作者要感谢皇后大学动物设施个人的帮助和合作。作者要感谢TMED硕士候选人Austin Read的帮助。
这项研究部分得到了美国国立卫生研究院 （NIH） 资助 NIH 1R01HL113003-01A1 （S.L.A.）、NIH 2R01HL071115-06A1 （SLA）、加拿大创新基金会和女王心肺科 （QCPU） 229252 和 33012 （SLA）、加拿大线粒体动力学和转化医学 950-229252 （SLA） 一级加拿大研究主席、加拿大卫生研究院 （CIHR） 基金会资助 CIHR FDN 143261， William J. Henderson 基金会 （S.L.A.）、加拿大血管网络学者奖 （F.P.） 和加拿大肺动脉高压协会 （F.P.） 的帕罗亚家庭奖学金

所有实验均按照女王大学生物安全和伦理准则（ROMEO/TRAQ#6016826）进行。所遵循的程序是按照机构准则执行的。这是一个终端程序。由于左右导管插入术的侵入性，应在数据采集后立即对动物实施安乐死。 安乐死应根据该机构的动物研究指南进行。
1. 实验准备和设置
<ol><li>在开始实验前30分钟，将导管放入含有生理盐水/肝素的10mL注射器中（图1A）。</li>
	<li>30 分钟后，根据制造商的建议校准导管（例如，基线和采集系统）。采集系统显示高校准值和低校准值，用于在开始实验之前校准采集系统。输出这些值并确保它们匹配。<ol><li>使用"压力平衡控制"、"粗略 +/-"或"精细 +/-"按钮将基线压力值设置为零。</li>
		<li>对高信号和低信号执行两点校准。<ol><li>在控制台上，按"导管菜单"中的"系统设置"。</li>
			<li>按"系统设置菜单"中的"发送校准信号"发送低信号。确保压力、体积、相位和幅度分别为 0 mm Hg、0 μL、0° 和 0 μs。</li>
			<li>按"Enter"发送高信号。确保压力、体积、相位和幅度分别为 100 mm Hg、150 μL、20° 和 5,000 μs。</li>
			<li>按"Enter"返回"系统设置菜单"。</li>
			<li>按"6"返回"导管菜单"。然后按"获取数据"。</li>
		</ol></li>
	</ol></li>
	<li>将 30 G 针弯曲至约 90°（图 1B、C）。这根弯曲的针将用于刺穿颈动脉和颈动脉血管。</li>
</ol>2.麻醉和体温控制
<ol><li>将小鼠（28g，本协议中的C57BL / 6）放入含有麻醉气体（即氧气100%，异氟烷3-4%用于诱导）的麻醉室中。</li>
	<li>当动物被麻醉时，对爪子或尾巴捏合没有反应，将小鼠仰卧在设定在37°C的加热垫上。</li>
	<li>通过鼻锥将鼠标连接到呼吸器，鼻锥提供 100% 氧气和 2% 异氟醚的混合物。要自动计算推荐的通气设置，请使用触摸屏将动物的体重输入呼吸机的专有软件。计算使用以下公式: 潮气量 = 6.2 x 动物质量1.01 （kg）， 呼吸速率 = 53.5 x 动物质量 - 0.26 （kg）。</li>
	<li>打开从麻醉室到鼻锥的麻醉管路。</li>
	<li>将温度反馈探头插入直肠，将垫探头插入垫和鼠标背面之间，将所需体温设置为 37 °C–37.5 °C。 在监视器屏幕上控制动物的温度（图2A，B）。</li>
	<li>使用手术胶带将小鼠的前爪和一只远端爪子粘在加热毯上，让一只后爪自由地监测麻醉深度。</li>
</ol>3. 手术部位访问
<ol><li>从手骨到舌骨水平进行 2 cm H 形腹侧颈椎中线切口。<ol><li>将皮肤反射到远离底层肌肉的地方。如果需要，可以切除这些肌肉以获得更好的可视化效果。</li>
		<li>轻轻地将下颌下腺移到一边。</li>
		<li>使用钝解剖方法解剖颈部软组织，并用镊子暴露胸锁乳突肌和胸骨舌骨肌。</li>
		<li>将筋膜从中间分开，覆盖成对的胸骨舌骨。让成对的胸骨舌骨横向缩回以暴露气管。注意不要损伤颈动脉和迷走神经，它们沿着气管运行。</li>
	</ol></li>
	<li>将镊子放在气管下方以抬高气管。然后，将 4.0 手术丝线穿过气管下方，并在缝合线中间打一个潜在的结，稍后将其收紧以固定气管插管（图 3A）。</li>
	<li>用剪刀在喉部水平以下的气管软骨环之间做一个小切口。插入气管插管（图3B）。</li>
	<li>将气管切开插管连接到呼吸器，然后开始用 100% 氧气和 2% 异氟烷通气。拧紧气管周围的结以固定气管插管，并将呼吸器管固定在手术台上。确保气管没有阻塞或塌陷（图3C）。</li>
</ol>4.右颈动脉和右颈动脉隔离
<ol><li>右颈动脉隔离<ol><li>使用钝性夹层，将胸骨舌骨肌外侧移位，以暴露和隔离右颈动脉。</li>
		<li>使用镊子钝性解剖将颈动脉与迷走神经隔离。</li>
		<li>在颈动脉下方通过三根手术缝合线 （4.0），不包括迷走神经。</li>
	</ol></li>
	<li>颈右静脉隔离<ol><li>将下颌下腺和腮腺向外侧移位，以观察右颈静脉。用镊子钝性解剖并暴露右颈静脉。小心地解剖静脉并去除周围的筋膜。</li>
		<li>将镊子穿过颈静脉下方。</li>
		<li>将一根手术缝合线穿过颈静脉下方，然后将其绑在静脉的颅侧。使用止血夹沿头部方向轻轻牵引该缝合线。</li>
		<li>在颈静脉下方再缝两根缝合线。使用止血钳沿尾部方向轻轻拉动最远端的缝合线。在中间缝合线打一个松散的潜在结。</li>
		<li>在预期的静脉切开部位将几滴温热的生理生理盐水滴在血管上。</li>
	</ol></li>
</ol>5. 右心室和左心室导管插入术的外科手术
<ol><li>右心室导管插入术（图 4 A-D）。<ol><li>使用立体显微镜，识别颈静脉。</li>
		<li>轻轻地对静脉施加卓越的牵引力。通过在颅缝线和中间缝合线之间插入 30 G 弯曲针进行静脉切开术。将针头相对于静脉以 140° 角插入，以确保其以同轴方式进入。</li>
		<li>插入时，通过移动针头来扩张静脉切开术。将导管尖端插入针头下方的静脉切开术中。然后轻轻系好中间缝合线，固定导管。 注意:要格外小心，不要将缝合线绑得太紧，因为用力过大会损坏导管。</li>
		<li>松开尾部缝合线，将导管推进到右心室，在连续监护仪上检测经典的右心室压力波形。</li>
		<li>稳定右心室压。确保导管在右心室中的正确定位，以产生最佳的 PV 回路。<ol><li>稳定反映血液和肌肉的幅度，以产生压力大小环（即 Y 轴压力、X 轴大小）。如果需要，轻轻旋转导管轴，使导管沿右心室轴线达到最佳位置。 注意: 反映肌肉的最大相位值应低于 7°。</li>
		</ol></li>
		<li>当压力大小环路信号最佳时，在采集过程中按控制台上的"Enter"键以执行基线扫描。确保监护仪屏幕上报告的心率（以每分钟心跳次数 （bpm） 为单位）在生理范围内（即 400-600 bpm）。</li>
		<li>生成 PV 回路。将"Magnitude"更改为"Volume"作为X轴的参数，并将压力保留为Y轴。当 PV 环路信号最优时，记录 30 秒。</li>
		<li>停止录制。拉回导管并用纱布轻轻擦拭。将导管放入肝素/氯化钠溶液中，并系扎尾部缝合线以止颈静脉出血。</li>
	</ol></li>
	<li>左心室导管插入术（图5 A-D）。<ol><li>轻轻地抬高右颈动脉，该右颈动脉先前通过在动脉下方滑动弯曲的镊子被隔离 （5A）。</li>
		<li>绑上先前的缝合线，从而闭塞动脉。然后，使用止血钳轻轻施加颅骨定向牵引。</li>
		<li>使用止血夹沿尾部方向拉动最远端的缝合线。在中间缝合线上打一个松散的电位结。</li>
		<li>在预期的动脉切开术部位的血管上滴几滴温热的生理盐水。使用立体定位显微镜聚焦于尾部和中缝合线之间的颅骨部分。</li>
		<li>轻轻地对动脉施加超强的牵引力。进行动脉切开术，在颅缝线和中间缝合线之间插入一根 30 G 的弯曲针。将针头相对于动脉 140° 插入，以确保其以同轴方式进入。</li>
		<li>将导管尖端插入动脉切开术，然后拧紧中间缝合线以固定导管。同时，松开远端缝合线，将导管推进主动脉以开始记录。确保压力通道显示典型的主动脉轨迹。</li>
		<li>将导管逆行穿过主动脉瓣进入左心室。从主动脉舒张压突然明显下降可以明显看出进入左心室。</li>
		<li>稳定左心室压。确保导管在左心室中的正确定位，以产生最佳的 PV 环。<ol><li>稳定反映血液和肌肉的幅度，以产生压力大小环（即 Y 轴压力、X 轴大小）。如果需要，轻轻旋转导管轴，以达到导管沿左心室轴线的最佳位置。 注意: 反映肌肉的最大相位值应低于 7°。</li>
		</ol></li>
		<li>停止录制。拉回导管并将其放入肝素/氯化钠溶液中。然后绑上尾部缝合线。</li>
		<li>用酶清洁剂（例如内嘈杂剂）清洁导管。 注意:手术后，根据该机构的动物研究指南对动物实施安乐死。 </li>
	</ol></li>
</ol>6. 数据分析
<ol><li>根据既定建议执行光伏回路分析。<ol><li>选择最佳压力-体积迹线（理想情况下是完整、稳定的 30 秒记录）。在软件上，单击"高级"，单击"循环"，然后单击"离线计算"。</li>
		<li>选择体积作为体积通道，选择压力作为压力通道。</li>
		<li>为了获得一致的结果，至少需要 20 个循环。</li>
	</ol></li>
</ol>

