Name: hemodynamic characterization of rodent models of pulmonary arterial hypertension
Uploaded: 2016-04-11T14:00:00.000+00:00
Duration: 9 min 40 s
Description: Watch this Scientific Journal Video about Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension at JoVE.com

SR is supported by NIH K08HL114643, Gilead Research Scholars in Pulmonary Arterial Hypertension and a Burroughs Wellcome Fund Career Award for Medical Scientists.

中描述的所有程序遵循医学杜克大学医学院的动物护理准则。 1.在此之前启动程序注意:任何动物程序之前，确保已经获得适当的机构的许可。如同所有的程序，使用适当的止痛药，以确保没有任何动物的痛苦。 <ol><li>与肝素的无菌盐水（100单位/毫升）冲洗导管，以确保通畅。标记从导管等效于长度从心脏到颈部的中部的前端的点（约4cm老鼠和2厘米只小鼠）。 </li><li>麻醉小鼠或大鼠。麻醉剂的选择包括异氟烷（诱导3-4％，维持1.5％与100％的氧气的混合），氯胺酮/赛拉嗪（80-120 / 10毫克/千克）和戊巴比妥（40-80毫克/千克）6。 <ol><li>例如，用氯胺酮:赛拉嗪（80-120毫克/公斤:10-16毫克/千克IP进行小鼠和80-100毫克/公斤:5-10米克/千克IP进行鼠），以单剂量持续麻醉20-50分钟。超声心动图，麻醉小鼠或大鼠用异氟烷（诱导3-4％和维护1.5％）。按捏在啮齿动物手术区，以确认取款反射消失评估麻醉深度。使用于眼部兽医药膏，以防止干燥时的麻醉下。 注意:不同的麻醉剂可用于获得具有正确的使用和优化可靠的结果（综述别处6）。我们的导尿偏好是使用氯胺酮:甲苯噻嗪。过量用氯胺酮/赛拉嗪可能深刻地降低心脏速率和心功能，所以它是保持适当的温度和呼吸控制的关键。为了保持心脏小鼠率（&gt; 400 /分），我们经常进行双边迷走神经切断。氯胺酮/赛拉嗪的此处的量一般将最后20-30分钟，这是足以执行任一开闭胸心脏导管插入术，随后通过安乐死动物。 </li></ol></li><li>制备大鼠/小鼠的手术过程（ 图1）。 <ol><li>剃须从胸部皮毛（允许超声心动图），并从手术区，在右边的脖子上。 </li><li>从内向外的优碘的中心的圆形扫擦洗剃手术区域，接着用70％的酒精棉签清洁。 </li><li>将动物在手术平台下的一个暖垫。设定加热水平以维持体温的37-37.5℃。监测体温用直肠探针。低温可导致显著心动过速显著心动过缓和热疗结果。 </li></ol></li></ol> 2.超声心动图注:在其他地方7中描述的啮齿动物超声心动图的完整描述。为鼠标，前麻醉，可在清醒的，手动抑制动物获得的图像。对于大鼠，麻醉优选为大鼠之前心动过大，在清醒时手动抑制）。 <ol><li>胸骨旁长轴（PLAX）查看。 <ol><li>放置动物在平台上的仰卧姿势或手动抑制它。 </li><li>选择B模式投射二维实时图像。 </li><li>对准超声换能器40兆赫的鼠标或25兆赫的对大鼠的左胸骨旁线的频率，并然后旋转传感器逆时针30°与探针指示器在尾方向指向（5 11点线位置） 。角传感器略（沿同一断层平面中的换能器的短轴摇动），以获得在屏幕的中心的完整的低压室视图。 </li><li>找到并查看这些解剖结构（ 图2A）:左心室（LV）的内腔;室间隔（IVS）;右心室（RV）的管腔;升主动脉（AO）;和左心房（LA）。 </li> &lt;李&gt;切换到M模式下，一旦上述这些结构清晰可见。将通过利用AO作为参考点LV流明的最宽部分的指示线，也使左室腔（ 图2B）中央的聚焦深度谎言。通过改变传感器的角度和获取M模式下测量使RV的类似测量。 </li><li>用电影商店创建视频循环录制离线测量（LV腔尺寸，FS和左室壁厚度）的数据。 </li><li>通过将PW光标在主动脉和记录（ 图2C）取得在脉冲多普勒模式主动脉流出的多普勒跟踪。 </li></ol></li><li>胸骨旁短轴观（PSAX）在主动脉的水平。 <ol><li>切换到B模式。 </li><li>从胸骨旁长轴视图振子90°顺时针转动，得到胸骨旁短轴观（ 图3）。移动和角度传感器朝头盖骨为IDentify主动脉瓣横断面图。 </li><li>识别右室流出道（RVOT）作为定位于主动脉右上角月牙形结构，肺动脉瓣叶和肺动脉继续。 </li><li>握住手工同一位置稳定。切换到脉冲多普勒模式。 注意:用于保持啮齿动物和探针可以用于最小化换能器位置的移动和变形例的站台上。 </li><li>将样品体积近端肺动脉瓣的电平中的右心室流出道的中心，然后通过容器（ 图3B）平行于血液流动方向的光标定位。 注意:对采样角度调整到血液流动的方向，或使用超声软件以校正角度的变化是很重要的。未经校正，最大角度到容器为30°，其对应于速度的〜15％低估。 </li><li>形容词乌斯根据需要，得到"良好"的多普勒包络，它具有白色边框和暗中空内指示的层的血流（ 图3C）的比例（血流的速度）。记录多普勒跟踪。 注:一个"坏"多普勒信封不能容纳足够的白色边框，黑窟窿。 </li><li>如果在这个节骨眼上不进行导尿，允许如果使用麻醉啮齿动物恢复。直到它已经恢复了足够的意识，以保持胸骨斜卧，不交回公司的其他动物，直到其完全恢复，不要离开啮齿动物无人值守。如果进行导尿，请进入第3。 </li></ol></li></ol> 3.右心导管<ol><li>对于RV压力测量封闭胸方法<ol><li>建立: <ol><li>连接压力传感器输入通道1.在软件，设置通道1的压力和陈荫罴埃尔2心脏速率。 </li><li>到单位转换为毫米汞柱，记录基线轨迹，使用压力表手动（如果使用一个血压换能器和PE管）执行压力校准。然后执行下通道1单位换算。 </li><li>要设置心脏速率，关闭通道的输入2.选择下路2循环测量和选择源和速率测量通道1。 </li></ol></li><li>将鼠标/大鼠与深度的焦点和5倍的倍率解剖显微镜下。 </li><li>切割从下颌骨到胸骨（ 图1）的皮肤。放置一对拉钩到切口的每一侧以充分暴露出颈部区域。 </li><li>说白了解剖分离唾液腺，露出右颈外静脉用细钝尖镊子（ 图4A，B）。 </li><li>小心隔离从周围结缔组织右颈外静脉。 </li> &lt;li&gt;将丝线缝合两片（4-0老鼠; 6-0小鼠）右颈外静脉下方，结扎远端静脉（接近下颌骨越好），再扎一个松散的结近端（ 图4C）。 </li><li>使用虹膜剪，使一个小"缺口"（切）近端向远端打成结。 </li><li>握住镊子导管插入导管进入静脉切断，然后拧紧近端结。 注意:我们通常使用小鼠和聚乙烯（PE）-10油管（〜2星期五大小）的PE-50（〜3星期五大小）老鼠，其通过一个31 G或21g的针连接到常规压力传感器和校准。标记用标记在导管在一个长度大致对应于尖端放置在右心室。作为替代聚乙烯管材，可以使用微压计导管。轻轻拉动远端结可以帮忙介绍导管。 </li><li>轻轻推导管进入右心脏和监控根据标记的进​​步的深度。监控软件来验证导管位置，并确定RV压力压迹（ 图5）。 </li><li>保持导管动并收集数据（切换数据旁边的开始按钮记录）2分钟。 </li><li>继续样品采集（第四节）。 </li></ol></li><li>开胸方法对RV PV回路分析。 注意:不能以封闭胸腔方法由于电导导管，它不会从SVC传递到RA的刚度来执行右心室的光伏环分析。市售电导导管是专为LV光伏循环分析。 <ol><li>在设置通道1电导软件;通道2的压力;和信道3的心脏速率。 </li><li>插管与地下16聚四氟乙烯管大鼠和管连接到一个机械通气。计算并通过后续的设置通气参数为小鼠或大鼠ING公式6:潮气量（V T，毫升）= 6.2×M的1.01（M =动物质量，kg）;呼吸率（RR，分-1）= 53.5×M的-0.26（ 图6A）。 </li><li>蔓延70％乙醇到皮毛减少到手术区域毛皮的传播。 </li><li>让下面的xyphoid过程中的切口和双边剖析朝向侧面剪刀皮肤。 </li><li>穿过腹壁切割并通过沿隔膜双边夹层打开腹腔。 </li><li>打开隔膜暴露心脏的顶点和双边切肋骨（ 图6A）。通过喷雾盐水到使用注射器的胸椎和腹腔防止蒸发和组织的干燥。 注:我们通常用解剖剪打开腹腔和肋骨。出血通常是不显著的，但如果有出血，可以用电灼。 </li><li>仔细分离日从周围的结缔组织ê下腔静脉（IVC）。 </li><li>将一块丝线缝合（老鼠4-0; 6-0小鼠）周围的下腔静脉，再扎一个松散的结（或线程通过地下16聚四氟乙烯管缝合）（ 图6B）。 </li><li>穿刺平行于右室游离壁27-30号针头顶端RV游离壁并取出针。要小心，不要推针超过4毫米。 注意:可替换地，一小片的PE-60管，可用于指导电导导管穿刺到RV顶点。 </li><li>通过缠绕在心尖RV游离壁，直到所有电极是心室（ 图6C）内的刺插入电导导管末端。 </li><li>监控软件中的压力容积环，然后调整导管获得一致形循环，即不表现出显著的呼吸变化（ 图7B，C）的位置。 </li><li>记录基线PV循环（切换数据旁边的启动按钮录音）至少10秒获得了多项光伏循环。 </li><li>拉周围放置IVC缝线以改变预加载，并记录在PV环。分析离线数据并导出右心室收缩功能（ 图7D）的各种参数。此分析先前已8所述。 注:IVC可以备选地通过镊子闭塞。监控RV压迹，以确认预紧力的降低。 </li><li>如先前所描述，以允许从电导单位体积单位6转换执行盐水和试管校准。 </li><li>记录数据后，轻轻拉出导管和导管的末端放置立即与盐水的水浴中。在完成，清洁每制造商的说明在导管。 </li></ol></li></ol> 4.收集心脏和肺标本注意:这里的程序重新描述为终端，动物必须要么闭环或开胸右心脏导管插入后安乐死。 <ol><li>通过打开胸廓（双侧开胸）安乐死的小鼠如果使用封闭胸部的方式，血管扩张，或通过麻醉过量后关闭呼吸器。 注意:不建议颈椎脱位。 </li><li>为了进行肺灌注通胀，通胀管路连接到设置膨胀为20的水柱压力的肺部ringstand（但不要打开阀门尚未膨胀肺部）。 </li><li>说白了，从周围的肌肉和结缔组织解剖气管。 </li><li>将一块丝线缝合（老鼠4-0; 6-0小鼠）周围的气管，再扎一个松散的结。 </li><li>轻轻按下头部伸展气管，并进行切割（周长的70％）接近下颌骨。 </li><li>保持温柔的伸展并插入气管套管（20克的小鼠或大鼠为16 G）。固定用缝合插管。套管连接到通胀管和领带绕套管缝合，防止固定剂的回流。 </li><li>通过使用10毫升注射器刺伤右心室游离壁并朝肺动脉注入冲洗用PBS肺部。尼克一旦肺部开始变白左心房。 </li><li>通过在主动脉根部切割收获心脏。 </li><li>使用夹住一只蚊子止血肺的右下肺叶切右下肺叶。放置块放入离心管和捕捉在液氮中冷冻。 </li><li>膨胀，用10％缓冲的中性福尔马林肺5分钟并取出气管插管随后通过结扎气管。 </li><li>解剖肺出胸的，并用10％缓冲的中性福尔马林固定。 注意:可替换地，膨胀与最佳切割介质的肺（OCT中，1:1稀释，用PBS），并在未稀释十月冻结冰冻切片以后制备。 </li><li>小心分离从心室心房和通过解剖沿着室间隔隔离右心室游离壁。 </li><li>称量RV和LV +室间隔（LV + S）来计算富尔顿指数（RV / LV + S）9，它量化RV肥大的程度。 注:TheFulton指数PH不同型号而异。鼠10:控制，0.28±0.01;缺氧诱导，0.57±0.02; MCT处理，0.51±0.03。 C57BL6 / J小鼠11:控制，0.26±0.01; SuHx（14天），0.40±0.02; SuHx（21天），0.43±0.01; SuHx（28天），0.44±0.03。 </li><li>快冷冻在​​液氮中的休旅车和LV + S或在10％缓冲的中性福尔马林固定。 </li></ol>

