Name: shunt surgery, right heart catheterization, and vascular morphometry in a rat model for flow-induced pulmonary arterial hypertension
Uploaded: 2017-02-11T13:00:00.000+00:00
Duration: 9 min 23 s
Description: Watch this Scientific Journal Video about Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension at JoVE.com

This study was supported by the Netherlands Cardiovascular Research Initiative, the Dutch Heart Foundation, the Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences (CVON nr. 2012-08, PHAEDRA, The Sebald fund, Stichting Hartekind).

涉及受试动物的程序已通过荷兰中央委员会的动物实验和动物保健委员会在格罗宁根大学医学中心（NL）。使用了这两个的Wistar和刘易斯大鼠180和300克之间的权。 1.住房和驯化<ol><li>在中央动物设施，房屋大鼠的每笼5组到任后。在7天的适应期后，习惯于老鼠对人类的处理，但不进行任何实验程序。 </li></ol> 2.准备和无菌Monocrotalin注射<ol><li>为1毫升60毫克/毫升monocrotalin（MCT）溶液，称重60毫克monocrotalin的在2毫升管中。添加0.9％的NaCl的700微升。加入1 M盐酸200微升。温热下热运转的自来水和涡流它在管中的溶液。使用6N的氢氧化钠以使pH向7.0。使用无菌技术制备的MCT的用于注入啮齿动物。 </LI&gt; <li>注入无菌60毫克/毫升的MCT每kg皮下颈部溶液（0.3毫升的60毫克/毫升的MCT为一个300-G大鼠）1毫升。注意:我们不喜欢使用更小的体积由于机会较大的注射剂量不恰当的。 </li></ol> 3.主动脉腔静脉分流手术<ol><li>麻醉。 <ol><li>填用5％异氟烷/ 100％O 2的感应腔（流速:1升/分钟），然后将鼠在腔室。通过执行后脚趾捏检查麻醉深度足够。称量老鼠。 </li><li>刮脸和清洁腹部过了约8厘米长，宽3厘米的区域。放置老鼠在其上通过一个无菌垫覆盖的热垫（37℃）背部。 </li><li>放置吻在通气面罩/罩2 - 3％异氟烷/ 100％O 2（流速:1升/分钟）。通过执行后趾压紧检查麻醉深度。应用眼膏，以防止干燥，而在麻醉下。 </li></ol></li><li>分流苏尔格里。 <ol><li>擦洗氯化物hexidine消毒皮肤。注入0.01毫克/千克丁丙诺啡皮下术后镇痛。 </li><li>使用无菌器械进行手术。作出切口在腹部＃10解剖刀刀片上的中线，在开始向下延伸到正好在生殖器上述膈下1厘米。 </li><li>抬起用棉签肠道，盖在无菌，湿纱布（0.9％NaCl）中的肠，并把它们放置在动物的左侧。 </li><li>用棉签到附加腹主动脉和下腔静脉周围组织的膜分离。 注意:不要解剖主动脉和下腔静脉之间的隔膜。 </li><li>使用分裂镊子，去除血管周围主动脉脂肪只是分叉以上，仅在主动脉的右侧，并且只在其中针将被插入的位点。 </li><li>用棉签主动脉和下腔静脉由2毫米分离苏佩rior到针会为了要Biemer钳创造空间被插入的位点。 </li><li>在这个区域中，首先放置一个松散结扎（5-0缝合）围绕主动脉。通过放置一个科赫尔钳在其上创建的结扎张力，然后将科赫尔优于切口（ 图1A）。放置Biemer钳只是优于结扎（FIGURē1A）。 </li><li>用棉签，如向远端尽可能压缩腔静脉阻塞的流动（ 图1A）。弯针（18克在这个协议）成45度角，与朝外面（ 图1A）孔口指点。 </li><li>以90度的角度，插入针在主动脉，只是分叉上方，与针指向的孔向左侧（ 图1A）。操纵针向左的前端，将其插入腔静脉。 注:针尖现在应该VISI竹叶提取在腔静脉（ 图1B）。 </li><li>使用第二棉签推剩余的血液在主动脉出插入位点的，以防止血栓形成。干周围用无菌纱布分流的区域，以便使胶充分粘。 </li><li>拉动整个针从主动脉并立即应用组织胶一滴到在主动脉穿刺部位。确保不要棉签粘上来组织。松开主动脉。 </li><li>拉动和释放的主动脉近端分流结扎手动验证分流。松动应上色腔静脉远端鲜红色分流和分流站点上创建的动荡。 注:紧缩将会把血液中的腔静脉回暗红色。 </li><li>放置肠放回动物。关闭肌肉层和皮肤可吸收缝线4-0。通风用100％O 2的动物从麻醉中恢复。 注意:不要让一个ANI发作无人值守，直到它已经恢复了足够的意识，以保持胸骨斜卧。 </li></ol></li><li>假手术。 <ol><li>执行上述所有的方法，只是在插入针的进入主动脉。 </li></ol></li><li>手术后的护理。 <ol><li>放置老鼠在单个笼和入在37℃的培养箱，直到第二天早上。 </li><li>周围手术后6小时，注入0.01毫克/千克丁丙诺啡皮下术后镇痛。如果老鼠显示不适的迹象，第二天早上重复。 注意:手术后第3天，老鼠喜欢吃少喝（当饲料及饮水与药物混合，这一点尤为重要）。大多数老鼠显示手术后第3天的正常行为。如果没有，密切监测。 1周后超过15％的重量损失被认为是不正常的，并且这样的大鼠应在循环血液量而麻醉下的提取安乐死。 </li></ol></li></ol>注意:在这个协议中，该动物是由循环血液量而麻醉下的提取安乐死。 <ol><li>手术（MF8）对早期细胞和功能性反应肺血流增加（ 例如，基因上调或早期转录因子）后牺牲1天。 </li><li>手术（MF14）为早期PAH血管表型（膜肥厚内膜无损伤）后牺牲1周。 </li><li>手术（MF21）对于晚期PAH血管表型（标记膜肥厚和内膜增生）与RVP和肺动脉压轻度升高后牺牲2周。 </li><li>手术（MF28）为终末期PAH血管型（标内膜闭塞）和强大的海拔RVP和肺动脉压后牺牲3周。右心衰竭的临床症状在这个阶段很常见。 </li><li>第28天（MF-RVF后牺牲）对PAH相关的右心室衰竭（RVF），临床上定义为呼吸困难，严重嗜睡，体重下降（&lt;1周10％）。终止时，老鼠的这些迹象之一是存在。通常情况下，老鼠患天28和35之间，这些症状，如果无人看管，在该时间间隔期间死亡油然而生。 </li></ol> 5.