Name: primary outcome assessment in a pig model of acute myocardial infarction
Uploaded: 2016-10-14T15:00:00.000+00:00
Duration: 14 min 19 s
Description: Watch this Scientific Journal Video about Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction at JoVE.com

The authors gratefully acknowledge Marlijn Jansen, Joyce Visser, Grace Croft, Martijn van Nieuwburg, Danny Elbersen and Evelyn Velema for their excellent technical support during the animal experiments.

所有的动物实验是由伦理委员会对大学医学中心的乌得勒支动物实验（荷兰乌得勒支）批准，并符合"指南照料和使用实验动物的"。 注:协议来执行闭胸气囊遮挡不是当前手稿的一部分，并在别处详细5进行说明。总之，猪（60 - 70公斤）进行左前降支（LAD）的中央部的75分钟腔内球囊闭塞。 既，三维食管超声心动图（3D-TEE）和压力 - 体积（PV）循环测量可以在基线，短期和长期随访进行。注意，这些测量被认为是在心肌梗死后的第一个小时内不可靠，由于在此阶段频繁心律失常。心肌梗死面积（IS）和面积有风险（AAR）测量preferablŸ评估在短期随访（24 - 72小时）15,16，由于微血管和二级心肌疤痕变薄变化不太可靠的结果告终。梗塞大小染色是使用2,3,5-氯化三苯基四唑（TTC）（注意，刺激物），这被认为是高度可再现的和相对廉价的进行。 TTC是毫无色彩溶解在盐水中的白色粉末。在与各种脱氢酶接触，它被转换为一个砖红色。由此，判别活（红）和死心肌组织（白色）之间。有关这两种侵入性和非侵入性梗塞面积确定的概述，读者可以直接进行全面审查关于这个问题的17。 图1示出的时间线包括麻醉，手术准备和在该研究中使用的主要成果的测量。 1.药物和麻醉<ol><li>确保动物不吃或喝之前的过程至少5小时。前处理，麻醉和手术后疼痛的治疗方案已在别处详细5进行了描述。 </li><li>总之，手术前一天的一buprenorfine补丁（5微克/小时）被施加到处于活动七天，以限制手术后疼痛的皮肤。在手术当天，稳重猪由0.4毫克/千克咪达唑仑，10毫克/千克氯胺酮和0.014毫克/千克阿托品肌肉注射。等待约10 - 15分钟。在耳脉之一插入18G的套管和管理5毫克/公斤钠硫喷妥钠诱导麻醉。 </li><li>插管使用气管插管（为60头猪大小8.5 - 70公斤）猪。如果需要的话，则执行气球通气（频率12 /分钟）和运输猪到手术室。 </li><li>一旦在操作到达战区，开始机械正压通气与氧合指数2 0.50 10毫升/公斤潮气量和使用连续的一个12 / min的频率二氧化碳监测记录。 </li><li>通过咪达唑仑的组合（0.5毫克/千克/小时），舒芬太尼（2.5微克/千克/小时）和泮库溴铵（0.1毫克/千克/小时）的连续静脉输注开始平衡麻醉。 </li><li>通过测试角膜反射及监测呼吸模式确认麻醉（ 例如 ，机械通气相结合的自主呼吸表明不完全麻醉）。使用对眼睛兽医药膏，以防止干燥而动物处于麻醉状态。 </li></ol> 2. 3D食管超声心动图（TEE） <ol><li>要允许心脏速率监控和数据采集，连接动物到5带领超声心动图检查机器上的心电图。 </li><li>放置在右侧卧位的动物。确保探针是通过解锁操作件的直链和柔性的小费。 </li><li>打开猪的嘴，小心地插入食管回声探测。如果有必要，使用visua喉镜补肾中药。要小心，以避免在正常解剖咽囊结束了，类似于食管憩室18。 </li><li>将50探头 - （从吻端尖测量）60厘米。缓慢旋转的探针和头部弯曲到左外侧位置形象化心脏（ 图2A - B）。确保所有的墙都清晰可见。 </li><li>使用超声机的显示屏上的"3D全卷 "选项， 如图2C显示左心室两个垂直图像- D然后最大化正在通过选择"FV选卷"中获取的扇区宽度。通过暂时关闭机械通气，按"采集"来获得完全的体积测量暂停通风。 </li><li>回波采集后，确保尖端是解锁操作件灵活。然后慢慢从动物取下探头。 注意:不要离开日Ë动物无人看管，直到它已经恢复了足够的意识，以保持胸骨斜卧。不要返回已动过手术，以公司的其他动物，直到完全康复的动物。 </li><li>如前面所述的19与验证软件进行离线分析。 </li></ol> 3.基于纳 - 压力 - 容量环采集<ol><li>预浸泡7 F四极导纳导管的感测提示在0.9％盐水（室温至37℃）至少20分钟，以确保在实验20中适当的水分和最小的基线压力漂移。 </li><li>如第1节管理药物和麻醉。 </li><li>进行手术准备和前面5所描述获得的血管通路。 <ol><li>总之，刮胡子，清洁颈部。消毒用碘2％手术区并覆盖用无菌手术单猪的非无菌部分。 </li><li>使在颈部内侧切口，以暴露颈动脉和颈内静脉。插入8 F鞘进入颈动脉和一个9 F鞘进入颈静脉。 </li></ol></li><li>通过在颈静脉的9 F鞘插入的Swan-Ganz导管（SG）导管，并通过在导管的尖端膨胀球囊楔它在一个小肺动脉。在肺的外周部适当放置后，放气的气球。神光连接到外部心脏输出设备。 </li><li>附上包含0.9％的无菌盐水以连接到管腔与最接近河口注射端口20毫升注射器。测量加入5ml 0.9％盐水（室温）的快速输液心输出量，将获得心脏费率来计算每搏输出量（SV）。