本次工作得到了四川省重大研发专项（2022YFS043）和成都中医药大学青年基金会发展人才专项（QJJJ2022029）的支持。

该动物实验方案经成都中医药大学实验动物福利伦理委员会审核通过（备案号：2023-04）。本研究使用雄性 Sprague Dawley （SD） 大鼠（280 ± 20 g，8-10 周龄）。老鼠被关在动物室里，可以自由饮水和进食。
1.溶液制备
<ol><li>准备 0.9% NaCl 溶液，用于保持工作区域充分湿润。</li>
	<li>要制备 20% 高渗 NaCl 溶液，将 2 g NaCl 溶解在 10 mL 双蒸水 （ddH2O） 中。为了确定心肌的平行电导率，有必要改变脑室内液体的电导率。</li>
	<li>制备1%的酶活性粉末洗涤剂溶液。在实验完成时使用它，将压力容积导管浸入溶液中1-2小时。</li>
	<li>通过将 10 mg 阿魏酸溶解在 20 mL ddH2O 中来制备 FA 溶液，通过 0.22 μm 膜过滤溶液。向大鼠注射1mL / kg阿魏酸溶液。</li>
</ol>2.传感器的准备
<ol><li>在实验开始前，将压力体积传感器浸入37°C的0.9%NaCl溶液中约30-60分钟，这有助于实验数据的稳定性。</li>
	<li>连接实验设备。测量压力-容积回路的系统由一根压力-容积导管、两个控制单元、一个记录单元和计算机运行软件组成。软件中的压力-体积回路模块将提供参考实验程序。</li>
	<li>按 下“开始 ”按钮，软件将自动记录来自压力体积传感器的监测数据。</li>
	<li>使用 Miro-Tip 压力体积 （MPVS） 软件校准压力和电导率。</li>
</ol>3.实验前大鼠制备
<ol><li>通过肌肉注射给大鼠氯胺酮（50mg / kg）和芬太尼（0.25mg / kg）5。</li>
	<li>捏住大鼠的脚趾，通过没有反射来验证麻醉深度。情绪会影响大鼠的生理状态，疼痛会导致心脏功能的改变16.使用小动物剃须刀和脱毛膏去除手术部位的毛发。使用碘磷和 75% 酒精擦拭皮肤以保持无菌。</li>
	<li>将完全麻醉的大鼠固定在等温加热板上，背部与加热板接触。</li>
	<li>将涂有凡士林的温度探头插入大鼠的直肠中。通过调节加热板将大鼠体温保持在37°C±0.5。 注意：在实验过程中必须保持气道畅通。</li>
</ol>4. 将导管插入右颈动脉
<ol><li>纵向切开大鼠颈部正中线右侧的皮肤。做一个 4 厘米的切口，用镊子分离肌肉和结缔组织。位于气管右侧的颈动脉是可见的。大鼠的右颈动脉呈暗红色，脉动强烈，并有一条与之平行的白色迷走神经。</li>
	<li>使用镊子将颈动脉与其他组织和神经分开。在干净的颈动脉下方放置三条 5-0 手术线。将无菌的0.9%氯化钠溶液滴入手术区域，以保持颈动脉的湿润。</li>
	<li>切开左锁骨上方的皮肤，剥离颈静脉周围的组织。然后，在左颈静脉下方放置一个 5-0 手术线。</li>
	<li>使用动脉夹暂停近端的血流，使用微型剪刀剪断血管中血流停止的部分。伤口横截面出现少量血液是正常的。如果血液快速间歇性地流出血管，请抬起近端手术管并再次使用动脉钳。</li>
	<li>将导管从横截面沿颈动脉深入左心室。确保进入左心室后的最低收缩压值接近 0 mmHg。</li>
	<li>为了获得合理的压力-容积关系，稍微调整心室中的压力-容积导管。为防止大量失血和导管因心跳而改变位置，请结扎手术管路的近端。 注意：在此过程中，大鼠的体温、麻醉水平、压力信号和电导信号应保持稳定。大鼠的呼吸道应保持畅通。</li>
</ol>5.药物注射和电导率校准
<ol><li>保持压力容积导管在心室腔室中的位置，数据稳定后，结扎颈静脉远端的手术管线结扎并缓慢注射至1mL / kg阿魏酸溶液。观察5-10分钟。</li>
	<li>从左颈静脉注射 50 μL 20% NaCl 溶液以去除心肌产生的平行电导。平行电导的体积范围约为 130-280 μL5。以 2 分钟的间隔重复此操作 3 次。</li>
	<li>在大鼠进行心室压力和容量测试后，使用采血针从大鼠腹主动脉抽血。将收集的血液放入肝素钠收集管中，上下倒置 2 次以防止血液凝固。通过左颈静脉注射120mg / kg戊巴比妥钠对实验大鼠实施安乐死。</li>
	<li>使用大鼠容量校准管将测得的电导转换为实际血容量。将血液与肝素钠混合的血液依次放入校准管的孔中，导管检测不同孔中血液的电导值并将其记录在压力-容积监测模块中。</li>
</ol>6. 数据分析
<ol><li>通过将已知体积血液的测量电导率值添加到指定位置，软件会自动绘制曲线并推断血液的电导率。使用至少三组血液电导率值来推断被测大鼠的血液电导率。血液电导率是个体化的。对于测试下的每只大鼠，分别执行此程序。</li>
	<li>高渗校准：通过将三次高渗盐水注射获得的数据添加到指定位置，软件计算平行电导平均值并自动校准实验数据。</li>
	<li>利用血压和电导值稳定的区域分析大鼠的左心室功能。</li>
	<li>点击 “分析 ”，软件会根据所选区域自动计算各种参数，包括EF（左心室射血分数）、SW（卒中功）和CO（心输出量）等。</li>
</ol>