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<li>Ibrahim, E. -S. H., Bajwa, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Severe+Pulmonary+Arterial+Hypertension%3A+Comprehensive+Evaluation+by+Magnetic+Resonance+Imaging%5BTitle%5D)+AND+%22Case+Reports+in+Radiology%22%5BJournal%5D)">Severe Pulmonary Arterial Hypertension: Comprehensive Evaluation by Magnetic Resonance Imaging.</a> Case Reports in Radiology. 2015, 946920(2015).</li>
<li>Pinsky, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+right+ventricle%3A+interaction+with+the+pulmonary+circulation%5BTitle%5D)+AND+%22Critical+Care%22%5BJournal%5D)">The right ventricle: interaction with the pulmonary circulation.</a> Critical Care. 20 (1), London, England. 266(2016).</li>
<li>Kosova, E., Ricciardi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Cardiac+Catheterization%5BTitle%5D)+AND+%22JAMA%22%5BJournal%5D)">Cardiac Catheterization.</a> JAMA. 317 (22), 2344(2017).</li>
<li>Lindqvist, P., Calcutteea, A., Henein, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Echocardiography+in+the+assessment+of+right+heart+function%5BTitle%5D)+AND+%22European+Journal+of+Echocardiography%22%5BJournal%5D)">Echocardiography in the assessment of right heart function.</a> European Journal of Echocardiography. 9 (2), 225-234 (2007).</li>
<li>Fogel, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Assessment+of+Cardiac+Function+by+Magnetic+Resonance+Imaging%5BTitle%5D)+AND+%22Pediatric+Cardiology%22%5BJournal%5D)">Assessment of Cardiac Function by Magnetic Resonance Imaging.</a> Pediatric Cardiology. 21 (1), 59-69 (2000).</li>
<li>Janardhanan, R., Kramer, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Imaging+in+hypertensive+heart+disease%5BTitle%5D)+AND+%22Expert+Review+of+Cardiovascular+Therapy%22%5BJournal%5D)">Imaging in hypertensive heart disease.</a> Expert Review of Cardiovascular Therapy. 9 (2), 199-209 (2011).</li>
<li>Attili, A. K., Schuster, A., Nagel, E., Reiber, J. H. C., vander Geest, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Quantification+in+cardiac+MRI%3A+advances+in+image+acquisition+and+processing%5BTitle%5D)+AND+%22The+International+Journal+of+Cardiovascular+Imaging%22%5BJournal%5D)">Quantification in cardiac MRI: advances in image acquisition and processing.</a> The International Journal of Cardiovascular Imaging. 26 (1), 27-40 (2010).</li>
<li>Urboniene, D., Haber, I., Fang, Y. -H., Thenappan, T., Archer, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Validation+of+high-resolution+echocardiography+and+magnetic+resonance+imaging+vs.+high-fidelity+catheterization+in+experimental+pulmonary+hypertension%5BTitle%5D)+AND+%22American+Journal+of+Physiology-Lung+Cellular+and+Molecular+Physiology%22%5BJournal%5D)">Validation of high-resolution echocardiography and magnetic resonance imaging vs. high-fidelity catheterization in experimental pulmonary hypertension.</a> American Journal of Physiology-Lung Cellular and Molecular Physiology. 299 (3), 401-412 (2010).</li>
<li>Ashton, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Anatomical+and+functional+imaging+of+myocardial+infarction+in+mice+using+micro-CT+and+eXIA+160+contrast+agent%5BTitle%5D)+AND+%22Contrast+Media+%26+Molecular+Imaging%22%5BJournal%5D)">Anatomical and functional imaging of myocardial infarction in mice using micro-CT and eXIA 160 contrast agent.</a> Contrast Media & Molecular Imaging. 9 (2), 161(2014).</li>
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<li>Lindsey, M. L., Kassiri, Z., Virag, J. A. I., de Castro Brás, L. E., Scherrer-Crosbie, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Guidelines+for+measuring+cardiac+physiology+in+mice%5BTitle%5D)+AND+%22American+Journal+of+Physiology-Heart+and+Circulatory+Physiology%22%5BJournal%5D)">Guidelines for measuring cardiac physiology in mice.</a> American Journal of Physiology-Heart and Circulatory Physiology. 314 (4), 733-752 (2018).</li>
<li>Townsend, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Measuring+Pressure+Volume+Loops+in+the+Mouse%5BTitle%5D)+AND+%22Journal+of+Visualized+Experiments+JoVE%22%5BJournal%5D)">Measuring Pressure Volume Loops in the Mouse.</a> Journal of Visualized Experiments JoVE. (111), e53810(2016).</li>
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</ol>