重复此步骤三次，取其平均值SV。 注:心输出量是（自动地）使用斯图尔特汉密尔顿热稀释方程计算，并且基于在温度变化在室温21生理盐水输液肺动脉。 </li><li>取下导管SG。通过在上下腔静脉颈静脉和它的位置9楼鞘插入8 F导管福格蒂。 </li><li>校准用" 场 "和" 精细 "按钮光伏循环导管的压力信号，而尖端保持在0.9％的盐水。然后输入所测量的SV到系统中。 </li><li>通过在颈动脉中的8 F鞘前进光伏循环导管和在透视下左心室（LV）的居中的顶端。 </li><li>经密谋反对的压力信号的原始电导信号选择最大充分放置段。确保压力电导循环是矩形形状的。相位信号预计将显示3和5度之间用值的窦跟踪。暂停通风和执行基线扫描到电导转换成卷。 <ol><li>接受基准数据按下" 继续 "时的信号是稳定的（无心律失常），心脏速率等于心电图或压力衍生心脏速率和收缩末期（ES）/舒张末期（ED）电导由系统20被适当地感测。 注:后者可以通过绘制对压力信号的原始电导信号和比较从基线衍生的ES / ED电导值扫描到实时电导进行验证。如果任何上述要求没有满足，重复上述步骤。 </li></ol></li><li>通过暂停通气呼吸暂停12次连续 - 通过记录10获得基线压力容积环。 </li><li>充气透视引导下，福格蒂导管，以减少负荷和记录10 - 如上所述，连续12次。确保收缩压保持&gt; 60毫米汞柱和无心律失常与干扰测量。 </li><li>取出福格蒂和PV环导管。保持记录动脉PRESSUR之前和除去光伏循环导管的期间E要启用修正压力漂移（ 即， 离体前后的程序基线压力差）。 注意:不要离开无人看管的动物，直到它已经恢复了足够的意识，以保持胸骨斜卧。不要返回已动过手术，以公司的其他动物，直到完全康复的动物。 </li><li>执行几何测量和验证与22软件功能参数进行离线分析。 </li></ol> 4.区域在风险（AAR）和梗死面积（IS）定量<ol><li>溶解在50毫升0.9％盐水1.00克伊文思蓝（小心23，中毒性），分别填充两个50毫升的路厄锁注射器用20毫升和30毫升2％伊文思蓝溶液，并保持在室温下。 注:在通风橱工作，并佩戴防尘面具，以限制暴露于有害粉尘和使用手套和防护眼镜，以防止接触FR嗡皮肤和眼睛。 </li><li>采取类似的预防措施，溶于37℃的0.9％生理盐水1％2,3,5-三苯基tetrazoliumchloride（TTC）（注意，刺激物），并保持在37℃。 </li><li>手术准备的动物获得的血管通路既颈动脉。执行胸骨切开，以允许在体内 Evans蓝输注5的效果直接可视化。 </li><li>插入一个7 F和在各自的颈动脉的8 F引入鞘。可替代地，在一个单颈动脉插入两个导引鞘或使用股动脉中的一个为两个引导导管中的一个。 </li><li>连接两个标准的Y型连接器，一个7 F JL4和8 F JL4分别导引导管。对于股的方式，使用JR4为右冠状动脉（RCA）和左冠状动脉主干一个JL4（LCMA）。连接10厘米的延长到两个Y型连接器的附加三通旋塞。 </li><li>辖100 IU / kg的肝素。在8 F JL4指导CA的位置theter在通过两个导引鞘中的一个的左主干的口。 </li><li>用0.014"导丝，推进冠状动脉扩张导管通过导管LCMA在其中MI诱导过程中进行冠状动脉闭塞的部位气球的位置。但不要夸大。 </li><li>通过第二导引鞘在RCA的口第二个8 F JL4导引导管位置。 </li><li>通过在透视下注入造影剂，以确认这两个导引导管的正确定位和在冠状动脉中的气球，使用前后和LAO 30°次执行冠状动脉造影（CAG）。 </li><li>附加含有30毫升（LCMA）和20毫升（RCA）的2％伊文思蓝向附着在引导导管的Y连接器的各个三通抽头的50mL的注射器中。 </li><li>充气气球，并确认由CAG冠状动脉闭塞。只有当气球完全阻断任何造影剂的通道，注入伊文思蓝ð靠着而气囊膨胀都导引导管（5毫升/秒）。 </li><li>伊文思蓝灌注完成后直接通过放置一个9伏电池对心脏的非梗死引起部分心室颤动。 </li><li>切开腔静脉以释放压力，并确保抽吸单元可用，以允许血液引流。 </li><li>放气气球，既引导导管一起收回，并通过解剖周围的膜外植体心脏。通过大血管（ 即主动脉，肺动脉/静脉）切的横向允许完整的外植。迅速洗掉血液和多余染料上的外表面，然后使用0.9％盐水中的心腔。 </li><li>小心解剖左心室和从顶点使削减5相等厚10毫米的部分至基部，平行于房室沟的平面。 </li><li>拍摄分别在环境光条件下的所有五个切片的两侧，作为一个可能的伊文思蓝的洗脱可在随后的步骤进行。为了校准，确保一把尺子出现在影像中。 </li><li>孵育在37℃下在1％TTC溶液10分钟，5分钟为等于染色后扭转的部分。 </li><li>此外，拍摄所有五个片的两侧分别在环境光线条件，并确保一个标尺标定图像中可视化。 </li><li>权衡所有切片。适合分析5使用的软件。当使用ImageJ（1.47版），点击"直线"按钮。现在，绘制与图像（ 例如 ，5厘米），在用标尺已知距离的直线。点击"分析" - &gt;"设置规模"，并在框中输入距离"已知的距离"。这个过程允许在像素长度的SI单位距离的校准。 </li><li>使用"多边形选择"按钮，选择对应于左心室心肌在目前IM总面积年龄，单击"分析" - &gt;"办法"获得测量结果。执行此过程对心肌的每个切片的两侧，和每个切片的平均值。 <ol><li>通过切片成比例的所有五个切片的总重量的重量相乘并平均这些测量结果用于所有切片。 </li></ol></li><li>在风险（AAR）和梗死面积（IS）执行的区域类似测量。鸿沟/ AAR，AAR / LV和IS / LV和100％乘以以获得相应结果的测量5。 </li></ol>