使用压力-体积电导技术监测大鼠的心脏功能

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作者声明，该研究是在没有任何可被解释为潜在利益冲突的商业或财务关系的情况下进行的。

对于不同的心脏功能状态，必须采用合理的给药策略。压力-容积电导导管技术是研究左心室功能最直观的方法5.这种方法可以从整体角度研究药物对心脏功能的影响。我们详细描述了实验的各个阶段。这将为心脏功能的研究提供一些便利。
压力容积电导率导管技术是最全面、最严格的方法。在一次实验中可以获得多达30个指标的信息，包括绝对值（压力和体积）和相对值（EF），甚至还有一些药物代谢信息。
在整个实验过程中，大鼠的体温保持在37°C±0.55。在实验5期间，应尽量减少大鼠的失血量。在实验17期间应注意大鼠的血容量。
压力-容积传导导管技术允许实时检测心室的状态 18.该技术对于研究单一药物或药物组合对心脏的影响非常有帮助。电导导管将直接测量左心室的压力和电导。这与被测大鼠的体温和麻醉程度密切相关。在该实验中，注射阿魏酸溶液后，压力-容积环清楚地证明了左心室功能的变化，包括收缩末期压和收缩末期容积的降低（图2A）。大鼠左心室射血分数显著升高，峰值为89.87%（图2B）。大鼠左心室收缩末压显著降低，最小值为55.44μL。这与先前报道的阿魏酸在降低血压方面的药理作用一致11。
在食品和药用植物中发现的某些天然化合物有助于维持健康。阿魏酸是一种广泛存在于植物中的酚类化合物，包括川芥和当归19，是各种中药的重要活性成分。目前的研究表明，阿魏酸具有多种生物活性，包括抗炎、抗纤维化和抗凋亡作用11。有必要研究这种食物中现成的天然产物对循环系统中心脏功能的影响，尽管研究表明它对心脏形态结构有积极影响12,20。
压力容积导管可放置在实验动物的心室腔内，直接获得心室压力和电导。盐水校准和比色皿校准用于获得真实的心室容积。该实验允许获得连续的压力-容积循环，这将直观地反映心室功能的变化。使用压力容积导管进入心室有两种方法，包括开胸和闭胸。在开胸条件下，更容易控制压力容积导管在心室腔中的位置。在闭胸条件下测量心室功能不需要动物辅助呼吸，对动物的伤害较小，成功率更高。此外，在闭胸条件下观察压力容积环，以确定压力容积导管是否在心室腔内。如果该导管被心肌压缩，压力容积环将出现异常峰值。
心脏是将血液泵送到全身的重要器官。需要一种更合理的方法来评估心脏功能，包括负荷前后以及心脏本身的状态21.压力-容积环用于实时描述整个心动周期中心室压力和容积的变化。该协议描述了使用微型传感器测量左心室功能的完整方法。改变实验方案中的微传感器模型可以测量不同动物的心脏功能，例如猪、小鼠等4,8,22。使用压力容积电导导管可以实时观察药物对左心室压力和容积的影响，以及对实验对象循环系统的整体影响。这种技术有助于最大限度地减少药物对心脏的潜在负面影响。