心脏功能评估是临床前心血管和肺血管研究的关键步骤。在这项工作中，我们提出了一种用于小鼠心脏功能的封闭式胸部双心室评估方案。通过这种方法，可以在同一只小鼠中生成右心室和左心室PV环。这种方法可以对心脏功能进行可靠而完整的评估，从而可以测量收缩压和舒张功能，以及每搏输出量和心输出量。与通常用于啮齿动物导管插入术的开胸方法不同，这种闭胸技术可产生更稳定的生理学和更具生理学相关性的数据。虽然在技术上更具挑战性，并且依赖于操作员的技能才能将导管成功定位在右心室和左心室中，但闭合式胸部入路限制了与开胸手术相关的创伤和出血，并减少了与肺部暴露于大气压力相关的剧烈压力变化。闭合式胸部方法还可以更好地模拟患者进行的心导管插入术，这增强了在临床前研究中使用该技术的相关性。
外科手术是协议的关键步骤。即使使用手术显微镜将导管插入颈静脉或颈动脉（推荐使用），该手术也需要实践和技术技能。通过轻柔、钝的解剖方法仔细解剖脱离周围筋膜的血管将增加插管的成功率，同时将出血风险降至最低。为了尽量减少失血，按顺序插管颈动脉至关重要:1）将导管尖端引入颈动脉;2）轻轻地将缝合线系在包含导管的动脉部分周围;3） 松开固定缝合线，允许导管移动，同时保持轻柔的向上牵引，以尽量减少出血;4）将导管推进至主动脉。通过实时波形监测确定将导管定位在心室中是该协议中最具挑战性的部分。所有导管的电极都应在心室腔内，任何电极都不应接触心室壁。导管的任何不当定位都会导致不规则的 PV 环路，并会对数据采集产生不利影响或妨碍数据采集。识别心室内所有电极所产生的特征压力-体积波形，可以确信适当的导管位置。在切换到 PV 模式和容量采集之前，获得稳定的心室压力波形和稳定的压力大小环路至关重要。正确的心脏生理学和解剖学知识对于该手术的成功至关重要。从心房、三尖瓣区域和右心室在线读取 PV 迹线，将显示导管的进展并有助于实现正确的定位。了解小鼠的正常心率 （400-600 bpm） 以及预期的波形和压力（例如，右心室收缩压 18-25 mm Hg、舒张压 <5 mm Hg;左心室收缩压 60-120 mm Hg40、舒张压 <8 mmHg）至关重要，以便操作员评估观察到的数据的真实性。
数据的质量和可重复性将取决于手术的速度和失血或出血。从麻醉到完成数据采集的过程平均需要 ~30-40 分钟/只小鼠。从插入导管到数据采集的右心导管插入术需要 5-10 分钟，左心导管插入术从插入导管到数据采集还需要 10-15 分钟。在~75%的病例中获得了出版质量的数据。心导管插入术的步骤顺序应在动物之间保持恒定。在该过程中，首先对小鼠进行插管，然后进行右心室导管插入术，最后进行左心室导管插入术。决定按此顺序进行是基于左心导管插入术与右心导管插入术的难度和出血风险更大。可以观察到非特异性的50 Hz噪声记录伪影。使用FIR滤波器，可以在软件上降低该噪声，该滤波器截止频率为50 Hz，截止频率低为0。对于音量通道，创建一个新的通道/过滤器/FIR 过滤器。在数据采集过程中，还可以应用50 Hz的陷波滤波器，以消除电源噪声并消除任何射频干扰。
导管插入术完成得越快，数据质量就越好。根据以往的经验，建议在15分钟内获取数据。导管插入时间的增加增加了动物的生理压力，并增加了由于腔内存在导管而导致心律失常的风险。这些力会降低每搏输出量，并损害波形的再现性和可解释性。此外，导管的尖端很锋利，可能会损坏或刺穿心室。这对右心室尤为重要，右心室的厚度是左 心室厚度的 ~ 1/3。
有创气管切开术和正压机械通气导致小鼠稳定和受控的呼吸，并减少PV环采集的变异性。然而，呼气末正压 （PEEP） 与正常通气形成鲜明对比，正常通气是一种负压现象。正压通气和PEEP共同降低心输出量并降低右心压。因此，虽然需要获取稳定的数据，但机械通气以及麻醉的心脏抑制作用会影响 PV 回路，应被视为一种限制。在短暂记录 PV 回路期间暂时停止机械通气用于消除这种潜在的伪影来源。请注意，通风效率可以通过二氧化碳的二氧化碳监测来确认。
闭胸入路所需的技术技能可能是该技术的局限性。同样，在心室中获得导管的正确、稳定定位也具有挑战性。成功的几率随着操作者的经验以及小鼠的大小和重量而增加。低于20g的小鼠的导尿术极具挑战性。右心室独特的腔室几何形状可能会影响容积测量，应予以考虑。使用的麻醉剂、心率、体温和动物品系可能会影响血流动力学参数，应仔细报告和监测。
总之，在该方案中，右心室和左心室导管插入术在同一只小鼠中进行。根据科学家的具体目标，可以使用双心室手术的相关部分独立进行左心室或右心室导管插入术。然而，所提出的方法是全面评估心脏功能的最佳方法。