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The authors have nothing to disclose.

心脏重塑在很大程度上取决于心肌梗死面积和心肌梗死的质量修复6,26。评估以标准化的方式前，本手稿提供伊文思蓝与体外 TTC染色，已验证和广泛使用8,16,27,28联合体内输注优雅方法。这种方法允许在危险中（AAR）就AAR 16的区域的量化和梗塞大小。目前的做法降低了染料扩散到AAR，梗塞区域或风险 - 与malpositioning - 乳头肌的，因为它不要求心肌穿刺。此外，也没有必要对冠状动脉，这可能是不精确的，不准确的和偶然损坏心肌的外部连接。一种替代的方法，基于导管的Evans蓝输注组合到升主动脉29 &lt;的LV和交叉夹紧/ SUP&gt;，是不可取的原因不同。夹紧闭塞左心室导引导管，阻碍了伊文思蓝灌注进了LV。另外，压缩和牵引力可能导致LCMA导管和冠状动脉内球囊malpositioning和不准确的AAR测量。此外，由于在LAD的球囊阻塞需要在LCMA导引导管的定位，从LV冠状动脉充盈受限，从而防止从LV Evans蓝进入冠状动脉。 然而，虽然优于心肌穿刺和升主动脉的交叉夹持，在该手稿提出的技术需要一些预防措施。需要防止通过阻碍引导导管完全闭塞（之一）冠状动脉。这可以通过监测洗出率和压力来控制，并且通常可以通过从冠状动脉口的略微缩回引导导管被避免。如果不可避免，缩短时间的GUIDING导管定位在冠状动脉尽可能多由制备该协议的其他部分。此外，确保气囊完全闭塞之前，伊文思蓝输液靶血管。 当完成Evans蓝输注，诱导音频和切开腔静脉释放，以防止Evans蓝扩散到AAR气囊放气和导管撤出之前血压。应注意到引导导管中的冠状动脉口轻轻但牢固地定位，从而允许在LAD和回旋支两伊文思蓝的扩散。此外，伊文思蓝输注速率不应过高，因为流动限制到冠状动脉可能导致伊文思蓝洗出进入全身循环。虽然选择性注入冠状动脉，Evans蓝扩散进入全身循环不能完全防止。因此，其他的非心脏组织的组织学分析（ 例如 ，spleeN，肾）仍可能存在问题。同时TTC共同输注到AAR的之前已经描述的，但是我们认为不希望的，因为TTC不到达AAR的由气囊阻塞的部分。此外，以前的分析表明，TTC可能与残留的血管内的血液中的梗死区反应，并用红色在非梗塞AAR 30重叠。这种技术的未来的应用可能是通过阻碍血流进入体循环以保持非心脏组织中。这可以通过胸降主动脉的气球阻塞通过股骨的方式来实现。 超声心动图至今仍然是心血管研究在临床护理和各种动物模型心脏功能评估的基石。然而，由于长白猪的胸椎形状，经胸超声心动图（TTE）是有限到低压9的2维长期和短轴意见。因此，心脏VOLU我和LVEF必须通过数学近似，如修改辛普森的规则，它假设一个圆柱形左心室形态10来估算。由于心肌梗死后左心室重构不过的结果，心脏尺寸变化。因此，这种特定的几何假设不能进行，减少了这种测量31的准确性和可靠性。 这个问题可以通过使用三维超声心动图以获得完整的左心室的3D图像来解决。在猪心外膜由三维超声心动图LVEF评估显示，与黄金标准CMRI 24,32极好的相关性。然而，这需要之前AMI诱导基线测量手术。不管使用哪种方法， 即，打开胸与subxiphoidal方法，对于心外膜超声微创手术已被证明是心脏保护12,33,34。伴随粘连阻碍resternotomy，这使得外膜echocardiograPHY不可取的基线测量在一个封闭的胸AMI model.To避免这些缺点，心脏的三维图像可以通过3D食管超声心动图（3D-TEE）获得。该技术是可移植的，广泛使用的和允许连续测量和整个左心室体积的可视化。此外，它是可靠的，相对便宜和安全的。 需要注意的是它TEE探头轻轻插入口腔和食道，由于在食管憩室结束了并施加过大的压力可能会导致食道破裂是很重要的。此外，由于胃和心脏的解剖关系从人不同，3D-TEE猪不允许区域测量（ 如 ，应变，组织多普勒成像）和被限制在体积测量。在手稿中提供的数据，观察AMI后没有增加的EDV 7天。需要较长的随访期间，广泛带动adversË重塑，进而增加EDV在几个星期随访11。 与常规的超声心动图，基于导纳光伏环路适度高估左室容积，在基线35和8周随访24的后。不过，还算良好的相关性和高度CMRI协议已被发现。虽然相对于基准PV环测量几个星期后急性心肌梗死是不太准确的，LV尺寸和衍生于此（LVEF）是心脏功能35的全球评估是有用的。 另外，光伏环路提供有关固有心肌性能，如ESPVR特定信息。由于TTE和TEE区域功能测量是有限的，心外膜超声心动图是在基线不可取，PV回路提供内在的心肌功能的评估优雅和安全的技术。无论在ESPVR斜坡下降和典型的SHIFT为V 0可以用于比较不同的治疗剂。这些古典特色，从泛缺血体外心脏犬患进行验证。因此，在局部缺血模型，如急性心肌梗死模型中，这些具体特征不总是存在，这可以归因于许多因素，其中的心室重构和局部缺血是最重要的25,36,37。 充足的数据采集，这是确保转换电导卷时，获取PV循环时无心律失常存在的关键。如果心律失常存在时，重新定位在PV环的导管，因此不会刺激心肌。抗心律失常药物的给药（ 例如，150 - 300毫克胺碘酮）可能也有帮助。但是，请注意几个小时内PV环收购后急性心肌梗死是不可靠的，由于频繁的性心律失常（如室性早搏，bigemini）。&lt;/ P&gt; 略微前进或缩回光伏循环导管插入LV或者从肌肉壁也可能有助于改善光伏环的形状。改变PV回路导管定位后，请务必仔细检查最大充分放置段被选中。 总之，目前介绍于与用于新的治疗剂的评价附加值的先前描述猪心肌梗死模型心脏评估了三种方法来减少正在进行的心脏衰竭流行病的负担。