心血管疾病是世界上死亡率最高的国家 1.其病因包括冠状动脉狭窄（心肌缺血）、冠状动脉阻塞（心肌梗死）和缺血再灌注损伤2。由于心脏处于恒定的收缩期和舒张期，它是身体最需要能量的部位之一。因此，当冠状动脉难以维持足够的能量和氧气时，心脏功能不可避免地下降，从而对其他器官产生负面影响3,4。心脏是循环系统中的动力源，需要理性评估心脏功能。
通过心室压力和容量关系评估心脏功能被认为是一种综合方法5。在整个心动周期中，心室压力和容积的实时变化构成了压力-容积环。心室压力-容积环可以根据心室的不同阶段和能量对心脏功能和储备能力进行定量分析。正常心室收缩末期容积小，搏动功好，效率高5,6,7。
压力容积传导导管技术是一种检测左心室状态的侵入性方法。它可用于获得连续的实时压力-体积回路8。 压力容积电导率导管是强大的工具，良好的处理程序对于可重复和可靠的结果至关重要，包括在生理盐水校准期间对心肌平行电导率进行 体内 分析，以及在比色皿校准中对血液电导率进行 体外 测量3。
阿魏酸（FA）是一种酚酸，广泛分布于植物界，如燕麦和女贞子9,10。阿魏酸具有降低血压和心律失常的药理作用。FA是一种具有多种功能的生物活性天然产物。FA能抵抗氧化损伤，减少炎症反应，抑制血小板聚集，预防冠心病和动脉粥样硬化11。然而，大多数关于阿魏酸的研究都集中在心脏的一个方面，很少评估阿魏酸在循环系统中的作用12,13,14,15。在这里，我们描述了一种异氟醚麻醉联合氯胺酮 （50 mg/kg） 的闭胸方法，重点是颈静脉注射过程中对阿魏酸溶液的心脏反应。
我们将描述在闭胸条件下使用该工具的完整程序，包括溶液制备、换能器制备、实验前大鼠制备、导管插入右颈动脉和数据分析。实验的持续时间通常小于4小时，由不同的实验方案决定。在单个实验中，我们可以获得详细的心脏信息，例如左心室压力、容量和心率。