根据世界卫生组织 （WHO） 的数据，心脏病是全球男性和女性死亡的主要原因 1,2,3。许多研究侧重于诊断和改善受损的心脏功能4.对于这些应用，高质量和可重复的心脏功能评估至关重要。需要高保真度和可重复的导管数据来评估病因学和治疗反应。例如，心功能评估对于评估药物和其他治疗在心肌梗死临床前模型中的疗效至关重要5.虽然许多心血管研究侧重于左心室功能，但右心室功能也是肺血管疾病患者功能能力和预后的关键决定因素6,7。在晚期心力衰竭患者中，右侧和左侧充盈压持续升高可预测死亡、心血管住院和心脏移植的综合风险8。在主动脉瓣和二尖瓣联合疾病中，术前心肌功能（反映在心脏指数和左心室射血分数等参数中）是长期生存的主要预测指标9。右心室功能是肺动脉高压发病率和死亡率的主要预测因子10,11。因此，右心室功能评估是使用肺动脉高压模型进行综合临床前研究的必要组成部分12,13,14。
左心室和右心室功能通常独立研究。然而，由于左心室和右心室的功能密切相关，因此理想的方法是通过单次测试获得收缩和舒张功能的双心室评估15。例如，右心室与左心室共享室间隔中的斜纤维，左心室构成左心室和右心室收缩功能之间的机械联系之一16,17。这种现象称为收缩期心室相互作用，允许左心室收缩以增强右心室收缩。舒张期的心室相互作用也很重要。在舒张期，一个心室的容积会影响对侧心室的容积，从而改变舒张顺应性和前负荷18,19。在病理条件下，一个心室功能下降或容量负荷受损，可直接或间接损害另一个心室20的功能。由于收缩期心室相互作用，左心室功能的整体下降可能会降低右心室的收缩功能15。在由于左心室收缩功能和舒张末期压力升高引起的心力衰竭患者中，肺动脉压力升高，间接增加右心室后负荷21,22。相反，在重度肺动脉高压患者中，右心室压增高和容量超负荷会对左心产生机械性压迫。左心室的这种D形扁平是由室间隔左移引起的，减少了左心室容积，损害了收缩和舒张功能23,24,25,26,27。因此，在人类疾病临床前模型中，左心室和右心室的评估对于评估整体心脏功能至关重要。
心脏功能也可以通过无创超声心动图、磁共振成像（MRI）和有创导管插入术来评估28,29,30。超声心动图是心血管研究中最常用的成像方式，因为它相对便宜且易于使用31。然而，超声心动图存在一些技术局限性，包括间接测量充盈压力和量化舒张功能的能力有限。此外，超声心动图获得的数据质量在很大程度上取决于操作人员。心脏 MRI 是临床前成像武器库中相对较新的补充，在双心室功能定量评估方面具有巨大潜力。心脏 MRI 的定量是准确的，因为它不像超声心动图32 那样对心室形状做出几何假设。然而，MRI成像平台价格昂贵，而且很少可用。此外，MRI 数据的处理需要物理学家或同等科学家的熟练支持，这在许多临床前实验室中是缺乏的33。同样，在临床前研究中使用显微计算机断层扫描 （MicroCT） 可提供可无创获得的定量高分辨率三维 （3D） 解剖数据，从而允许纵向研究34。然而，MicroCT成像需要注射造影剂，这通常很昂贵。MicroCT成像平台与MRI一样，价格昂贵，并且还需要熟练的技术人员。
相比之下，导管插入术是一种侵入性技术，包括在右心室和/或左心室中引入导管以测量压力和/或体积。进行心导管插入术所需的工具不像超声心动图、CT 或 MRI 那么昂贵。然而，需要对导管插入术和小动物麻醉有相当的技术熟练程度。导管插入术可以直接准确地评估心脏功能28。在该方案中，准入 PV 导管用于评估心脏功能。该技术基于血液和心肌独特的电导特性，可以同时记录心腔内的压力和体积，并实时生成PV环路5,35。简而言之，导管由激发电极和记录电极组成。激励电极在右心室或左心室内产生电场。内部记录电极测量电压变化，这与电阻的变化成正比。推导心室容积基于欧姆定律（电压 = 电流 x 电阻），从中计算电导（即电阻的倒数）。在这种情况下，测得的电导值是血液电导率和肌肉电导率的组合。在电场中，血液是纯电阻性的，而肌肉同时具有电容性和电阻性。肌肉的电容特性会导致测量信号出现时间延迟。跟踪这种延迟，称为"相位"角，报告心脏组织在心脏收缩时侵入野外。该测量值在收缩期最大，在舒张期最低。该特性允许将电导的肌肉成分与血液的电导成分分离，并允许收缩压和舒张压的绝对近似值。压力-容积环提供了一系列血流动力学参数，这些参数不容易通过其他方法测量，例如使用充满液体的导管测量心脏压力的简单逆行导管插入术。压力-容积环测量心室压力，但也提供有关收缩力、弹性、功率、能量和效率的数据。此外，PV 回路提供可靠的定量测量36。因此，通过导管插入术产生的 PV 环评估心脏功能已成为临床前研究的金标准37。此外，临床前技术与人类疾病相关，其中心导管插入术很常见，尽管使用充满液体的导管。然而，啮齿动物的心导管插入术需要无可挑剔的麻醉和出色的技术来防止过度失血、通气不足或体温变化。
在人类患者中，心导管插入术以封闭的胸部结构进行，通过右心室的颈静脉或锁骨下静脉以及左心室的桡动脉或股动脉实现血管通路。由于小鼠体型小，闭胸入路通常具有挑战性。因此，在小鼠中进行的研究通常采用开胸方法。该技术包括打开胸部，从而暴露心脏，并通过穿刺左心室和/或右心室顶点38 促进导管插入。虽然这种方法在技术上不那么具有挑战性且相当可重复，但其主要局限性包括出血和心尖插入导管的其他并发症，以及由于将胸腔打开至大气压而导致心内压显着下降。通气啮齿动物打开胸腔会导致左心室收缩压降低 5-10 毫米汞柱，右心室压力降低 2-5 毫米汞柱39。因此，开发了一种封闭式胸部方法，该方法对心脏的创伤较小，并产生更多生理相关的测量值，这些测量值更容易转化为心脏功能的临床评估。