右心导管<ol><li>麻醉。 <ol><li>填用5％异氟烷/ 100％O 2的感应腔（流速:1升/分钟），然后将鼠在框中。通过执行后脚趾捏检查麻醉深度足够。称量老鼠。 </li><li>剃和在大鼠的右腹侧清洁颈部和，对于心动协议，胸部和上腹部。 </li><li>放置在其上的热垫（37℃）背面的大鼠和放置鼻子在通气面罩/罩2 - 3％异氟烷/ 100％O 2（流速:1升/分钟）。吻应该面对朝研究员。 </li><li&gt;检查麻醉深度。小心大鼠重症PH。如果心脏速率降低，减少麻醉深度。优选的，执行20分钟之内的所有的测量。应用眼膏，以防止干燥，而在麻醉下。 </li></ol></li><li>超声心动图的协议。 <ol><li>根据由布里泰恩等人描述的协议来执行超声心动图。在朱庇特13。 </li></ol></li><li>导尿协议。 注意:此协议使用一个预成形端部的刚性套管弯曲20度，以指导15厘米硅导管 ，从尖端球2毫米。与其孔口微曲到内部的20-G 针用于插入套管插入右颈静脉（见材料的列表）。在PAH进展和控制的任何阶段只可在该协议中使用。 <ol><li>用消毒氯hexidine颈部。做一个1.5厘米的切口，在右腹侧＃10手术刀刀片颈部，从右侧锁骨到下颌骨。 </li><li>用剪刀传播组织。使用镊子，轻轻直到出现颈静脉拉开组织。周围解剖颈膜使用静脉分裂镊子。 </li><li>通过放置一个松散的结扎（缝合5-0）船舶周围戴上颈静脉的张力。加剧紧张局势，并用胶带将结扎到通气面罩（ 图 2A）。 </li><li>下游的插入位点，放置一个松散结扎血管周围收紧后套管是在原地 ，以防止泄漏和压力损失。 </li><li>使用镊子的把手，稍微弯曲的孔的内部的20-G针的前端与导管进行插管。 </li><li>引入20-G针插入静脉的尖端，并迅速放入含有容器内的导管插管。拔出针头，然后关闭结扎已在步骤5.3.4准备。 </li><li>进行含有导管插入颈静脉插管。套管的前端是在20度曲线（见步骤5.3.5）。操纵锁骨下套管和前进少许进入右心房（ 图2C）。 </li><li>进入右心室，指向套管向左的前端，朝向心脏（ 图2D）。在床旁监护仪，一个RV压力曲线应该出现，匹配图2D。 </li><li>当RV压力曲线是恒定的，写下收缩和舒张右心室压力1（sRVP1 / dRVP1）。 </li><li>操纵套管的左侧和向上的尖端。套管（ 图2E）内推进导管。 </li><li>推进导管进入主肺动脉（PA）。经过肺动脉瓣时，应感到无阻力。 注:当导管进入主肺动脉，则Diastolic压力将上升。在床边监护仪，一个PA压力曲线应该出现，配套图2E。 </li><li>当PA压力曲线是恒定的，记下收缩压，舒张压，平均PA的压力1（sPAP1，dPAP1，mPAP1）。 </li><li>进一步推进套管内的导管，直到导管的前端的球在肺动脉被楔入。观察床旁监护仪下降压力曲线和匹配图2F楔形压力曲线。 </li><li>当楔压曲线是恒定的，记下收缩压，舒张压，平均楔压。 </li><li>拉回导管慢慢地，随后测量并记下sPAP2，dPAP2，mPAP2，sRVP2和dRVP2值，床旁监护仪上显示。 </li><li>当房车，略有回拉套管和导管测量平均右房压（RAP）。曲线应该与图2A的RAP曲线。 没有TE:在这个协议中，将大鼠的导尿协议之后，由循环血液量的同时麻醉下提取安乐死。 </li></ol></li></ol> 6.形态学评估和形态测量注意:在这个协议中，该动物是由循环血液量而麻醉下的提取安乐死。在PAH进展和控制的任何阶段只可在该协议中使用。 <ol><li>处死后，通过切割约5mm支气管分叉以上和肺连接到心脏血管气管取出肺。把肺部冷盐水。解剖左肺。切在分叉的左主支气管。 </li><li>填写一个50毫升的注射器，用4％多聚甲醛，附加一个管套管注射器，并悬挂约工作台上方一米的注射器。适合在左主支气管插管被动填充用多聚甲醛的肺。手柄谨慎多聚甲醛。 </li><li>孵育在多聚甲醛左肺48小时。 </li><li>通过在70％乙醇（1小时），80％乙醇（1小时），90％乙醇（1小时），100％乙醇（3小时），混合二甲苯（2小时），和石蜡连续孵育它脱水左肺（ 2小时）。 </li><li>嵌入左肺石蜡，面向磁带肺肺门。 </li><li>染色用维尔赫夫或弹性van Gieson染色染色的石蜡包埋，4微米肺切片，按照制造商的说明29。确保弹性薄片是公分化（ 如图3）。扫描染色切片放大40倍。 </li><li>划分成肺4个象限。在每一个象限中，找到10容器的外径&lt;50微米（帧内腺泡）和10容器的外径&gt; 50微米（预腺泡）。拍照（每肺2×40图片）。放大随机高达20倍的放大倍率和照片每艘船在视这一领域，以尽量减少选择偏差。 </li><li>排除具有&gt; 2最长/最短径比，一个不完整的圆形，或血管壁的四分之一以上的崩溃血管。 注:排除的容器的一个例子显示于图3b中制作的相同的放大倍率（40X）每一画面，并包括一个比例尺。 </li><li>打开ImageJ的与第一张照片。绘制比例尺的直线上的图象通过" 分析 "，设置刻度 和"设置规模 。" 素以" 距离"，使用图片的比例尺上的值。用微米（μm），为长度单位。将比例设置为全局。 </li><li>使用" 写意选择 ，" 画一条线上的管腔面积（ 图3）的内边界， 并使用"测量 " （CRTL M）来衡量这个区域。然后，周围画外ELAST线集成电路层（ 图3）来测量总血管面积。 </li><li>计算管腔和外径（ <img alt="方程" src="/files/ftp_upload/55065/55065eq1.jpg" /> ）使用<img alt="方程" src="/files/ftp_upload/55065/55065eq2.jpg" /> 。 </li><li>使用计算壁厚<img alt="方程" src="/files/ftp_upload/55065/55065eq3.jpg" /> 。 </li><li>通过计算墙/管腔比<img alt="方程" src="/files/ftp_upload/55065/55065eq4.jpg" /> 。 </li><li>使用计算遮挡比分<img alt="方程" src="/files/ftp_upload/55065/55065eq5.jpg" /> 。 </li><li>得分上肌在容器（无，部分，或总肌）（ 图3B）。 注:船只具有双重弹性薄片的一半以上的圆周被定义为完全肌型。具有双弹性薄片不到一半的圆周血管被定义为部分肌型。 </li><li>得分上neoi的存在下容器ntima（是或否）（ 图3C）。 注:船舶没有明确定义的内弹力层与（通常偏心）管腔闭塞合并被定义为内膜病变。 </li></ol>