减少射血分数（HFREF）心脏衰竭占所有心脏衰竭病例的50％，估计影响1 -人的2％，在西方世界1。其最常见的病因是急性心肌梗死（AMI）。由于AMI后急性死亡率，由于认识的提高和改进的治疗方案显著下降，重点已经转向了慢性后遗症;其中最突出的HFREF 2,3。连同增加的医疗费用4，心脏衰竭的日益流行强调需要新颖的诊断和治疗方法，它可以在不利的重构的高度平移猪模型如前所述5进行研究AMI后。 不利的重塑两者，决定因素（ 例如，梗死大小）和功能评估（ 例如 ，超声心动图）经常用于新疗法功效测试，指示相对的需要iable和相对便宜的方法。目前本文的目的是通过引入重要和可靠结果的措施为在急性心肌梗死的猪模型中的功效的测试，以满足这一需要。这些措施包括在风险（AAR），3D食管超声心动图（3D-TEE）和详细的基于准入压量（PV）循环收购涉及面积心肌梗死面积（IS）。 梗塞面积是不利的重塑和生存的AMI后6的主要决定因素。尽管缺血心肌可能挽救可逆损伤的心肌细胞，并限制梗塞尺寸的及时再灌注，灌注本身导致通过氧化应力的产生和不成比例的炎症反应的其他损害（缺血再灌注损伤（IRI））7。因此，IRI已被鉴定为有希望的治疗靶标。新的治疗的减小梗塞尺寸的能力是通过相对于评估梗死大小量化在风险（AAR）的区域。 AAR量化是强制性的，以校正在动物模型中的冠状动脉解剖的个体间变异性，作为较大AAR导致较大的绝对梗塞大小。因为梗塞大小，直接关系到心脏功能和心肌收缩力，在AAR变化可以影响无关研究治疗方式8的结果的措施。 三维食管超声心动图（3D-TEE）是测量心脏功能非侵入性安全，可靠，最重要的是，在临床应用廉价的方法。而经胸超声心动图（TTE）的图像不限于猪9 2D胸骨旁长期和短轴视图，3D-TEE可以用来获得左心室的完整的三维图像。因此，它不需要左心室（LV）卷的数学近似，如修改后的辛普森的第10条。后者达不到科尔的ectly估计左室重构后左室容积由于缺乏圆柱形几何11。此外，3D-TEE超过心外膜超声优选，因为它不要求手术干预，其中已经观察到施加在本模型12的心脏保护作用。虽然对于心肌功能的评估使用2D-TEE的已13,14之前进行了说明，关于心室几何限制是类似于在2D-TTE观察取决于LV重塑的程度。因此，较大的梗塞（因而心脏衰竭的可能性越高），越容易二维测量成为由不正确的几何假设有缺陷和需要3D技术越高。 尽管如此，大多数成像方式在他们的评估心肌的固有功能特性的能力的限制。环光伏提供此类相关的其他信息，因此他们的收购在下面详细描述。