<table><tbody><tr><td>ADVantage Pressure-Volume System (ADV500)</td><td>Transonic</td><td>FY097B</td><td></td></tr><tr><td>Endozime AW triple plus</td><td>Ruhof</td><td>34521</td><td></td></tr><tr><td>Fiber optic dual Gooseneck</td><td>Volpi Intralux</td><td># 6000-1</td><td></td></tr><tr><td>Forceps</td><td>F.S.T</td><td>11052-10</td><td></td></tr><tr><td>Forceps</td><td>F.S.T</td><td>11251-20</td><td></td></tr><tr><td>Gauze sponges</td><td>Dermacea</td><td>441400</td><td></td></tr><tr><td>Hemostatic clamp</td><td>F.S.T</td><td>13003-10</td><td></td></tr><tr><td>Hemostatic clamp</td><td>F.S.T</td><td>13018-14</td><td></td></tr><tr><td>Heparin sodium</td><td>Sandoz</td><td>023-3086</td><td>100 U/L</td></tr><tr><td>High-fidelity admittance catheter</td><td>Scisence; Transonic</td><td>FTH-1212B-3518</td><td></td></tr><tr><td>Isofluorane</td><td>Baxter</td><td>CA2L9108</td><td></td></tr><tr><td>labScribe v4 software</td><td>iworx</td><td>LS-30PVL</td><td></td></tr><tr><td>Needle (30 gauge)</td><td>BD</td><td>305106</td><td></td></tr><tr><td>sodium chloride injection</td><td>Baxter</td><td>JB1309M</td><td>0.9%(wt/vol)</td></tr><tr><td>Stereo microscope</td><td>Cole-Parmer</td><td>OF-48920-10</td><td></td></tr><tr><td>Surgical suture</td><td>SERAFLEX</td><td>ID158000</td><td>black braided silk, 4.0</td></tr><tr><td>Surgical tape</td><td>3M, Transpore</td><td>SN770</td><td></td></tr><tr><td>Tabletop Single Animal Anesthesia Systems</td><td>Harvard apparatus</td><td>72-6468</td><td></td></tr><tr><td>Tracheotomy canula 1.45 mm diameter</td><td>Harvard apparatus</td><td>72-1410</td><td></td></tr><tr><td>Ventilator, far infrared warming pad for mice and rats PhysioSuite</td><td>Kent scientific corporation</td><td># PS-02</td><td></td></tr></tbody></table>

biventricular assessment of cardiac function and pressure-volume loops by closed-chest catheterization in mice

心脏功能评估对于进行心血管和肺血管临床前研究至关重要。在评估收缩期和舒张期心脏功能时，通过记录心导管插入术期间的压力和容量而产生的压力-容积环（PV 环）至关重要。左心和右心功能密切相关，体现在心室的相互依赖性上。因此，记录同一只动物的双心室功能对于获得完整的心脏功能评估很重要。在该方案中，在小鼠中采用与患者导管插入术一致的方式的封闭式胸腔心导管插入术。虽然具有挑战性，但闭胸策略是一种更具生理学的方法，因为打开胸部会导致前负荷和后负荷发生重大变化，从而产生伪影，最明显的是全身血压下降。虽然高分辨率超声心动图用于评估啮齿动物，但心导管插入术是无价的，尤其是在评估双心室舒张压时。
这里描述的是在同一只动物中执行侵入性、封闭式胸部、顺序左心室和右心室压力容积 （PV） 环的程序。PV 环使用带有鼠标压力-容积导管和压力-容积系统采集的导纳技术进行采集。描述了该过程，从进入右颈静脉和右颈动脉所需的颈部清扫术开始，到导管的插入和定位，最后是数据采集。然后，讨论了确保获得高质量光伏回路所需的标准。最后，简要描述了左心室和右心室PV环路的分析以及可用于量化收缩期和舒张期心室功能的不同血流动力学参数。