<ol>
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G., Bartelds, B., Molema, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Egr-1+expression+during+neointimal+development+in+flow-associated+pulmonary+hypertension.">Egr-1 expression during neointimal development in flow-associated pulmonary hypertension.</a> Am J Pathol. 179 (5), 2199-2209 (2011).</li><li>Borgdorff, M. A., Bartelds, B., Dickinson, M. G., Steendijk, P., de Vroomen, M., Berger, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+loading+conditions+reveal+various+patterns+of+right+ventricular+adaptation.">Distinct loading conditions reveal various patterns of right ventricular adaptation.</a> Am J Physiol Heart Circ Physiol. 305 (3), H354-H364 (2013).</li><li>Ruiter, G., de Man, F. S., Schalij, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversibility+of+the+monocrotaline+pulmonary+hypertension+rat+model.">Reversibility of the monocrotaline pulmonary hypertension rat model.</a> Eur Respir J. 42 (2), 553-556 (2013).</li><li>van Albada, M. E., Bartelds, B., Wijnberg, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+expression+profile+in+flow-associated+pulmonary+arterial+hypertension+with+neointimal+lesions.">Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions.</a> Am J Physiol Lung Cell Mol Physiol. 298 (4), L483-L491 (2010).</li><li>Dickinson, M. G., Kowalski, P. S., Bartelds, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+critical+role+for+egr-1+during+vascular+remodelling+in+pulmonary+arterial+hypertension.">A critical role for egr-1 during vascular remodelling in pulmonary arterial hypertension.</a> Cardiovasc Res. 103 (4), 573-584 (2014).</li><li>van der Feen, D. E., Dickinson, M. G., Bartelds, M. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Egr-1+identifies+neointimal+remodeling+and+relates+to+progression+in+human+pulmonary+arterial+hypertension.">Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension.</a> Jheart lung transplant. 35 (4), 481-490 (2016).</li><li>Rungatscher, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+overcirculation-induced+pulmonary+arterial+hypertension+in+aorto-caval+shunt.">Chronic overcirculation-induced pulmonary arterial hypertension in aorto-caval shunt.</a> Microvasc Res. 94, 73-79 (2014).</li><li>O'Blenes, S. B., Fischer, S., McIntyre, B., Keshavjee, S., Rabinovitch, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+unloading+leads+to+regression+of+pulmonary+vascular+disease+in+rats.">Hemodynamic unloading leads to regression of pulmonary vascular disease in rats.</a> J Thorac Cardiovasc Surg. 121 (2), 279-289 (2001).</li><li>Sakao, S., Taraseviciene-Stewart, L., Lee, J. D., Wood, K., Cool, C. D., Voelkel, N. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Initial+apoptosis+is+followed+by+increased+proliferation+of+apoptosis-resistant+endothelial+cells.">Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells.</a> FASEB J. 19 (9), 1178-1180 (2005).</li><li>Spiekerkoetter, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=FK506+activates+BMPR2,+rescues+endothelial+dysfunction,+and+reverses+pulmonary+hypertension.">FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension.</a> J Clin Invest. 123 (8), 3600-3613 (2013).</li><li>Nickel, N. P., Spiekerkoetter, E., Gu, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elafin+reverses+pulmonary+hypertension+via+caveolin-1-dependent+bone+morphogenetic+protein+signaling.">Elafin reverses pulmonary hypertension via caveolin-1-dependent bone morphogenetic protein signaling.</a> Am J Respir Crit Care Med. 191 (11), 1273-1286 (2015).</li><li>Meloche, J., Potus, F., Vaillancourt, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bromodomain-containing+protein+4:+The+epigenetic+origin+of+pulmonary+arterial+hypertension.">Bromodomain-containing protein 4: The epigenetic origin of pulmonary arterial hypertension.</a> Circ Res. 117 (6), 525-535 (2015).</li><li>Happ&#233;, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pneumonectomy+combined+with+SU5416+induces+severe+pulmonary+hypertension+in+rats.">Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.</a> Am J Physiol Lung Cell Mol Physiol. 310 (11), L1088-L1097 (2016).</li><li>Ranchoux, B., Antigny, F., Rucker-Martin, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endothelial-to-mesenchymal+transition+in+pulmonary+hypertension.">Endothelial-to-mesenchymal transition in pulmonary hypertension.</a> Circulation. 131 (11), 1006-1018 (2015).</li><li>de Raaf, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=SuHx+rat+model:+Partly+reversible+pulmonary+hypertension+and+progressive+intima+obstruction.">SuHx rat model: Partly reversible pulmonary hypertension and progressive intima obstruction.</a> Eur Respy J. 44 (1), 160-168 (2014).</li></ol>