<table><tbody><tr><td>1 mL syringe</td><td>Sartorius AG, Germany</td><td>-</td><td></td></tr><tr><td>Animal temperature maintainer</td><td>Rayward Life Technology Co., Ltd</td><td>69020</td><td></td></tr><tr><td>Dual Bio Amp</td><td>Millar, Inc., USA</td><td>DA-100</td><td></td></tr><tr><td>Enzyme-Active Powdered Detergent</td><td>Alconox Inc., USA</td><td>1104</td><td></td></tr><tr><td>Ferulic acid</td><td>&amp;nbsp;Macklin Biochemical Co., Ltd,Shanghai, China</td><td>F900027</td><td></td></tr><tr><td>Mikro-Tip Catheter Transducers, SPR-838NR</td><td>Millar, Inc., USA</td><td>SPR-838NR</td><td></td></tr><tr><td>Millar Miro-Tip Pressure Volume (MPVS) Ultra</td><td>Millar, Inc., USA</td><td>SPR-869</td><td></td></tr><tr><td>Pet electric clippers</td><td>Jinyun County New Concept Home Supplies Co., Ltd.</td><td>&amp;nbsp;-</td><td></td></tr><tr><td>Power Lab 8 / 35</td><td>Millar, Inc., USA</td><td>PL3508</td><td></td></tr><tr><td>Sodium Chloride, NaCl</td><td>&amp;nbsp;Kelong Chemical Reagent, Chengdu, China</td><td>KX829463</td><td></td></tr><tr><td>Veet hair removal cream</td><td>Shanghai Songqi E-commerce Co., Ltd.</td><td>3226470</td><td></td></tr></tbody></table>

real-time detection of ferulic acid effects on rat left ventricle using pressure-volume conductivity catheter

心脏功能下降会对其他器官产生负面影响。左心室压力-容积关系被认为是评估心脏功能的有效方法。心脏功能的实时监测对于药物评估非常重要。在闭胸条件下，微型换能器是压力容积导管的重要组成部分，通过右颈动脉进入大鼠的左心室。该设备以压力-容积环的形式可视化实验过程中心脏功能的变化。通过将50μL20%氯化钠溶液注射到大鼠的左颈静脉中来改变血液的电导率来计算心室的实际体积。通过使用压力 - 体积电导导管测量已知体积中血液的电导率来计算大鼠心室腔的实际体积。该协议允许持续观察药物对心脏的影响，并将促进在心血管疾病中使用特殊种族药物的基本原理。

每个测试 （n = 3） 都基于压力容积电导率导管进入左心室。当导管从颈动脉进入左心室时，信号会发生显著变化，例如压力范围明显增加（图 1）。通过绘制 Y 轴上的体积 （μL） 和 X 轴上的压力 （mmHg） 来完成压力-体积关系的图形分析。大鼠左心室压在10-105 mmHg以内，体积电导值在65-115 μL以内。
完整的心动周期由逆时针压力-容积环形成（图2）。在大鼠施用阿魏酸后，观察到心脏功能的显着变化（图3）。大鼠左心室压在0-85 mmHg之间，体积电导值在30-100 μL之间。
如 图4所示，当将高渗盐水注射到大鼠颈静脉中时，左心室压力-容积环发生变化。由于直接测量心室内的压力和电导率信号，通过左颈静脉注射高渗盐水可导致电导率值增加。通过多次测量电导率值的变化，可以消除来自心肌的干扰。
压力体积电导用于比色皿校准（图5）。这是将测得的电导值转换为体积值。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/65858/65858fig01.jpg"> 图 1：由压力-容积电导导管在颈动脉和心室中产生的不同压力-容积环。 （A）动脉和心室之间的压力和电导率存在显着差异。（B） 将微型传感器插入心室可以形成压力-容积回路。 <a href="https://www.jove.com/files/ftp_upload/65858/65858fig01large.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/65858/65858fig02.jpg"> 图 2：压力-体积回路。 压力-容积环包括四个阶段：舒张期、等容收缩期、收缩期和等容松弛期。压力-容积环的面积代表一次心脏收缩产生的功。从舒张末期容积 （EDV） 中减去收缩末期容积 （ESV） 得到心室输出量。 <a href="https://www.jove.com/files/ftp_upload/65858/65858fig02large.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/65858/65858fig03.jpg"> 图3：注射阿魏酸溶液后大鼠左心室功能受到影响。 （A） 左心室压力-容积环受到影响。（B） 射血分数 （EF） 表示每搏输出量相对于心室舒张末期容积的百分比：左心室射血分数随心跳计数的变化。（C） 左心室收缩末期容积随心跳次数的增加而变化。（D） 左心室舒张末压-容积关系时间常数随心率增加而变化。 <a href="https://www.jove.com/files/ftp_upload/65858/65858fig03large.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/65858/65858fig04.jpg"> 图4：将20%NaCl溶液注射到静脉后大鼠左心室的压力和电导变化。 （A）电导率发生变化的分析数据。（B） 由于电导率增加，压力体积环向右移动。 <a href="https://www.jove.com/files/ftp_upload/65858/65858fig04large.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/65858/65858fig05.jpg"> 图 5：压力体积电导导管用于测量充满大鼠血液的已知体积比色皿的电导率。 （A）不同体积的电导率。（B） 通过压力-体积电导率导管测量的电导率具有良好的相关性。 <a href="https://www.jove.com/files/ftp_upload/65858/65858fig05large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>