在导管插入前30分钟，将导管置于含有肝素化盐水溶液的10mL注射器中（图1A）。将30G针弯曲~90°（图1B，C），并制备直径为1.45mm的气管切开插管（图1C）。
维持生理体温至关重要。鼠标被贴上胶带，并通过鼻锥连接到呼吸器。反馈探头放置在鼠标垫和鼠标背面之间。插入直肠探针以监测动物的体温（图2A）。监测体温（37.1°C）和垫子（40.7°C）温度（图2B）。
插管过程关键步骤的照片如图3A-C所示。成功且畅通无阻的插管导致呼吸频率正常，峰值压力稳定（图2B）。
右心导管插入术的关键步骤的图片，从颈静脉的隔离（图4A-C）到将导管插入颈静脉如图4D所示。图 5 显示了左心导管插入术的关键步骤，包括右颈动脉隔离（图 5 A、B）和导管插入（图 5 C、D）
将导管引入颈静脉并进入右心室。然后稳定右心室压，验证正确定位。所有导管的电极（6 mm 长轴长）都需要在右心室腔内，并且不与心室壁接触。 如图6A 所示的导管的最佳定位产生了最佳的PV环路（即三角形、规则形）。 如图6B 所示的不正确定位（即与心室壁接触）将导致有缺陷的PV环路（即塌陷和不规则的环路）。
将导管引入颈动脉，进入主动脉，然后逆行穿过主动脉瓣进入左心室。左心室压稳定，右心室定位得到验证。所有导管的电极（6 mm 长轴长）应位于左心室腔内，不与心室壁接触。 如图6C 所示的导管的最佳定位产生了最佳的PV环路（即矩形、规则形）。 如图 6D 所示的不当定位（即与心室壁接触）导致有缺陷的 PV 环（即塌陷、非矩形和不规则环）。
左右PV环产生的代表性血流动力学显示心率为410 bpm，心输出量为9,107 μL/min，每搏输出量为24.5 μL。 具体右心室参数显示右心室收缩压为 21.9 mm Hg，右心室舒张末期压力为 1.049 mm Hg，射血分数为 56.1%，dp/dt 最大值为 1,469 mm Hg/s， dp/dt max 为 -1,504 mm Hg/s，舒张末期容积为 38.4 μL，每搏功为 0.068 mJ，压力容积面积为 0.089 mJ，肺动脉弹性系数 （Ea） 为 0.83 mm Hg/μL，Tau 因子为 12.8 ms。具体左心室参数显示左心室收缩压为 77.1 mm Hg，左心室舒张末期压力为 2.33 mm Hg，射血分数为 59.1%，dp/dt max 为 4,695 mm Hg/s，dp/dt max 为 -3,553 mm Hg/s，舒张末期容积为 36.9 μL，每搏功为 0.14 mJ，压力容积面积为 0.22 mJ， 动脉弹性系数 （Ea） 为 5.37 mm Hg/μL，Tau 因子为 15.1 ms（表 1）。
<table border="1" fo:keep-together.within-page="1"><tbody><tr><td>血流动力学参数</td>
			<td></td>
		</tr><tr><td>人力资源 （BPM）</td>
			<td>410.6 ± 23.3</td>
		</tr><tr><td>一氧化碳 （μL/min）</td>
			<td>9107 ± 1016</td>
		</tr><tr><td>SV （微升）</td>
			<td>24.5 ± 2.3</td>
		</tr><tr><td>RV功能</td>
			<td></td>
		</tr><tr><td>RVSP （毫米汞柱）</td>
			<td>21.9 ± 2.15</td>
		</tr><tr><td>RVEDP （毫米汞柱）</td>
			<td>1.042 ± 0.12</td>
		</tr><tr><td>EF （%）</td>
			<td>56.1 ± 4.4</td>
		</tr><tr><td>dP/dt 最大值 （mmHg/s）</td>
			<td>1469 ± 170</td>
		</tr><tr><td>dP/dt 最大值 （- mmHg/s）</td>
			<td>1504 ± 215</td>
		</tr><tr><td>EDV （微升）</td>
			<td>38.4 ± 3.7</td>
		</tr><tr><td>SW （兆焦耳）</td>
			<td>0.068 ± 0.008</td>
		</tr><tr><td>PVA（兆焦耳）</td>
			<td>0.084 ± 0.009</td>
		</tr><tr><td>驿 （mmHg/μL）</td>
			<td>0.83 ± 0.09</td>
		</tr><tr><td>Tau 因子 （ms）</td>
			<td>12.8 ± 0.8</td>
		</tr><tr><td>LV 函数</td>
			<td></td>
		</tr><tr><td>LVSP （毫米汞柱）</td>
			<td>77.1 ± 2.4</td>
		</tr><tr><td>低密度电平 （mmHg）</td>
			<td>2.33 ± 0.17</td>
		</tr><tr><td>EF （%）</td>
			<td>59.1 ± 3.6</td>
		</tr><tr><td>dP/dt 最大值 （mmHg/s）</td>
			<td>4695 ± 355</td>
		</tr><tr><td>dP/dt 最大值 （- mmHg/s）</td>
			<td>3553 ± 373</td>
		</tr><tr><td>EDV （微升）</td>
			<td>36.9 ± 4.8</td>
		</tr><tr><td>SW （兆焦耳）</td>
			<td>0.14 ± 0.013</td>
		</tr><tr><td>PVA（兆焦耳）</td>
			<td>0.22 ± 0.03</td>
		</tr><tr><td>驿 （mmHg/μL）</td>
			<td>5.37 ± 0.9</td>
		</tr><tr><td>Tau 因子 （ms）</td>
			<td>15.07 ± 1.7</td>
		</tr><tr><td colspan="2">CO， 心输出量;Ea， 动脉弹性;EDV，舒张末期容积;心率，心率;LVEDP，左心室舒张末期容积;LVSP，左心室收缩压;PVA， 压力容积面积;RVEDP，右心室舒张末期压;RVSP，右心室收缩压;SV， 每搏输出量;SW， 行程功;Tau 因子，Tau Mirsky。N = 6只小鼠。数值± SEM 表示</td>
		</tr></tbody></table>表1:血流动力学参数表。 在六只小鼠中测量的左心室和右心室血流动力学参数。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/61088/61088fig1.jpg"> 图1:实验准备和设置。 （A） 10 mL 生理盐水/肝素注射器中的导管，（B）、（C） 30 G 针头弯曲至约 90°，（D） 气管切开插管，直径 1.45 mm。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/61088/61088fig1large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/61088/61088fig2.jpg"> 图2:麻醉、 体温控制 。 （A） 用胶带粘住三只爪子的鼠标，通过鼻锥连接到呼吸器，插入反馈和直肠探头。请注意，加热垫位于手术毯下方。（B） 温度监测器控制显示身体（直肠）和垫（反馈）温度和通气参数:呼吸频率（设定 RR）、平均潮气量 （Meas TV）、峰值压力 （PeakPress） 和分钟通气量 （MinVol）。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/61088/61088fig2large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/61088/61088fig3.jpg"> 图 3:插管程序。 （A） 皮肤被拉开并切开。下颌下腺被轻轻地移到一边。将胸锁乳突肌和胸舌骨肌拉开，然后使用轻柔、钝的夹层将镊子穿过气管下方。（B） 将手术丝 （4.0） 穿过气管下方，并在气管的两个软骨环之间向前做一个小切口。插入并结扎气管切开术。（C）将气管切开插管与呼吸机连接，缝合线绑在导管周围。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/61088/61088fig3large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/61088/61088fig4v2.jpg"> 图 4:右心室导管插入术。 （A）、（B）、（C）隔离右颈静脉，然后将一条手术缝合线穿过下方并绑在静脉的颅侧。使用止血钳在头部方向上对该缝合线施加轻柔的牵引力。另外两条缝合线从颈静脉下方的远端穿过。使用止血钳沿尾部方向轻轻拉动最远端的缝合线。在中间缝合线处打了一个松散的潜在结。（D）将导管插入颈静脉，将中间缝合线绑在导管上。（C）和（D）中的图像通过体视显微镜放大。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/61088/61088fig4v2large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/61088/61088fig5.jpg"> 图 5:左心室导管插入术。 （A）、（B）分离右颈动脉，然后将一根手术缝合线穿过颈静脉下方并绑在静脉的颅侧。使用止血钳在头部方向上对该缝合线施加轻柔的牵引力。在颈动脉下方又穿了两条缝合线。使用止血钳沿尾部方向轻轻拉动最远端的缝合线。在中间缝合线中打了一个松散的潜在结。（C）将导管尖端插入颈动脉，然后将中间缝合线绑在导管上以固定。（D） 导管沿着颈动脉向主动脉逆行。（B）、（C）、（D）中的图像通过体视显微镜放大。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/61088/61088fig5large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/61088/61088fig6.jpg"> 图 6:导管定位和由此产生的 PV 回路的示意图。 （A） 右心室中的最佳导管定位。导管的尖端位于心室的中间，与心室壁隔离。由于导管在右心室中的最佳定位（即稳定，三角形）而产生的代表性 PV 环。（B） 右心室导管定位不当。导管的尖端与心室壁接触。由于右心室导管定位不理想（即塌陷、不规则）导致的代表性 PV 环路噪声。（C） 左心室中的最佳导管定位。导管的尖端位于心室的中间，与心室壁隔离。由于导管在左心室中的最佳定位（即稳定、矩形）而产生的代表性 PV 环。（D） 左心室导管定位不当。导管的尖端与心室壁接触。由于左心室导管定位不理想（即塌陷、不规则）导致的代表性 PV 环。应用50 Hz FIR噪声滤波器生成PV环路。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/61088/61088fig6large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>