The authors have nothing to disclose.

该方法描述了一种主动脉腔静脉分流的大鼠MCT创建流动引起的肺动脉高压和技术来评估原则血液动力学和表征的PAH和该模型的组织病理学终点预处理的外科手术。 该议定书和故障排除中关键步骤手术和手术后。在主动脉 - 静脉分流手术，最关键的步骤是主动脉和腔静脉的剥离。括住主动脉和腔静脉应足够解剖膜创造1）的主动脉区域，其中，所述针将被插入...

该方法的目标是创造在大鼠为严重，流动引起的肺动脉高压可再现模型，并测量它的原理的血液动力学和组织病理学终点。 肺动脉高压（PAH）是一种临床综合征，它包括肺血管阻力逐步增加，导致右心室衰竭而死亡。内肺动脉高血压疾病（PH）的上级疾病谱，多环芳烃是最严重的形式，另一种仍然没有治愈1。在PAH的根本动脉的特点是血管重塑的一种典型形式，闭塞血管腔。正常的非肌型容器和内侧容器层的肥大的肌被视为在PAH早期疾病的现象，也见于其他形式的PH 2，并且被认为是可逆3。作为一个PAHdvances，内膜层开始改造，最终形成特征性病变内膜2。内膜型肺血管重构是独家PAH，目前认为是不可逆的4。 由于PAH是一种罕见的疾病，在推进其病理学的理解和新疗法的发展严重依赖动物模型。大鼠monocrotalin（MCT）模型是一个简单的单击模式，已经，并且现在仍然是经常使用的。 MCT是导致伤到肺小动脉和地区炎症5毒素。 60毫克/千克的MCT导致增加的平均肺动脉压（mPAP），肺血管阻力（PVR），以及3后右心室肥大（RVH） - 4周5。该组织形态学无内膜病变5的特点是隔离膜肥厚。该MCT从而大鼠模型表示的PH适度的形式，而不是PAH，虽然它通常呈现为后者。 在与先天性左向右分流（PAH-CHD）相关的PAH的孩子，肺血流增加被认为是内膜病变的7，8，9发展的重要触发。在大鼠中，肺血流增加可由创作腹主动脉和腔静脉，在1990年10首先描述的技术之间的分流来诱导。替代创造增加肺血流量是单侧肺或锁骨下肺动脉吻合术11。这些模型的概念缺点包括由肺，或由于肺血管的医源性损伤致残留肺和自适应通路激活潜在补涨肺动脉吻合术，既混淆增加肺血流量的影响。 当创建主动脉腔静脉分流和肺血流增加是诱发作为第二砸在MCT处理的大鼠，发生特点内膜病变，和多环芳烃是一种严重的和相关的右心室衰竭（RVF）制定3周上升后流程12。 PAH的此模型中的血液动力学级数可以在体内通过超声心动图和右心脏导管插入术进行评估。血管组织形态学，血管壁的厚度，小动脉闭塞程度和参数右心室衰竭形成PAH的体外表征的支柱。 这种方法描述了主动脉腔静脉分流术（AC-分流）详细的手术方案，对心脏导管检查和血管组织形态学定性和定量评估。