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	<li>Gomez-Arroyo, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+brief+overview+of+mouse+models+of+pulmonary+arterial+hypertension:+problems+and+prospects.">A brief overview of mouse models of pulmonary arterial hypertension: problems and prospects.</a> Am J Physiol Lung Cell Mol Physiol. 302, 977-991 (2012).</li><li>Ryan, J. J., Marsboom, G., Archer, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rodent+models+of+group+1+pulmonary+hypertension.">Rodent models of group 1 pulmonary hypertension.</a> Handbook of experimental pharmacology. 218, 105-149 (2013).</li><li>Voelkel, N. F., Tuder, 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=Hypoxia-induced+pulmonary+vascular+remodeling:+a+model+for+what+human+disease.">Hypoxia-induced pulmonary vascular remodeling: a model for what human disease.</a> J Clin Invest. 106, 733-738 (2000).</li><li>Gomez-Arroyo, J. 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=The+monocrotaline+model+of+pulmonary+hypertension+in+perspective.">The monocrotaline model of pulmonary hypertension in perspective.</a> Am J Physiol Lung Cell Mol Physiol. 302, 363-369 (2012).</li><li>Abe, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formation+of+plexiform+lesions+in+experimental+severe+pulmonary+arterial+hypertension.">Formation of plexiform lesions in experimental severe pulmonary arterial hypertension.</a> Circulation. 121, 2747-2754 (2010).</li><li>Pacher, P., Nagayama, T., Mukhopadhyay, P., Batkai, S., Kass, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+cardiac+function+using+pressure-volume+conductance+catheter+technique+in+mice+and+rats.">Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.</a> Nat Protoc. 3, 1422-1434 (2008).</li><li>Brittain, E., Penner, N. L., West, J., Hemnes, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiographic+Assessment+of+the+Right+Heart+in+Mice.">Echocardiographic Assessment of the Right Heart in Mice.</a> J. Vis. Exp. (81), e50912 (2013).</li><li>Abraham, D. M., Mao, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+Pressure-Volume+Loop+Analyses+Using+Conductance+Catheters+in+Mice.">Cardiac Pressure-Volume Loop Analyses Using Conductance Catheters in Mice.</a> J Vis Exp. , (2015).</li><li>Vergadi, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+macrophage+recruitment+and+alternative+activation+are+critical+for+the+later+development+of+hypoxia-induced+pulmonary+hypertension.">Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension.</a> Circulation. 123, 1986-1995 (2011).</li><li>Mam, V., 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=Impaired+vasoconstriction+and+nitric+oxide-mediated+relaxation+in+pulmonary+arteries+of+hypoxia-+and+monocrotaline-induced+pulmonary+hypertensive+rats.">Impaired vasoconstriction and nitric oxide-mediated relaxation in pulmonary arteries of hypoxia- and monocrotaline-induced pulmonary hypertensive rats.</a> J Pharmacol Exp Ther. 332, 455-462 (2010).</li><li>Wang, Z., Schreier, D. A., Hacker, T. A., Chesler, N. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progressive+right+ventricular+functional+and+structural+changes+in+a+mouse+model+of+pulmonary+arterial+hypertension.">Progressive right ventricular functional and structural changes in a mouse model of pulmonary arterial hypertension.</a> Physiol Rep. 1, 00184 (2013).</li><li>Thibault, H. 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=Noninvasive+assessment+of+murine+pulmonary+arterial+pressure:+validation+and+application+to+models+of+pulmonary+hypertension.">Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension.</a> Circ Cardiovasc Imaging. 3, 157-163 (2010).</li><li>Abe, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+treatment+with+a+Rho-kinase+inhibitor+improves+monocrotaline-induced+fatal+pulmonary+hypertension+in+rats.">Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats.</a> Circ Res. 94, 385-393 (2004).</li><li>Ma, W., 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=hypoxia+chamer+info--Calpain+mediates+pulmonary+vascular+remodeling+in+rodent+models+of+pulmonary+hypertension,+and+its+inhibition+attenuates+pathologic+features+of+disease.">hypoxia chamer info--Calpain mediates pulmonary vascular remodeling in rodent models of pulmonary hypertension, and its inhibition attenuates pathologic features of disease.</a> J Clin Invest. 121, 4548-4566 (2011).</li><li>de Man, F. S., 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=Bisoprolol+delays+progression+towards+right+heart+failure+in+experimental+pulmonary+hypertension.">Bisoprolol delays progression towards right heart failure in experimental pulmonary hypertension.</a> Circ Heart Fail. 5, 97-105 (2012).</li><li>de Man, F. S., 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=Dysregulated+renin-angiotensin-aldosterone+system+contributes+to+pulmonary+arterial+hypertension.">Dysregulated renin-angiotensin-aldosterone system contributes to pulmonary arterial hypertension.</a> Am J Respir Crit Care Med. 186, 780-789 (2012).</li><li>Pritts, C. D., Pearl, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anesthesia+for+patients+with+pulmonary+hypertension.">Anesthesia for patients with pulmonary hypertension.</a> Curr Opin Anaesthesiol. 23, 411-416 (2010).</li><li>Paulin, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+miR-208-Mef2+Axis+Drives+the+Decompensation+of+Right+Ventricular+Function+in+Pulmonary+Hypertension.">A miR-208-Mef2 Axis Drives the Decompensation of Right Ventricular Function in Pulmonary Hypertension.</a> Circ Res. 116, 56-69 (2015).</li><li>Brittain, E., Penner, N. L., West, J., Hemnes, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiographic+assessment+of+the+right+heart+in+mice.">Echocardiographic assessment of the right heart in mice.</a> J Vis Exp. , (2013).</li><li>Cheng, H. W., 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=Assessment+of+right+ventricular+structure+and+function+in+mouse+model+of+pulmonary+artery+constriction+by+transthoracic+echocardiography.">Assessment of right ventricular structure and function in mouse model of pulmonary artery constriction by transthoracic echocardiography.</a> J Vis Exp. , e51041 (2014).</li></ol>