Watch this Scientific Journal Video about Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice at JoVE.com

Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

这里介绍的是一种评估小鼠双心室心脏功能的方案，通过使用封闭式胸导管插入术从同一动物的右心室和左心室产生压力 - 容积（PV）环。重点是手术和数据采集的技术方面。

小鼠闭胸导管插入术对心功能和压力-容积环的双心室评估

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) ...

biventricular-assessment-cardiac-function-pressure-volume-loops

Nanyang Technological University

Research

JoVE Journal

Medicine

4.1K 次观看.  Queen's University. 这里介绍的是一种评估小鼠双心室心脏功能的方案，通过使用封闭式胸导管插入术从同一动物的右心室和左心室产生压力 - 容积（PV）环。重点是手术和数据采集的技术方面。

视频: Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice

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

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, the RV is significantly affected in pulmonary diseases such as pulmonary artery hypertension (PAH). In addition, the RV is remarkably sensitive to cardiac pathologies, including left ventricular (LV) dysfunction, valvular disease or RV infarction4. To understand the role of RV in the pathogenesis of cardiac diseases, a reliable and noninvasive method to access the RV structurally and functionally is essential.
A noninvasive trans-thoracic echocardiography (TTE) based methodology was established and validated for monitoring dynamic changes in RV structure and function in adult mice. To impose RV stress, we employed a surgical model of pulmonary artery constriction (PAC) and measured the RV response over a 7-day period using a high-frequency ultrasound microimaging system. Sham operated mice were used as controls. Images were acquired in lightly anesthetized mice at baseline (before surgery), day 0 (immediately post-surgery), day 3, and day 7 (post-surgery). Data was analyzed offline using software.
Several acoustic windows (B, M, and Color Doppler modes), which can be consistently obtained in mice, allowed for reliable and reproducible measurement of RV structure (including RV wall thickness, end-diastolic&#160;and end-systolic dimensions), and function (fractional area change, fractional shortening, PA peak velocity, and peak pressure gradient) in normal mice and following PAC.
Using this method, the pressure-gradient resulting from PAC was accurately measured in real-time using Color Doppler mode and was comparable to direct pressure measurements performed with a Millar high-fidelity microtip catheter. Taken together, these data demonstrate that RV measurements obtained from various complimentary views using echocardiography are reliable, reproducible and can provide insights regarding RV structure and function. This method will enable a better understanding of the role of RV cardiac dysfunction.

Right ventricle (RV) dysfunction is critical to the pathogenesis of cardiovascular disease, yet limited methodologies are available for its evaluation. Recent advances in ultrasound imaging provide a noninvasive and accurate option for longitudinal RV study. Herein, we detail a step-by-step echocardiographic method using a murine model of RV pressure overload.

右心室结构和功能的肺动脉缩窄经胸超声小鼠模型的评估

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, ...

Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these strategies is to examine their effects on heart function. There are several techniques to measure in vivo cardiac mechanics (e.g., echocardiography, pressure/volume relations, etc.). Compared to echocardiography, real-time left ventricular (LV) pressure/volume analysis via catheterization is more precise and insightful in assessing LV function. Additionally, LV pressure/volume analysis provides the ability to instantaneously record changes during manipulations of contractility (e.g., &#946;-adrenergic stimulation) and pathological insults (e.g., ischemia/reperfusion injury). In addition to the maximum (+dP/dt) and minimum (-dP/dt) rate of pressure change in the LV, an accurate assessment of LV function via several load-independent indexes (e.g., end systolic pressure volume relationship and preload recruitable stroke work) can be attained. Heart rate has a significant effect on LV contractility such that an increase in the heart rate is the primary mechanism to increase cardiac output (i.e., Bowditch effect). Thus, when comparing hemodynamics between experimental groups, it is necessary to have similar heart rates. Furthermore, a hallmark of many cardiomyopathy models is a decrease in contractile reserve (i.e., decreased Bowditch effect). Consequently, vital information can be obtained by determining the effects of increasing heart rate on contractility. Our and others data has demonstrated that the neuronal nitric oxide synthase (NOS1) knockout mouse has decreased contractility. Here we describe the procedure of measuring LV pressure/volume with increasing heart rates using the NOS1 knockout mouse model.