<table><tbody><tr><td colspan="4">&lt;strong&gt;Shunt Surgery&lt;/strong&gt;</td></tr><tr><td>Sterile surgical gloves</td><td></td><td></td><td></td></tr><tr><td>Duratears Eye ointment</td><td>Alcon</td><td>10380</td><td></td></tr><tr><td>Chloride-Hexidine</td><td></td><td></td><td></td></tr><tr><td>Cotton swabs</td><td></td><td></td><td></td></tr><tr><td>Histoacryllic tissue glue</td><td>B. Braun Medical</td><td>1050052</td><td></td></tr><tr><td>Silkam 5-0 sutures black non-resorbable</td><td>B. Braun Medical</td><td>F1134027</td><td></td></tr><tr><td>Safil 4-0 sutures violet resorbable</td><td>B. Braun Medical</td><td></td><td></td></tr><tr><td>18 G needle</td><td>Luer</td><td>NN1838R BD</td><td>tip bent in 45 degrees orifice to the outside</td></tr><tr><td>Gauzes 10 x 10 cm</td><td>Paul Hartmann</td><td>407825</td><td></td></tr><tr><td>Temgesic Buprenorphine</td><td>RB Pharmaceuticals</td><td>5429</td><td>subcutaneous injection</td></tr><tr><td>Sodium Chloride 0.9%</td><td></td><td></td><td></td></tr><tr><td>Ventilation mask Rat</td><td></td><td></td><td></td></tr><tr><td>Scalple blade</td><td></td><td></td><td></td></tr><tr><td>Biemer clamp 18 mm, 5 mm opening&amp;nbsp;</td><td>&lt;a href=&quot;https://www.google.nl/url?sa=i&amp;amp;rct=j&amp;amp;q=&amp;amp;esrc=s&amp;amp;source=images&amp;amp;cd=&amp;amp;cad=rja&amp;amp;uact=8&amp;amp;ved=0ahUKEwitqICpkITNAhWiL8AKHe6iCC8QjhwIBQ&amp;amp;url=http%3A%2F%2Fwww.agnthos.se%2Fquote%2Fquote%2Fcaturl%2Fid%2F242%2FBiemer&amp;amp;psig=AFQjCNEnfRXuMQ6Doi4_-2KMYu3qeRovMA&amp;amp;ust=1464777707579746&quot;&gt;AgnTho&lt;/a&gt;</td><td>64-562</td><td></td></tr><tr><td>Heat mat</td><td></td><td></td><td></td></tr><tr><td>Kocher Clamp</td><td></td><td></td><td></td></tr><tr><td>Shaving machine</td><td></td><td></td><td></td></tr><tr><td>Microscope</td><td>Leica</td><td></td><td></td></tr><tr><td colspan="4">&lt;strong&gt;Right Heart Catheterization&lt;/strong&gt;</td></tr><tr><td>Sterile surgical gloves</td><td></td><td></td><td></td></tr><tr><td>Eye ointment</td><td>Duratears</td><td></td><td></td></tr><tr><td>Chloride-Hexidine</td><td></td><td></td><td></td></tr><tr><td>Cotton swabs</td><td></td><td></td><td></td></tr><tr><td>Gauzes 10 x 10 cm</td><td>Paul Hartmann</td><td>407825</td><td></td></tr><tr><td>Silkam 5-0 sutures black non-resorbable</td><td>B. Braun Medical</td><td>F1134027</td><td></td></tr><tr><td>Needle 20 G</td><td>Luer</td><td></td><td>Tip slightly bent to the inside</td></tr><tr><td>Cannula 20 G</td><td>Luer</td><td></td><td>to introduce catheter, tip pre-formed in 20 degrees</td></tr><tr><td>Silastic Catheter 15 cm long</td><td></td><td></td><td>0.5 mm ball 2 mm from tip</td></tr><tr><td>Pressure transducer</td><td>Ailtech</td><td></td><td></td></tr><tr><td>Bedside monitor Cardiocap/5</td><td>Datex-Ohmeda</td><td></td><td></td></tr><tr><td>Shaving machine</td><td></td><td></td><td></td></tr><tr><td>10 mL Syringe</td><td></td><td></td><td></td></tr><tr><td>Sodium Chloride 0.9%</td><td></td><td></td><td>for flushing</td></tr><tr><td colspan="4">&lt;strong&gt;Vascular Morphology&lt;/strong&gt;</td></tr><tr><td>50 mL Syringe</td><td></td><td></td><td></td></tr><tr><td>4% Formaldehyde</td><td></td><td></td><td></td></tr><tr><td>18 G cannula with tube</td><td></td><td></td><td></td></tr><tr><td>Verhoef staining kit</td><td>Sigma-Aldrich</td><td>&lt;a href=&quot;http://www.sigmaaldrich.com/catalog/product/sigma/ht254?lang=en&amp;amp;region=NL&quot;&gt;HT254&lt;/a&gt;</td><td>http://www.sigmaaldrich.com/catalog/product/sigma/ht254?lang=en&amp;amp;region=US</td></tr><tr><td>Digital slide scanner</td><td>Hamamatsu</td><td>C9600</td><td></td></tr><tr><td>ImageJ</td><td></td><td></td><td></td></tr><tr><td>Elastic (Connective Tissue Stain)&amp;nbsp;</td><td>Abcam</td><td>ab150667</td><td>http://www.abcam.com/elastic-connective-tissue-stain-ab150667.html&lt;br /&gt;
http://www.abcam.com/ps/products/150/ab150667/documents/ab150667-Elastic%20Stain%20Kit%20(website).pdf</td></tr></tbody></table>