Watch this Scientific Journal Video about Author Spotlight: Advantages of Pressure-Volume Loop Measurement Method in Cardiovascular Research at JoVE.com

作者聚焦：压力-体积环测量方法在心血管研究中的优势

该协议描述了一种使用压力 - 体积电导技术测量左心室压力和体积的方法。这种方法可以连续实时监测药物对心脏的影响。

使用压力-容积电导导管实时检测阿魏酸对大鼠左心室的影响

Decreased cardiac function can have a negative impact on other organs. The left ventricular pressure-volume relationship is considered to be a valid ...

麻醉是动物实验中不可避免的问题。在本实验中，不同程度的麻醉对实验结果有显著影响。与开胸法相比，这种压力-容积环测量方法更易于学习，包括更少的实验工具和更少的实验人员学习时间。我们的实验室将研究中医对心血管疾病的影响，探索其对心脏健康的广泛但尚未完全了解的影响。

real-time-detection-ferulic-acid-effects-on-rat-left-ventricle-using

Nanyang Technological University

Research

JoVE Journal

Medicine

Real-Time Detection of Ferulic Acid Effects on Rat Left Ventricle Using Pressure-Volume Conductivity Catheter

403 次观看.  Chengdu University of Traditional Chinese Medicine. 麻醉是动物实验中不可避免的问题。在本实验中，不同程度的麻醉对实验结果有显著影响。与开胸法相比，这种压力-容积环测量方法更易于学习，包括更少的实验工具和更少的实验人员学习时间。我们的实验室将研究中医对心血管疾病的影响，探索其对心脏健康的广泛但尚未完全了解的影响。

视频: 作者聚焦：压力-体积环测量方法在心血管研究中的优势

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.
Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.

Heart failure is the leading cause of hospitalization and a major cause of mortality. A model of permanent ligation of the left anterior descending coronary artery in mice is applied to investigate ventricular remodelling and cardiac dysfunction post-myocardial infarction. The technique of invasive hemodynamic measurements in mice is presented.

左冠状动脉前降支的小鼠结扎:对心肌梗死后重塑和心衰模型

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It ...

科研

医学

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 ...

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. ...

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily and highly reproducible MI induction procedure is required to obtain further insight and better understanding of the underlying pathological changes. This procedure can also be used to evaluate the effects or potency of new and promising treatments (as drugs or interventions) in acute MI, subsequent remodeling and heart failure (HF). After intubation and pre-operative preparation of the animal, an anesthetic protocol with isoflurane was performed, and the surgical procedure was conducted&#160;quickly. Using a minimally invasive approach, the left anterior descending artery (LAD) was located and occluded by a ligature. The occlusion can be performed acutely for subsequent reperfusion (ischemia/reperfusion injury). Alternatively, the vessel can be ligated permanently to investigate the development of chronic MI, remodeling or HF. Despite common pitfalls, the drop-out rates are minimal. Various treatments such as remote ischemic conditioning can be examined for their cardioprotective potential pre-, peri- and post-operatively. The post-operative recovery was quick as the anesthesia was precisely controlled and the duration of the operation was short. Post-operative analgesia was administered for three days. The minimally invasive procedure reduces the risk of infection and inflammation. Furthermore, it facilitates rapid recovery. The &#8220;working heart&#8221; measurements were performed ex vivo and enabled precise control of preload, afterload and flow. This procedure requires specific equipment and training for adequate performance. This manuscript provides a detailed step-by-step introduction for conducting these measurements.