This article describes the measurement of murine left ventricular function via pressure/volume analysis at different heart rates.

心导​​管在小鼠测量压力体积的关系:调查的影响鲍迪奇

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these ...

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 ...

Quantification of Biventricular Function and Morphology by Cardiac Magnetic Resonance Imaging in Mice with Pulmonary Artery Banding

Right ventricular (RV) function and failure are major determinants of outcome in acquired and congenital heart diseases, including pulmonary hypertension. Assessment of RV function and morphology is complex, partly due to the complex shape of the RV. Currently, cardiac magnetic resonance (CMR) imaging is the golden standard for noninvasive assessment of RV function and morphology. The current protocol describes CMR imaging in a mouse model of RV pressure load induced by pulmonary artery banding (PAB). PAB is performed by placing a 6-0 suture around the pulmonary artery over a 23 G needle. The PAB gradient is determined using echocardiography at 2 and 6 weeks. At 6 weeks, the right and left ventricular morphology and function is assessed by measuring both end-systolic and end-diastolic volumes and mass by ten to eleven cine slices 1 mm thick using a 9.4 T magnetic resonance imaging scanner equipped with a 1,500 mT/m gradient. Representative results show that PAB induces a significant increase in RV pressure load, with significant effects on biventricular morphology and RV function. It is also shown that at 6 weeks of RV pressure load, cardiac output is maintained. Presented here is a reproducible protocol for the quantification of biventricular morphology and function in a mouse model of RV pressure load and may serve as a method for experiments exploring determinants of RV remodeling and dysfunction.

<meta charset="utf8"></head><body>通过心脏磁共振成像定量肺动脉束带小鼠的双心室功能和形态

To understand the pathophysiology of right ventricular (RV) adaptation to abnormal loading, experimental models are crucial. However, assessment of RV dimensions and function is complex and challenging. This protocol provides a method to perform cardiac magnetic resonance imaging (CMR) as a noninvasive benchmark procedure in mice subjected to RV pressure load.

通过心脏磁共振成像定量肺动脉束带小鼠的双心室功能和形态

Right ventricular (RV) function and failure are major determinants of outcome in acquired and congenital heart diseases, including pulmonary hypertension. ...

Cardiac Response to &#946;-Adrenergic Stimulation Determined by Pressure-Volume Loop Analysis

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of specific treatments on the heart. Due to the feasibility of genetic manipulations the mouse has become the most common mammalian animal model to study cardiac function and to search for new potential therapeutic targets. Here we describe a protocol to determine cardiac function&#160;in vivo using pressure-volume loop measurements and analysis during basal conditions and under &#946;-adrenergic stimulation by intravenous infusion of increasing concentrations of isoproterenol. We provide a refined protocol including ventilation support taking into account the positive end-expiratory pressure to ameliorate negative effects during open-chest measurements, and potent analgesia (Buprenorphine) to avoid uncontrollable myocardial stress evoked by pain during the procedure. All together the detailed description of the procedure and discussion about possible pitfalls enables highly standardized and reproducible pressure-volume loop analysis, reducing the exclusion of animals from the experimental cohort by preventing possible methodological bias.

Here we describe a cardiac pressure-volume loop analysis under increasing doses of intravenously infused isoproterenol to determine the intrinsic cardiac function and the &#946;-adrenergic reserve in mice. We use a modified open-chest approach for the pressure-volume loop measurements, in which we include ventilation with positive end-expiratory pressure.

通过压力-体积环路分析确定心脏对β肾上腺素能刺激的反应

Determination of the cardiac function is a robust endpoint analysis in animal models of cardiovascular diseases in order to characterize effects of ...

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular systolic and diastolic function. Measures of ventricular contractility and compliance are obtained through examination of cardiac response to changes in afterload and preload. These techniques were originally developed nearly three decades ago to measure cardiac function in large mammals and humans. The application of these analyses to small mammals, such as mice, has been accomplished through the optimization of microsurgical techniques and creation of conductance catheters. Conductance catheters allow for estimation of the blood pool by exploiting the relationship between electrical conductance and volume. When properly performed, these techniques allow for testing of cardiac function in genetic mutant mouse models or in drug treatment studies. The accuracy and precision of these studies are dependent on careful attention to the calibration of instruments, systematic conduct of hemodynamic measurements and data analyses. We will review the methods of conducting pressure-volume loop experiments using a conductance catheter in mice.

Cardiac pressure-volume loop analysis is the most comprehensive way to measure cardiac function in the intact heart. We describe a technique to perform and analyze cardiac pressure volume loops, using conductance catheters.

心脏压力容量环分析小鼠使用电导导管

Cardiac pressure-volume loop analysis is the &#8220;gold-standard&#8221; in the assessment of load-dependent and load-independent measures of ventricular ...

生物学

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

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

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

猪模型中闭合胸部双心室压力-体积循环记录与导管

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

小鼠闭胸导管插入术对心功能和压力-容积环的双心室评估

摘要

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通过心脏磁共振成像定量肺动脉束带小鼠的双心室功能和形态

通过心脏磁共振成像定量肺动脉束带小鼠的双心室功能和形态

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猪模型中闭合胸部双心室压力-体积循环记录与导管

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摘要

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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

右心室结构和功能的肺动脉缩窄经胸超声小鼠模型的评估

心导​​管在小鼠测量压力体积的关系:调查的影响鲍迪奇

小鼠急性心肌梗死的实时压力容积分析

通过心脏磁共振成像定量肺动脉束带小鼠的双心室功能和形态

通过心脏磁共振成像定量肺动脉束带小鼠的双心室功能和形态

通过压力-体积环路分析确定心脏对β肾上腺素能刺激的反应

心脏压力容量环分析小鼠使用电导导管

猪模型中闭合胸部双心室压力-体积循环记录与导管

心导管在小鼠测量压力体积的关系:调查的影响鲍迪奇