<table><tbody><tr><td>&lt;strong&gt;3-dimensional Transesophageal Echocardiography&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>iE33 ultrasound device</td><td>Philips</td><td>-</td><td></td></tr><tr><td>X7-2t transducer</td><td>Philips</td><td>-</td><td></td></tr><tr><td>Aquasonic&amp;reg; 100 ultrasound transmission gel</td><td>Parker Laboratories Inc.</td><td>01-34</td><td>Alternative product can be used</td></tr><tr><td>Battery handle type C (laryngoscope handle)</td><td>Riester</td><td>12303</td><td></td></tr><tr><td>Ri-Standard Miller blade MIL 4 (laryngoscope blade)</td><td>Riester</td><td>12225</td><td></td></tr><tr><td>Qlab 10.0 (3DQ Advanced) analysis software</td><td>Philips</td><td>-</td><td></td></tr><tr><td>&lt;strong&gt;Name&lt;/strong&gt;</td><td>&lt;strong&gt;Company&lt;/strong&gt;</td><td>&lt;strong&gt;Catalog Number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>&lt;strong&gt;Pressure-volume loop acquisition&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Cardiac defibrillator</td><td>Philips</td><td></td><td></td></tr><tr><td>0.9% Saline</td><td>Braun</td><td></td><td></td></tr><tr><td>8 F Percutaneous Sheath Introducer Set</td><td>Arrow</td><td>CP-08803</td><td>Alternative product can be used</td></tr><tr><td>9 F Radifocus&amp;reg; Introducer II Standard Kit&amp;nbsp;</td><td>Terumo</td><td>RS*A90K10SQ</td><td>Alternative product can be used</td></tr><tr><td>8 F Fogarty catheter</td><td>Edward Life Sciences</td><td>62080814F</td><td>Alternative product can be used</td></tr><tr><td>7 F Criticath&amp;trade; SP5107H TD catheter (Swan-Ganz)</td><td>Becton Dickinson (BD)</td><td>680078</td><td>Alternative product can be used</td></tr><tr><td>Ultraview SL Patient Monitor and Invasive Command Module (external cardiac output device)</td><td>Spacelabs Healthcare</td><td>91387</td><td>Alternative product can be used</td></tr><tr><td>ADVantage system&amp;trade;</td><td>Transonic SciSense</td><td>-</td><td></td></tr><tr><td>7 F Tetra-polar admittance catheter (7.0 VSL Pigtail / no lumen)</td><td>Transonic SciSense</td><td>-</td><td></td></tr><tr><td>Multi-channel acquisition system (Iworx 404)</td><td>Iworx</td><td>-</td><td></td></tr><tr><td>Labscribe V2.0 analysis software</td><td>Iworx</td><td>-</td><td>Alternative product can be used</td></tr><tr><td>&lt;strong&gt;Name&lt;/strong&gt;</td><td>&lt;strong&gt;Company&lt;/strong&gt;</td><td>&lt;strong&gt;Catalog Number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>&lt;strong&gt;Infarct size / area-at-risk quantification&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Diathermy</td><td>-</td><td></td><td>Alternative product can be used</td></tr><tr><td>Lebsch knife</td><td>-</td><td></td><td>Alternative product can be used</td></tr><tr><td>Hammer</td><td>-</td><td></td><td>Alternative product can be used</td></tr><tr><td>Bone marrow wax</td><td>Syneture</td><td></td><td>Alternative product can be used</td></tr><tr><td>Klinkenberg scissors</td><td>-</td><td></td><td>Alternative product can be used</td></tr><tr><td>Retractor</td><td>-</td><td></td><td>Alternative product can be used</td></tr><tr><td>Surgical scissors</td><td>-</td><td></td><td></td></tr><tr><td>7 F Percutaneous Sheath Introducer Set&amp;nbsp;</td><td>Arrow</td><td>CP-08703</td><td>Alternative product can be used</td></tr><tr><td>8 F Percutaneous Sheath Introducer Set&amp;nbsp;</td><td>Arrow</td><td>CP-08803</td><td>Alternative product can be used</td></tr><tr><td>7 F JL4 guiding catheter&amp;nbsp;</td><td>Boston Scientific</td><td>H749 34357-662</td><td>Alternative product can be used</td></tr><tr><td>8 F JL4 guiding catheter&amp;nbsp;</td><td>Boston Scientific</td><td>H749 34358-662&amp;nbsp;</td><td>Alternative product can be used</td></tr><tr><td>COPILOT Bleedback Control Valves&amp;nbsp;</td><td>Abbott Vascular</td><td>1003331</td><td>Alternative product can be used</td></tr><tr><td>BD Connecta&amp;trade;&amp;nbsp;</td><td>Franklin Lakes</td><td>394995</td><td>Alternative product can be used</td></tr><tr><td>Contrast agent</td><td>Telebrix</td><td></td><td></td></tr><tr><td>Persuader 9 Steerable Guidewire 9 (0.014&quot;, 180 cm, straight tip), hydrophilic coating</td><td>Medtronic Inc.</td><td>9PSDR180HS</td><td>Alternative product can be used</td></tr><tr><td>SAPPHIRE&amp;trade; Coronary Dilatation Catheter (PTCA balloon suitable for the size of the particular coronary artery (2.75 - 3.25 mm))</td><td>OrbusNeich</td><td>103-3015</td><td>Alternative product can be used</td></tr><tr><td>Evans Blue&amp;nbsp;</td><td>Sigma-Aldrich</td><td>E2129-100G</td><td>Toxic. Alternative product can be used</td></tr><tr><td>2,3,5-triphenyl-tetrazolium chloride (TTC)</td><td>Sigma-Aldrich</td><td>T8877-100G</td><td>Irritant. Alternative product can be used</td></tr><tr><td>9 V Battery</td><td>-</td><td>-</td><td></td></tr><tr><td>Ruler</td><td>-</td><td>-</td><td></td></tr><tr><td>Photocamera</td><td>Sony</td><td>-</td><td></td></tr><tr><td>ImageJ</td><td>National Institutes of Health</td><td>-</td><td>Alternative product can be used</td></tr></tbody></table>