shunt surgery, right heart catheterization, and vascular morphometry in a rat model for flow-induced pulmonary arterial hypertension

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The shunt is created by inserting an 18-G needle from the abdominal aorta into the adjacent caval vein. Increased pulmonary flow has been demonstrated as an essential trigger for a severe form of PAH with distinct phases of disease progression, characterized by early medial hypertrophy followed by neointimal lesions and the progressive occlusion of the small pulmonary vessels. To measure the right heart and pulmonary hemodynamics in this model, right heart catheterization is performed by inserting a rigid cannula containing a flexible ball-tip catheter via the right jugular vein into the right ventricle. The catheter is then advanced into the main and the more distal pulmonary arteries. The histopathology of the pulmonary vasculature is assessed qualitatively, by scoring the pre- and intra-acinar vessels on the degree of muscularization and the presence of a neointima, and quantitatively, by measuring the wall thickness, the wall-lumen ratios, and the occlusion score.

代表性的结果示于图4中。所提出的研究结果表明MCT +流Lewis大鼠在以下群体的特征:（N = 3），MF8（N = 5），MF14（N = 5），MF28（N = 5）和MF-RVF控制（ N = 10）。统计分析采用与Bonferroni校正方差分析单向进行的。 60毫克/千克的MCT和肺血流增加导致收缩期右心室压的平均上升（sRVP）（23±6到56±11毫米汞柱），肺动脉收缩?...

Watch this Scientific Journal Video about Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension at JoVE.com

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

分流手术，右心导管，血管形态计量学在大鼠模型中的流量引起的肺动脉高压

In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt ...

shunt-surgery-right-heart-catheterization-vascular-morphometry-rat

Research

JoVE Journal

Medicine

16.7K 次观看.  University Medical Center Groningen, University of Groningen. This protocol describes a surgical procedure to create a model for flow-induced pulmonary arterial hypertension (PAH) in rats and the procedures to analyze the principle hemodynamic and histological end-points in this model.

视频: Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

Echocardiographic Assessment of the Right Heart in Mice

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking.
In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.

This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice. Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

右心小鼠的超声心动图评价

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential ...

科研

医学

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular failure. Current treatments are limited. Physiologically, pulsatile blood flow is detrimental to the vasculature. In response to sustained pulsatile stress, vessels release nitric oxide (NO) to induce vasodilation for self-protection. Based on this observation, this study developed a protocol to assess whether an artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia for 3 weeks and compared to a control group of piglets. Once a week, the piglets underwent echocardiography to assess PAH severity. At the end of hypoxia exposure, the piglets were subjected to a pulsatile protocol using a pulsatile catheter. After being anesthetized and prepared for surgery, the jugular vein of the piglet was isolated and the catheter was introduced through the right atrium, the right ventricle and the pulmonary artery, under radioscopic control. Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1) and 30 min after (T2) the pulsatile protocol. It was demonstrated that this pulsatile protocol is a safe and efficient method of inducing a significant reduction in mean PAP via an NO-dependent mechanism. These data open up new avenues for the clinical management of PAH.

Pulmonary hypertension is associated with a significant reduction in pulmonary artery pulsatility, contractility and elasticity, contributing to an increase in pulmonary artery pressure and pulmonary resistance. Using a hypoxic piglet model, this study demonstrated that improving pulmonary artery plasticity using a newly developed pulsatile catheter improves hypoxic pulmonary hypertension.