The authors have nothing to disclose.

The protocols outlined here describe a comprehensive characterization of hemodynamics and right ventricular function in rodent models of pulmonary hypertension. While right heart catheterization as described here is a terminal procedure, the mortality associated with echocardiography is minimal, which allows for screening and follow-up of disease progression. However, similar to patients with PH having markedly increased mortality with anesthesia17, in our experience, rats with severe PH do not tolerate anesth...

肺动脉高压（PAH）是炎性细胞浸润，平滑肌细胞增殖和内皮细胞凋亡相关联的肺血管的疾病。这些变化导致肺小动脉闭塞，随后导致右心室（RV）功能障碍和心脏衰竭。为了了解病理生理学的基本PAH PAH和右心衰竭，多个不同的模型，包括基因和药理学的模型，为研究这种疾病已经发展（综述别处1,2）。 这些模型的，最流行的是在小鼠低氧诱导（HX）PAH和野百合碱（MCT）和在大鼠SU5416缺氧（SuHx）模型。在小鼠HX模型，小鼠被暴露到4周缺氧（无论是常压或低压，对应于18000英尺的0.10的FiO2高度），与内侧扩散所得的发展，增加RV SYST奥利奇压力和RV肥大3的发展。 MCT在通过一个不明确的机制，然后导致PAH 4的发展在损伤肺的内皮细胞60毫克/公斤的结果的单剂量。 SU5416是血管内皮生长因子受体（VEGFR）1和2阻断剂的抑制剂，并用单次皮下注射60毫克/千克，随后通过暴露于慢性缺氧3周导致永久肺动脉高血压具有相似病理改变治疗到出现在人类疾病，闭塞性血管病变5的形成。在过去几年中，对肺动脉高血压几个转基因小鼠模型已被开发。这些包括敲除和骨形态发生蛋白受体2（BMPR2）的突变，如BMPR2基因突变在PAH的两个家族和特发性形式存在，血红素氧合酶1敲除和IL-6的过度表达（别处1,2-综述）。 PH这些不同的啮齿动物模型有不同程度的肺动脉高压，右心室肥厚和右心衰竭。而缺氧和各种转基因小鼠模型导致比任一大鼠模型1温和得多的PAH，它允许不同的基因突变和其相关的分子信号转导途径的测试。在MCT模型并导致严重的肺动脉高压，虽然MCT似乎是有毒的内皮细胞在多种组织4。该SuHx模型的特征是血管变化更加类似于在人类原发性肺动脉高压看出，虽然需要同时药理操纵和缺氧曝光。此外，在所有这些模型中，可能存在与PAH的发展相关的组织病理学变化，肺动脉压和右心室功能之间的断开。这是相对于人类疾病，其中通常有病理变化之间的比例关系，pulmon的严重性元高血压和右心衰竭的程度。因此，PH这些啮齿动物模型的综合表征是必需的，涉及到RV功能（通常通过超声心动图）的评估，血液动力学（心导管）和心脏​​组织病理学和肺（从组织收获）。 在这个协议中，我们描述了用于在大鼠和小鼠的PAH模型的血流动力学表征的基本技术。这些常规技术可以应用到右心室和肺血管的任何研究，并且不限于PAH的模型。通过超声心动图可视化RV是以大鼠相对简单，但在小鼠中更有挑战性，因为它们的大小和RV的复杂几何形状。此外，用于定量RV功能的一些替代物，比如TAPSE，肺动脉（PA）的加速时间和PA血流频谱开槽，不能很好的在人类验证，并用PU的相关评估只是弱lmonary高血压和血流动力学侵入RV功能。右心室血流动力学的确定是最好的一个封闭胸完成，以保持与灵感负胸内压力的影响，虽然开胸导尿使用阻抗导管允许压力容积（PV）的判定回路和更详细的血流动力学的表征。如同任何程序，开发经验与程序，是实验成功的关键。