primary outcome assessment in a pig model of acute myocardial infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

<html> 3D食管超声心动图 3D食管超声心动图（3D-TEE）可用于全球心脏功能的评估。 AMI后，全球心脏功能健康基线值不同。特别是，左心室射血分数（LVEF）从59±4％至37±6％再灌注后的一周（10）（GPJ面包车豪特，2015）后降低。在行程容积（74±11对47±8毫升）的收缩末期容积（51±7 82±13毫升）和下降的增加，也观察到，而舒张末期容积不会这两个时间点之间的不同（125 ±14至129±13毫升）中。代表性的图像后一周心肌梗死（缺血再灌注）都显示在图3中 ，在我们的丰富经验，我们没有遇到相关TEE任何并发症。 T"FO:保together.within页="1"&gt; 基于纳-压力容积环 压力 - 容积（PV）环既可以采用以评估全球心脏功能和特定固有心肌肌肉性能。前者的结果的测量可在图4A中从图表容易地计算，并包括EDV（右下角），ESV（左上角）和射血分数（（EDV - ESV）/ EDV×100％）。在这两方面，ESV和EDV提供左心室几何的重要信息和LVEF是确定左心室泵血功能的重要举措。先前的研究相比，基于纳光伏循环在急性心肌梗死24的猪模型金标准心脏磁共振成像（CMRI）。八周，PV环测量显著高估既ESV和EDV。关于然而，LVEF，PV环和CMRI之间无显著差异。此外，这两种技术niques显示EDV和LVEF的一个相当良好的相关性。 对于心内的性能，不同的测量可以衍生自光伏循环，如收缩末期和舒张末期压力-容积关系（ESPVR; EDP​​VR）25。与预压减少和收缩和舒张功能参数的一些示例代表光伏环路图像示于图4B。该ESPVR斜率减小，表明收缩力下降。可以从光伏环路导出附加有价值功能参数在表1中。 梗死面积/地区在风险量化 在雌性Dalland长白猪（6个月; 60 - 70公斤），左前闭塞降支（LAD）直接远离第一间隔和第一对角支杜环75分钟，导致一个区域在左心室（LV）的22±2％的风险（AAR）（N = 5）（GHJM Ellenbroek，2015）。梗塞大小构成了左心室的16±2％和AAR的73±7％。这相当大的IS / AAR已被选定为作为患者有较大的梗死面积较容易出现心脏衰竭的发展比患者更小的梗死面积。在猪，最大的治疗效果，因此可以应用75分钟缺血时获得的。此外，由于更大的梗塞大小，心脏功能恶化，这允许功能改善以及。当施加索引缺血时间较短，心肌梗死大小是低级和功能仅轻度受损，其允许只的功能改善非常小的窗口图5示出了一个TTC和伊文思蓝染色，它允许清晰的代表性例子3个领域的鉴别:1）远程心肌，2）AAR，以及3）心肌梗死&lt;。/ P&gt; <img alt="图1" src="/files/ftp_upload/54021/54021fig1.jpg" /> 图1.实验方案的时间安排。下面的时间表提供了用于猪心肌梗死模型中最重要的实验步骤的概述。麻醉的适当诱导之前每次测量是必需的。时间指示可以在每个程序下进行观察。 72小时 - 梗死面积是24后的最好评价。 3D-TEE和PV环的数据采集可以在基线和短期和长期随访进行。 AMI后的第一个小时，心律失常频繁，可与心脏血流动力学干扰很大，因此防止可靠的数据采集。 AMI:急性心肌梗死; 3D-TEE:三维食管超声心动图; PV环:压力容量环<a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54021/54021fig1large.jpg" target="_blank">请点击这里查看大versio</a>这个数字的n个。 <img alt="图2" src="/files/ftp_upload/54021/54021fig2.jpg" /> 图2.定位和3D TEE图像的获取，前后位（A）和中侧食管的3D-TEE探头定位的（B）的X射线图像。图像采集如下于左心房，左心室和主动脉（C）以及左侧心房和左心室（D）的垂直影像的正确可视化。 3D-TEE:三维食管超声心动图<a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54021/54021fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图3" src="/files/ftp_upload/54021/54021fig3.jpg" /> 图3.全卷的左心室3D-TEE图像。 </str翁&gt;左心室一周3D-TEE录音急性心肌梗死（75分钟）和再灌注后。垂直的左心房和左心室的长轴图像可以在上半部面板观察（A，B）。左心室的多个横截面图像（D）的的放大例（C）显示在下半部面板。 3D-TEE:三维食管超声心动图<a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54021/54021fig3large.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/54021/54021fig4.jpg" /> 图4.压力容量环的图像在基线和心肌梗死后。呼吸暂停在基线（蓝色）和8周AMI后代表PV环的图像（ 即 ，暂停通风）（红色）（A）。在EDV和ESV和SV的降低增加可以观察到，这表明在LVEF（％）的降低。与预压减少光伏环路图像被用来评估固有心肌功能参数（B）。与基线相比，心肌梗死表示从ESPVR（直蓝色和红色线）衍生于收缩减少。 PV循环:压力容量环; AMI:急性心肌梗死; EDV:舒张末期容积; SV:每搏输出量; LVEF:左室射血分数; ESPVR:收缩末期压力容积关系， <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54021/54021fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图5" src="/files/ftp_upload/54021/54021fig5.jpg" /> 图5.梗死面积和区高危染色，梗死面积和面积高危染色邻形象代表F型急性心肌梗死（75分钟）和随后的再灌注三天后左心室。 （出血性）梗死组织中可以观察到玫瑰色棕色和灰白色的，而边境区染成红色。周围的蓝染区域表示远程心肌。 <a href="https://www-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54021/54021fig5large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td colspan="2"> 体积参数 </td><td colspan="2"> 压力参数 </td><td colspan="2"> 装载无关的参数 </td><td> 其他 </td></tr><tr><td> 收缩压 </td><td> 舒张 </td><td> 收缩压 </td><td> 舒张 </td><td> 收缩压 </td><td> 舒张</td><td> 其他 </td></tr><tr><td> ESV </td><td> EDV </td><td> ESP </td><td> EDP </td><td> ESPVR </td><td> EDP​​VR </td><td> HR </td></tr><tr><td colspan="2"></td><td> DP / DT </td><td> DP / DT </td><td> ËES </td><td> PRSW </td><td> SW </td></tr><tr><td colspan="2"> 衍生工具 </td><td></td><td> τ（tau蛋白） </td><td> ESV100 </td><td></td><td> PRSW </td></tr><tr><td colspan="2"> LVEF，SV，CO </td><td></td><td> PHT </td><td> Ë 一 </td><td></td><td> DP / DV </td></tr></tbody></table> 表1.有价值功能参数，可以从压力-容积环得到。分为体积，压力和负载无关的参数，该表描述了最常用的（收缩压和舒张压）参数从光伏衍生循环。 PV循环:压力容量循环; ESV:收缩末期容积; EDV:舒张末期容积; LVEF:左室射血分数; SV:每搏输出量; CO:心输出量; ESP:收缩末期压力; DP / DT:压力导数; τ（头）:等容舒张常数; PHT:压力一半时间; ESPVR:收缩末期压力容积关系; ËES:收缩末期弹性; ESV100:收缩末期容积压力（100毫米汞柱）纠正; Ë 一个 :动脉弹性; EDP​​VR:舒张末期压力容积关系; PRSW:预紧recruitable行程的工作; HR:心脏率;南方周末:中风工作; DP / DV:EDPVR斜率（室刚度）。

