...

Measuring Cardiac Output in a Swine Model

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume and cardiac output are essential in this type of research. Contrast ventriculography, thermodilution, and pressure-volume loop (PV-loop) catheters can be used to accurately obtain cardiac performance data depending on which resources and expertise are available. For this study,five Yorkshire swine were anesthetized and intubated. Central venous and arterial access was obtained to place the necessary measurement instruments.A temperature probe was placed in the aortic root. A cold saline bolus was delivered to the right atrium and temperature deflection curve was recorded. Integration of the area under the curve allowed for the calculation of the current cardiac output.A pigtail catheter was percutaneously placed in the left ventricle and 30 mL of iodinated contrast was power injected over 2 seconds. Digital subtraction angiography images were uploaded to volumetric analysis software to calculate the stroke volume and cardiac output. A pressure volume-loop catheter was placed into the left ventricle (LV) and provided continuous pressure and volume data of the LV, which allowed the calculation of both stroke volume and cardiac output.All three methods demonstrated good correlation with each other. The PV-loop catheter and thermodilution exhibited the best correlation with a 3% error and a Pearson coefficient of 0.99, with 95% CI=0.97 to 1.1, (p=0.002). The PV-loop catheter against ventriculography also showed good correlation with a 6% error and a Pearson coefficient of 0.95, 95% CI=0.96 to 1.1 (p=0.01). Finally, thermodilution against ventriculography had a 2% error with r=0.95, 95% CI=0.93 to 1.11, (p=0.01). In conclusion, we state that the PV-loop catheter, contrast ventriculography, and thermodilution each offer certain advantages depending on the researcher's requirements. Each method is reliable and accurate for measuring various cardiac parameters in swine such as the stroke volume and cardiac output.

<meta charset="utf8"></head><body>在猪模型中测量心输出量

Thermodilution, pressure-volume loop catheters, and contrast ventriculography are reliable and accurate methods for determining cardiac physiology such as stroke volume and cardiac output in a laboratory setting in swine.

在猪模型中测量心输出量

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume ...

Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only target the electrical abnormalities and not the underlying atrial myopathy. For the development of novel therapies, a reproducible large animal model of atrial myopathy is necessary. This paper presents a model of sterile pericarditis-induced atrial myopathy in Aachener minipigs. Sterile pericarditis was induced by spraying sterile talcum and leaving a layer of sterile gauze over the atrial epicardial surface. This led to inflammation and fibrosis, two crucial components of the pathophysiology of atrial myopathy, making the atria susceptible to the induction of AF. Two pacemaker electrodes were positioned epicardially on each atrium and connected to two pacemakers from different manufacturers. This strategy allowed for repeated non-invasive atrial programmed stimulation to determine the inducibility of AF at specified time points after surgery. Different protocols to test AF inducibility were used. The advantages of this model are its clinical relevance, with AF inducibility and the rapid induction of inflammation and fibrosis-both present in atrial myopathy-and its reproducibility. The model will be useful in the development of novel therapies targeting atrial myopathy and AF.

We describe a sterile pericarditis model in minipigs to study atrial myopathy and atrial fibrillation (AF). We present surgical and anesthetic techniques, strategies for vascular access, and a protocol to study the inducibility of AF.

Aachener Minipigs的无菌性心包炎作为心房肌病和心房颤动的模型

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only ...

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Myocardial infarction (MI) animal models that emulate the natural process of the disease in humans are crucial to understanding pathophysiological mechanisms and testing the safety and efficacy of new emergent therapies. Here, we describe an MI swine model created by deploying a percutaneous embolization coil.

猪模型中经皮栓塞线圈部署的心肌梗死

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization ...

药理试验药物的疗效在心包目标交付模型在猪

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在猪模型中测量心输出量

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