增加肺动脉脉动流改善缺氧性肺动脉高压的仔猪

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular ...

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. 
Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed.

Pulmonary arterial hypertension (PAH) is a disease of pulmonary arterioles that leads to their obliteration and the development of right ventricular failure. Rodent models of PAH are critical in understanding the pathophysiology of PAH. Here we demonstrate hemodynamic characterization, with right heart catheterization and echocardiography, in the mouse and rat.

肺动脉高压的啮齿动物模型的血流动力学特性

Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle ...

Induction and Phenotyping of Acute Right Heart Failure in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The morphological and functional phenotyping of the right ventricle is of particular importance in the context of hemodynamic compromise in patients with ARHF. Here, we describe a method to induce ARHF in a previously described large animal model of chronic PH, and to phenotype, dynamically, right ventricular function using the gold standard method (i.e., pressure-volume PV loops) and with a non-invasive clinically available method (i.e., echocardiography). Chronic PH is first induced in pigs by left pulmonary artery ligation and right lower lobe embolism with biological glue once a week for 5 weeks. After 16 weeks, ARHF is induced by successive volume loading using saline followed by iterative pulmonary embolism until the ratio of the systolic pulmonary pressure over systemic pressure reaches 0.9 or until the systolic systemic pressure decreases below 90 mmHg. Hemodynamics are restored with dobutamine infusion (from 2.5 &#181;g/kg/min to 7.5 &#181;g/kg/min). PV-loops and echocardiography are performed during each condition. Each condition requires around 40 minutes for induction, hemodynamic stabilization and data acquisition. Out of 9 animals, 2 died immediately after pulmonary embolism and 7 completed the protocol, which illustrates the learning curve of the model. The model induced a 3-fold increase in mean pulmonary artery pressure. The PV-loop analysis showed that ventriculo-arterial coupling was preserved after volume loading, decreased after acute pulmonary embolism and was restored with dobutamine. Echocardiographic acquisitions allowed to quantify right ventricular parameters of morphology and function with good quality. We identified right ventricular ischemic lesions in the model. The model can be used to compare different treatments or to validate non-invasive parameters of right ventricular morphology and function in the context of ARHF.

We present a protocol to induce and phenotype an acute right heart failure in a large animal model with chronic pulmonary hypertension. This model can be used to test therapeutic interventions, to develop right heart metrics&#160;or to improve the understanding of acute right heart failure pathophysiology.

慢性血栓栓塞性肺动脉高压大型动物模型中急性右心衰竭的诱导和表型分析

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The ...

Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of group 2 PH, due to mitral stenosis (MS), to facilitate the investigation of disease mechanisms and potential therapeutic strategies. We present a novel rat model of pulmonary venous congestion-induced pulmonary venous arterialization and group 2 PH caused by left atrial stenosis (LAS). LAS is achieved by constricting the left atrium using a half-closed titanium clip. After the LAS surgery, a rat model with a transmitral inflow velocity greater than or equal to 2.0 m/s on echocardiography gradually develops pulmonary venous arterialization and group 2 PH over an 8- to 10-week period. In this protocol, we provide the step-by-step procedure of how to perform the LAS surgery. The presented LAS rat model mimics MS in humans and is useful for studying the underlying molecular mechanism of pulmonary venous arterialization and for the preclinical evaluation of therapies for group 2 PH.

Left atrial stenosis (LAS) is a novel surgical technique used for studying group 2 pulmonary hypertension (PH) and mechanisms underlying pulmonary venous arterialization. Here, we present a protocol to constrict the left atrium using a titanium clip to cause pulmonary venous arterialization and moderate PH in a rat.

左心房狭窄致大鼠肺静脉动脉化及第2组肺动脉高压

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of ...

The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats

In this protocol, we detail the correct procedural steps and necessary precautions to successfully perform a left pneumonectomy and induce PAH in rats with the additional administration of monocrotaline (MCT) or SU5416 (Sugen). We also compare these two models to other PAH models commonly used in research. In the last few years, the focus of animal PAH models has moved towards studying the mechanism of angioproliferation of plexiform lesions, in which the role of increased pulmonary blood flow is considered as an important trigger in the development of severe pulmonary vascular remodeling. One of the most promising rodent models of increased pulmonary flow is the unilateral left pneumonectomy combined with a "second hit" of MCT or Sugen. The removal of the left lung leads to increased and turbulent pulmonary blood flow and vascular remodeling. Currently, there is no detailed procedure of the pneumonectomy surgery in rats. This article details a step-by-step protocol of the pneumonectomy surgical procedure and post-operative care in male Sprague-Dawley rats. Briefly, the animal is anesthetized and the chest is opened. Once the left pulmonary artery, pulmonary vein, and bronchus are visualized, they are ligated and the left lung is removed. The chest then closed and the animal recovered. Blood is forced to circulate only on the right lung. This increased vascular pressure leads to a progressive remodeling and occlusion of small pulmonary arteries. The second hit of MCT or Sugen is used one week post-surgery to induce endothelial dysfunction. The combination of increased blood flow in the lung and endothelial dysfunction produces severe PAH. The primary limitation of this procedure is that it requires general surgical skills.