Watch this Scientific Journal Video about Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction at JoVE.com

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

可靠和准确的结果评价是临床前的疗法转化为临床治疗的关键。目前的论文描述了如何评估猪急性心肌梗死模型的心脏功能和损坏3临床相关的主要成果参数。

急性心肌梗死的猪模型主要成果评估

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

primary-outcome-assessment-pig-model-acute-myocardial

Universidad San Sebastian

Research

JoVE Journal

Medicine

11.4K 次观看.  University Medical Center Utrecht. 可靠和准确的结果评价是临床前的疗法转化为临床治疗的关键。目前的论文描述了如何评估猪急性心肌梗死模型的心脏功能和损坏3临床相关的主要成果参数。 

视频: Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Acute Myocardial Infarction in Rats

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial infarction (AMI). This model is also referred to as an acute ischemic cardiomyopathy or ischemia followed by reperfusion (IR); which is induced by an acute 30-minute period of ischemia by ligation of the left anterior descending artery (LAD) followed by reperfusion of the tissue by releasing the LAD ligation (Vasilyev and McConnell). This protocol will focus on assessment of the infarct size and the area-at-risk (AAR) by Evan's blue dye and triphenyl tetrazolium chloride (TTC) following 4-hours of reperfusion; additional comments toward the evaluation of cardiac function and remodeling by modifying the duration of reperfusion, is also presented. Overall, this AMI rat animal model is useful for studying the consequence of a myocardial infarction on cardiac pathophysiological and physiological function.

The rat model of acute myocardial infarction (AMI) is useful to study the consequence of a MI on cardiac pathophysiological and physiological function.

大鼠急性心肌梗死

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular ...

科研

医学

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 ...