<table><tbody><tr><td>Vevo 2100 Imaging System (120V)&amp;nbsp;</td><td>VisualSonics, inc.&amp;nbsp;</td><td>VS-11945</td><td></td></tr><tr><td>Vevo 2100 Imaging Station&amp;nbsp;</td><td>VisualSonics, inc.&amp;nbsp;</td><td></td><td></td></tr><tr><td>High-frequency Mechanical Transducers</td><td>VisualSonics, inc.&amp;nbsp;</td><td>MS250, MS550D, MS400</td><td></td></tr><tr><td>Ultrasound Gel Parker&amp;nbsp;</td><td>Laboratories Inc.&amp;nbsp;</td><td>01-08</td><td></td></tr><tr><td>PowerLab 4/35</td><td>ADInstruments</td><td>ML765</td><td></td></tr><tr><td>Labchart 8</td><td>ADInstruments</td><td></td><td></td></tr><tr><td>BP transducer with stopcock and cable</td><td>ADInstruments</td><td>MLT1199</td><td></td></tr><tr><td>BP transducer calibration kit</td><td>ADInstruments</td><td>MLA1052</td><td></td></tr><tr><td>Mikro-Tip Pressure Catheter for mouse</td><td>Millar</td><td>SPR-1000</td><td>Alternative catheter available from Scisense FT111B (mouse) and FT211B (rat)</td></tr><tr><td>Mikro-Tip Pressure Catheter for rat</td><td>Millar</td><td>SPR-513</td><td>Alternative catheter available from Scisense FT111B (mouse) and FT211B (rat)</td></tr><tr><td>Millar Mikro-Tip&amp;nbsp;ultra-miniature PV loop catheter for mice</td><td>Millar</td><td>PVR-1035</td><td>Alternative catheter available from Scisense FT112 (mouse)</td></tr><tr><td>Millar Mikro-Tip ultra miniature PV loop catheter for rats</td><td>Millar</td><td>SPR-869</td><td>Alternative catheter available from Scisense FT112 (mouse)</td></tr><tr><td>Millar PV system MPVS-300&amp;nbsp;</td><td>Millar</td><td>MPVS-300</td><td></td></tr><tr><td>4-0 Silk Black Braid 100 Yard Spool</td><td>Roboz Surgical</td><td>SUT-15-2</td><td></td></tr><tr><td>6-0 Silk Black Braid 100 Yard Spool</td><td>Roboz Surgical</td><td>SUT-14-1</td><td></td></tr><tr><td>Iris Scissors, Delicate, Integra Miltex</td><td>VWR</td><td>21909-248</td><td></td></tr><tr><td>VWR Dissecting Scissors, Sharp/Blunt Tip</td><td>VWR</td><td>82027-588</td><td></td></tr><tr><td>VWR Delicate Scissors, 4 1/2&quot;</td><td>VWR</td><td>82027-582</td><td></td></tr><tr><td>Two star Hemostats, Excelta</td><td>VWR</td><td>63042-090</td><td></td></tr><tr><td>Neutral-buffered formalin</td><td>VWR</td><td>89370-094</td><td></td></tr><tr><td>Crotaline</td><td>Sigma</td><td>C2401</td><td></td></tr><tr><td>SU5416</td><td>Tocris Biosciences</td><td>3037</td><td></td></tr><tr><td>3.5X-45X Boom Stand Trinocular Zoom Stereo Microscope&amp;nbsp;</td><td>AmScope</td><td>SM-3BX</td><td></td></tr><tr><td>PE (Polyethylene Tubing)-10</td><td>Braintree Scientific Inc</td><td>PE10 36 FT</td><td></td></tr><tr><td>PE (Polyethylene Tubing)-50</td><td>Braintree Scientific Inc</td><td>PE50 36 FT</td><td></td></tr><tr><td>PE (Polyethylene Tubing)-60</td><td>Braintree Scientific Inc</td><td>PE60 36 FT</td><td></td></tr><tr><td>Tabletop Isoflurane Anesthesia Unit</td><td>Kent Scientific</td><td>ACV-1205S</td><td></td></tr><tr><td>Surgisuite multi-functional surgical platform</td><td>Kent Scientific</td><td>Surgisuite</td><td></td></tr><tr><td>Retractor set</td><td>Kent Scientific</td><td>SURGI-5002</td><td></td></tr><tr><td>Anesthesia induction chamber</td><td>VetEquip</td><td>941443</td><td></td></tr><tr><td>Anesthesia Gas filter canister</td><td>Kent Scientific</td><td>ACV-2001</td><td></td></tr><tr><td>Rodent nose cone</td><td>VetEquip</td><td>921431</td><td></td></tr></tbody></table>

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.

由于在啮齿类动物中右心脏导管插入术通常是不适用于纵向后续终端程序，超声心动图是筛查和随访12极好的无创性的选择。而在人类PAH肺动脉收缩压超声心动图通常是从三尖瓣关闭不全，通常是简单的顶视图中获得的衍生，是不是在啮齿类动物中获得可靠这样的观点，防止由多普勒肺动脉收缩压的估计。然而，在主动脉级PSAX视图可以容易地在啮齿类动物中，这使得记录和测量肺动脉多?...

Watch this Scientific Journal Video about Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension at JoVE.com

Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

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 ...

hemodynamic-characterization-rodent-models-pulmonary-arterial

Research

JoVE Journal

Medicine

20.9K 次观看.  Duke University Medical Center. 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.

视频: Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension

Right Ventricular Systolic Pressure Measurements in Combination with Harvest of Lung and Immune Tissue Samples in Mice