The rodent left pneumonectomy is a valuable technique in pulmonary hypertension research. Here, we present a protocol to describe the rat pneumonectomy procedure and postoperative care to ensure minimal morbidity and mortality.

左肺切除术联合单氯联氨酸或苏根为大鼠肺动脉高压的模型

In this protocol, we detail the correct procedural steps and necessary precautions to successfully perform a left pneumonectomy and induce PAH in rats ...

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

小鼠右心室系统及缺氧诱发肺动脉高血压的侵入性血液动力学评估

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. ...

A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats

Pulmonary hypertension due to left heart disease (PH-LHD) is the most common form of PH, yet its pathophysiology is poorly characterized than pulmonary arterial hypertension (PAH). As a result, approved therapeutic interventions for the treatment or prevention of PH-LHD are missing. Medications used to treat PH in PAH patients are not recommended for treatment of PH-LHD, as reduced pulmonary vascular resistance (PVR) and increased pulmonary blood flow in the presence of increased left-sided filling pressures may cause left heart decompensation and pulmonary edema. New strategies need to be developed to reverse PH in LHD patients. In contrast to PAH, PH-LHD develops due to increased mechanical load caused by congestion of blood into the lung circulation during left heart failure. Clinically, mechanical unloading of the left ventricle (LV) by aortic valve replacement in aortic stenosis patients or by implantation of LV assist devices in end-stage heart failure patients normalizes not only pulmonary arterial and right ventricular (RV) pressures but also PVR, thus providing indirect evidence for reverse remodeling in the pulmonary vasculature. Using an established rat model of PH-LHD due to left heart failure triggered by pressure overload with subsequent development of PH, a model is developed to study the molecular and cellular mechanisms of this physiological reverse remodeling process. Specifically, an aortic debanding surgery was performed, which resulted in reverse remodeling of the LV myocardium and its unloading. In parallel, complete normalization of RV systolic pressure and significant but incomplete reversal of RV hypertrophy was detectable. This model may present a valuable tool to study the mechanisms of physiological reverse remodeling in the pulmonary circulation and the RV, aiming to develop therapeutic strategies for treating PH-LHD and other forms of PH.

The present protocol describes a surgical procedure to remove ascending-aortic banding in a rat model of pulmonary hypertension due to left heart disease. This technique studies endogenous mechanisms of reverse remodeling in the pulmonary circulation and the right heart, thus informing strategies to reverse pulmonary hypertension and/or right ventricular dysfunction.

大鼠主动脉切除术治疗左心病肺动脉高压反向血管重塑模型

Pulmonary hypertension due to left heart disease (PH-LHD) is the most common form of PH, yet its pathophysiology is poorly characterized than pulmonary ...

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

The mechanism of right ventricular failure (RVF) requires clarification due to the uniqueness, high morbidity, high mortality, and refractory nature of RVF. Previous rat models imitating RVF progression have been described. Compared with rats, mice are more accessible, economical, and widely used in animal experiments. We developed a pulmonary artery constriction (PAC) approach which is comprised of banding the pulmonary trunk in mice to induce right ventricular (RV) hypertrophy. A special surgical latch needle was designed that allows for easier separation of the aorta and the pulmonary trunk. In our experiments, the use of this fabricated latch needle reduced the risk of arteriorrhexis and improved the surgical success rate to 90%. We used different padding needle diameters to precisely create quantitative constriction, which can induce different degrees of RV hypertrophy. We quantified the degree of constriction by evaluating the blood flow velocity of the PA, which was measured by noninvasive transthoracic echocardiography. RV function was precisely evaluated by right heart catheterization at 8 weeks after surgery. The surgical instruments made inhouse were composed of common materials using a simple process that is easy to master. Therefore, the PAC approach described here is easy to imitate using instruments made in the lab and can be widely used in other labs. This study presents a modified PAC approach that has a higher success rate than other models and an 8-week postsurgery survival rate of 97.8%. This PAC approach provides a useful technique for studying the mechanism of RVF and will enable an increased understanding of RVF.

Here, we provide a useful approach for studying the mechanism of right ventricular failure. A more convenient and efficient approach to pulmonary artery constriction is established using surgical instruments made inhouse. In addition, methods to evaluate the quality of this approach by echocardiography and catheterization are provided.

小鼠肺动脉收缩引起的右心室衰竭及右心室功能评价

The mechanism of right ventricular failure (RVF) requires clarification due to the uniqueness, high morbidity, high mortality, and refractory nature of ...

生物学

<meta charset="utf8"></head><body>优化肺动脉束带以实现一致的右心衰竭诱导

Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia Using Pulmonary Artery Banding

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described.
Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung.
In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.

<meta charset="utf8"></head><body>使用肺动脉束带法的右侧心脏重塑和心律失常大鼠模型

Right heart failure (RHF) is characterized by right-sided cardiac dilation and hypertrophy, leading to ventricular and atrial malfunction. Cardiopulmonary conditions associated with RHF are accompanied by an increased risk for cardiac arrhythmias. This article describes a standardized model of pulmonary artery banding-induced RHF associated with enhanced ventricular and atrial arrhythmogenesis.