Histological Quantification of Chronic Myocardial Infarct in Rats

Myocardial infarction is defined as cardiomyocyte death due to prolonged ischemia; an inflammatory response and scar formation (fibrosis) follow the ischemic injury. Following the initial acute phase, chronic remodeling of the left ventricle (LV) modifies the structure and function of the heart. Permanent coronary ligation in small animals has been widely used as a reference model for a chronic model of MI. Thinning of the infarcted wall progressively develops to transmural fibrosis. Histological assessment of infarct size is commonly performed; nevertheless, a standardization of the methods for quantification is missing. Indeed, important methodological aspects, such as the number of sections analyzed and the sampling and quantification methods, are usually not described and therefore preclude comparison across investigations. Too often, quantification is performed on a single section obtained at the level of the papillary muscles. Because novel strategies aimed at reducing infarct expansion and remodeling are under investigation, there is an important need for the standardization of accurate heart sampling protocols. We describe an accurate method to quantify the infarct size using a systematic sampling of harvested rat heart and image analyses of trichromatic stained histological sections obtained from base to apex. We also provide evidence that calculating the expansion index (EI) allowed for infarct size assessment, taking into account changes of the left ventricle throughout the remodeling.

The post-mortem assessment of myocardial infarction (MI) in rodents is based on quantification of the infarct on stained heart sections. We describe an accurate method to quantify the infarct size using systematic sampling of harvested rat hearts from base to apex and image analyses of trichrome-stained histological sections.

大鼠慢性心肌梗塞的组织学定量分析

Myocardial infarction is defined as cardiomyocyte death due to prolonged ischemia; an inflammatory response and scar formation (fibrosis) follow the ...

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 ...

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 ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

使用左前部降冠动脉的永久结扎的月心肌梗死模型

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major causes of mortality and morbidity around the world. Cell-based therapies for cardiac repair and improvement of left ventricular function after MI have attracted considerable attention. Accordingly, the safety and efficacy of these cell transplantations should be tested in a preclinical large animal model of HF prior to clinical use. Pigs are widely used for cardiovascular disease research due to their similarity to humans in terms of heart size and coronary anatomy. Therefore, we sought to present an effective protocol for the establishment of a porcine chronic HF model using closed-chest coronary balloon occlusion of the left circumflex artery (LCX), followed by rapid ventricular pacing induced with pacemaker implantation. Eight weeks later, the stem cells were administered by intramyocardial injection in the peri-infarct area. Then the infarct size, cell survival, and left ventricular function (including echocardiography, hemodynamic parameters, and electrophysiology) were evaluated. This study helps establish a stable preclinical large animal HF model for stem cell treatment.

We sought to establish a swine model of heart failure induced by left circumflex artery blockage and rapid pacing to test the effect and safety of intramyocardial administration of stem cells for cell-based therapies.

建立干细胞治疗心肌梗塞心力衰竭的猪模型

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.
Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult G&#246;ttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model.
MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in G&#246;ttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in G&#246;ttingen minipigs and at 2 months in Landrace pigs, respectively.
Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in G&#246;ttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, G&#246;ttingen minipigs showed a slight increase in LVED mass only at 6 months.
In summary, this is the first characterization of post-MI HF in G&#246;ttingen minipigs in comparison to Landrace pigs, showing that the G&#246;ttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the G&#246;ttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

The overall goal of the current study is to present the techniques of induction of myocardial infarction (MI) and post-myocardial infarction heart failure (post-MI HF) in closed-chest, adult G&#246;ttingen minipigs and the characterization of post-MI HF model in G&#246;ttingen minipigs as compared to Landrace pigs.

封闭胸冠状动脉闭塞/输液模型中的心肌梗塞后心力衰竭

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

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 ...

Transthoracic Echocardiography to Assess Post-Resuscitation Left Ventricular Dysfunction After Acute Myocardial Infarction and Cardiac Arrest in Pigs

One of the main causes of out-of-hospital cardiac arrest is acute myocardial infarction (AMI). After successful resuscitation from cardiac arrest, approximately 70% of patients die before hospital discharge due to post-resuscitation myocardial and cerebral dysfunction. In experimental models, myocardial dysfunction after cardiac arrest, characterized by an impairment in both left ventricular (LV) systolic and diastolic function, has been described as reversible but very little data are available in cardiac arrest models associated with AMI in pigs. Transthoracic echocardiography is the first-line diagnostic test for the assessment of myocardial dysfunction, structural changes and/or AMI extension. In this pig model of ischemic cardiac arrest, echocardiography was done at baseline and 2-4 and 96 hours after resuscitation. In the acute phase, the examinations are done in anesthetized, mechanically ventilated pigs (weight 39.8 &#177; 0.6 kg) and ECG is recorded continuously. Mono- and bi-dimensional, Doppler and tissue Doppler recordings are acquired. Aortic and left atrium diameter, end-systolic and end-diastolic left ventricular wall thicknesses, end-diastolic and end-systolic diameters and shortening fraction (SF) are measured. Apical 2-, 3-, 4-, and 5-chamber views are acquired, LV volumes and ejection fraction are calculated. Segmental wall motion analysis is done to detect the localization and estimate the extent of myocardial infarction. Pulsed Wave Doppler echocardiography is used to record trans-mitral flow velocities from a 4-apical chamber view and trans-aortic flow from a 5-chamber view to calculate LV cardiac output (CO) and stroke volume (SV). Tissue Doppler Imaging (TDI) of LV lateral and septal mitral anulus is recorded (TDI septal and lateral s&#39;, e&#39;, a&#39; velocities). All the recordings and measurements are done according to the recommendations of the American and European Societies of Echocardiography Guidelines.

Transthoracic echocardiography is the first-line diagnostic test for post-resuscitation left ventricular dysfunction and structural changes in a pig model of cardiac arrest.