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes 1.
Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes. Increased pulmonary artery pressures are associated with increased pressure in the lung vascular bed and pulmonary hypertension 2. Pulmonary hypertension is often associated with inflammatory lung diseases, for example chronic obstructive pulmonary disease, or autoimmune diseases 3. Because pulmonary hypertension confers a bad prognosis for quality of life and life expectancy, much research is directed towards understanding the mechanisms that might be targets for pharmaceutical intervention 4. The main challenge for the development of effective management tools for pulmonary hypertension remains the complexity of the simultaneous understanding of molecular and cellular changes in the right heart, the lungs and the immune system.
Here, we present a procedural workflow for the rapid and precise measurement of pressure changes in the right heart of mice and the simultaneous harvest of samples from heart, lungs and immune tissues. The method is based on the direct catheterization of the right ventricle via the jugular vein in close-chested mice, first developed in the late 1990s as surrogate measure of pressures in the pulmonary artery5-13. The organized team-approach facilitates a very rapid right heart catheterization technique. This makes it possible to perform the measurements in mice that spontaneously breathe room air. The organization of the work-flow in distinct work-areas reduces time delay and opens the possibility to simultaneously perform physiology experiments and harvest immune, heart and lung tissues.
The procedural workflow outlined here can be adapted for a wide variety of laboratory settings and study designs, from small, targeted experiments, to large drug screening assays. The simultaneous acquisition of cardiac physiology data that can be expanded to include echocardiography5,14-17 and harvest of heart, lung and immune tissues reduces the number of animals needed to obtain data that move the scientific knowledge basis forward. The procedural workflow presented here also provides an ideal basis for gaining knowledge of the networks that link immune, lung and heart function. The same principles outlined here can be adapted to study other or additional organs as needed.

A specific and rapid protocol to simultaneously investigate right heart function, lung inflammation, and the immune response is described as a learning tool. Video and figures describe physiology and microdissection techniques in an organized team-approach that is adaptable to be used for small to large sized studies.

右心室收缩压测量组合在小鼠的肺和免疫组织样品的收获

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is ...

科研

免疫与感染

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 ...

医学

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.

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 ...

Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats

This is a detailed protocol describing invasive hemodynamic measurements in cirrhotic rats for the characterization of portal hypertensive syndrome. Portal hypertension (PHT) due to cirrhosis is responsible for the most severe complications in patients with liver disease. The full picture of the portal hypertensive syndrome is characterized by increased portal pressure (PP) due to the increased intrahepatic vascular resistance (IHVR), hyperdynamic circulation, and increased splanchnic blood flow. Progressive splanchnic arterial vasodilation and increased cardiac output with elevated heart rate (HR) but low arterial pressure characterizes the portal hypertensive syndrome.
Novel therapies are currently being developed that aim to decrease PP by either targeting IHVR or increased splanchnic blood flow &#8212; but side effects on systemic hemodynamics may occur. Thus, a detailed characterization of portal venous, splanchnic, and systemic hemodynamic parameters, including measurement of PP, portal venous blood flow (PVBF), mesenteric arterial blood flow, mean arterial pressure (MAP), and HR is needed for preclinical evaluation of the efficacy of novel treatments for PHT. Our video article provides the reader with a structured protocol for performing invasive hemodynamic measurements in cirrhotic rats. In particular, we describe the catheterization of the femoral artery and the portal vein via an ileocolic vein and the measurement of portal venous and splanchnic blood flow via perivascular Doppler-ultrasound flow probes. Representative results of different rat models of PHT are shown.

Here we describe a detailed protocol for invasive measurements of hemodynamic parameters including portal pressure, splanchnic blood flow, and systemic hemodynamics in order to characterize the portal hypertensive syndrome in rats.

肝硬化大鼠门脉高压综合征的侵袭性血流动力学特征

This is a detailed protocol describing invasive hemodynamic measurements in cirrhotic rats for the characterization of portal hypertensive syndrome. ...

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 ...

Induction and Characterization of Pulmonary Hypertension in Mice using the Hypoxia/SU5416 Model

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by right heart&#160;catheterization. A broad spectrum of diseases can lead to PH, differing in their etiology, histopathology, clinical presentation, prognosis, and response to&#160;treatment. Despite significant progress in the last years, PH remains an uncured disease. Understanding the underlying mechanisms can pave the way for the development of new therapies. Animal models are important research tools to achieve this goal. Currently, there are several models available for recapitulating PH. This protocol describes a two-hit mouse PH model. The stimuli for PH development are hypoxia and the injection of SU5416, a vascular endothelial growth factor (VEGF) receptor antagonist. Three weeks after initiation of Hypoxia/SU5416, animals develop pulmonary vascular remodeling imitating the histopathological changes observed in human PH (predominantly Group 1). Vascular remodeling in the pulmonary circulation results in the remodeling of the right&#160;ventricle (RV). The procedures for measuring RV pressures (using the open chest method), the morphometrical analyses of the RV (by dissecting and weighing both cardiac ventricles) and the histological assessments of the remodeling (both pulmonary by assessing vascular remodeling and cardiac by assessing RV cardiomyocyte hypertrophy and fibrosis) are described in detail. The advantages of this protocol are the possibility of the application both in wild type and in genetically modified mice, the relatively easy and low-cost implementation, and the quick development of the disease of interest (3 weeks). Limitations of this method are that mice do not develop a severe phenotype and PH is reversible upon return to normoxia. Prevention, as well as therapy studies, can easily be implemented in this model, without the necessity of advanced skills (as opposed to surgical rodent models).

This protocol describes the induction of pulmonary hypertension (PH) in mice based on the exposure to hypoxia and the injection of a VEGF receptor antagonist. The animals develop PH and right ventricular (RV) hypertrophy 3 weeks after the initiation of the protocol. The functional and morphometrical characterization of the model is also presented.

使用缺氧/SU5416模型对小鼠的肺高血压进行诱导和特征

Pulmonary Hypertension (PH) is a pathophysiological condition, defined by a mean pulmonary arterial pressure exceeding 25 mm Hg at rest, as assessed by ...

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. ...

Multiple Intravenous Bolus Dosing and Invasive Hemodynamic Assessment in a Hypoxia-Induced Mouse Pulmonary Artery Hypertension Model

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, there is no cure for PAH. It is important to discover new compounds that can be used to treat PAH. The mouse hypoxia-induced PAH model is a widely used model for PAH research. This model recapitulates human clinical manifestations of PAH Group 3 disease and is an important research tool to evaluate the effectiveness of new experimental therapies for PAH. Research using this model often requires the administration of compounds in mice. For a compound that needs to be given directly into the bloodstream, optimizing intravenous (IV) administration is a key part of the experimental procedures. Ideally, the IV injection system should permit multiple injections over a set time course. Although the mouse hypoxia-induced PAH model is very popular in many laboratories, it is technically challenging to perform multiple IV bolus dosing and invasive hemodynamic assessment in this model. In this protocol, we present step-by-step instructions on how to carry out multiple IV bolus dosing via mouse jugular vein and perform arterial and right ventricle catheterization for hemodynamic assessment in mouse hypoxia-induced PAH model.

This protocol provides a step-by-step procedure for executing multiple intravenous bolus dose administration and invasive hemodynamic monitoring in mice. Investigators can use this protocol for future therapeutic compound screening for pulmonary artery hypertension.

缺氧诱导小鼠肺动脉高压模型中的多次静脉推注给药和侵入性血流动力学评估

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease, primarily affecting small pulmonary arterioles of the lung. Currently, ...

通过肺干带创建 RV 肥大和衰竭的小鼠模型

A Murine Model of Pressure Overload-Induced Right Ventricular Hypertrophy and Failure by Pulmonary Trunk Banding

Right ventricular (RV) failure caused by pressure overload is strongly associated with morbidity and mortality in a number of cardiovascular and pulmonary diseases. The pathogenesis of RV failure is complex and remains inadequately understood. To identify new therapeutic strategies for the treatment of RV failure, robust and reproducible animal models are essential. Models of pulmonary trunk banding (PTB) have gained popularity, as RV function can be assessed independently of changes in the pulmonary vasculature.
In this paper, we present a murine model of RV pressure overload induced by PTB in 5-week-old mice. The model can be used to induce different degrees of RV pathology, ranging from mild RV hypertrophy to decompensated RV failure. Detailed protocols for intubation, PTB surgery, and phenotyping by echocardiography are included in the paper. Furthermore, instructions for customizing instruments for intubation and PTB surgery are given, enabling fast and inexpensive reproduction of the PTB model.
Titanium ligating clips were used to constrict the pulmonary trunk, ensuring a highly reproducible and operator-independent degree of pulmonary trunk constriction. The severity of PTB was graded by using different inner ligating clip diameters (mild: 450 &#181;m and severe: 250 &#181;m). This resulted in RV pathology ranging from hypertrophy with preserved RV function to decompensated RV failure with reduced cardiac output and extracardiac manifestations. RV function was assessed by echocardiography at 1 week and 3 weeks after surgery. Examples of echocardiographic images and results are presented here. Furthermore, results from right heart catheterization and histological analyses of cardiac tissue are shown.

作者聚焦:研究肺动脉高压右心室衰竭的潜在机制

We describe a murine model of right ventricular pressure overload-induced by pulmonary trunk banding. Detailed protocols for intubation, surgery, and phenotyping by echocardiography are included in the paper. Custom-made instruments are used for intubation and surgery, allowing for fast and inexpensive reproduction of the model.

压力超负荷诱导的肺干束带右心室肥厚和衰竭的小鼠模型

Right ventricular (RV) failure caused by pressure overload is strongly associated with morbidity and mortality in a number of cardiovascular and pulmonary ...

肺动脉高压的啮齿动物模型的血流动力学特性

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此视频中的章节

右心室收缩压测量组合在小鼠的肺和免疫组织样品的收获

右心小鼠的超声心动图评价

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

肝硬化大鼠门脉高压综合征的侵袭性血流动力学特征

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

使用缺氧/SU5416模型对小鼠的肺高血压进行诱导和特征

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

缺氧诱导小鼠肺动脉高压模型中的多次静脉推注给药和侵入性血流动力学评估

压力超负荷诱导的肺干束带右心室肥厚和衰竭的小鼠模型

压力超负荷诱导的肺干束带右心室肥厚和衰竭的小鼠模型