This article presents an efficient method to perform myocardial ischemia and subsequent chronic reperfusion in rats using a minimally invasive approach. In addition, left ventricular hemodynamic function of rats is assessed by echocardiography and isolated working heart methods.&#160;

诱导大鼠心肌梗死的半微创方法及独立工作心脏系统对心脏功能的评估

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily ...

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

Assessment of cardiac function is essential to conduct cardiovascular and pulmonary-vascular preclinical research. Pressure-volume loops (PV loops) generated by recording both pressure and volume during cardiac catheterization are vital when assessing both systolic and diastolic cardiac function. Left and right heart function are closely related, reflected in ventricular interdependence. Thus, recording biventricular function in the same animal is important to get a complete assessment of cardiac function. In this protocol, a closed chest approach to cardiac catheterization consistent with the way catheterization is performed in patients is adopted in mice. While challenging, the closed chest strategy is a more physiological approach, because opening the chest results in major changes in preload and afterload that create artifacts, most notably a fall in systemic blood pressure. While high-resolution echocardiography is used to assess rodents, cardiac catheterization is invaluable, particularly when assessing diastolic pressures in both ventricles.
Described here is a procedure to perform invasive, closed chest, sequential left and right ventricular pressure-volume (PV) loops in the same animal. PV loops are acquired using&#160;admittance technology with a mouse pressure-volume catheter and pressure-volume system acquisition. The procedure is described, beginning with the neck dissection, which is required to access the right jugular vein and the right carotid artery, to the insertion and positioning of the catheter, and finally the data acquisition. Then, the criteria required to ensure the acquisition of high-quality PV loops are discussed. Finally, the analysis of the left and right ventricular PV loops and the different hemodynamic parameters available to quantify systolic and diastolic ventricular function are briefly described.

Presented here is a protocol to assess biventricular heart function in mice by generating pressure-volume (PV) loops from the right and left ventricle in the same animal using closed chest catheterization. The focus is on the technical aspect of surgery and data acquisition.

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) ...

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

Measuring Pressure Volume Loops in the Mouse

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the mouse provides great potential to explore cardiac function at the molecular level. The mouse&#39;s small size does present some challenges in regards to performing detailed cardiac phenotyping. Miniaturization and other advancements in technology have made many methods of cardiac assessment possible in the mouse. Of these, the simultaneous collection of pressure and volume data provides a detailed picture of cardiac function that is not available through any other modality. Here a detailed procedure for the collection of pressure-volume loop data is described. Included is a discussion of the principles underlying the measurements and the potential sources of error. Anesthetic management and surgical approaches are discussed in great detail as they are both critical to obtaining high quality hemodynamic measurements. The principles of hemodynamic protocol development and relevant aspects of data analysis are also addressed.

This manuscript describes a detailed protocol for the collection of pressure-volume data from the mouse.

测量压力容量环中的鼠标

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the ...

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography

A reliable noninvasive approach for functional assessment of the donor heart during normothermic ex situ heart perfusion (NESP) is lacking. We herein describe a protocol for ex situ assessment of myocardial performance using the epicardial echocardiography and conductance catheter method.

非原位灌注期间供体心脏的功能评估:来自压力-容量环和表面超声心动图的见解

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the ...

使用压力-容积电导导管实时检测阿魏酸对大鼠左心室的影响

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左冠状动脉前降支的小鼠结扎:对心肌梗死后重塑和心衰模型

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

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

诱导大鼠心肌梗死的半微创方法及独立工作心脏系统对心脏功能的评估

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

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

测量压力容量环中的鼠标

非原位灌注期间供体心脏的功能评估:来自压力-容量环和表面超声心动图的见解

使用压力-容积电导导管实时检测阿魏酸对大鼠左心室的影响

副本

摘要

探索更多视频

此视频中的章节

左冠状动脉前降支的小鼠结扎:对心肌梗死后重塑和心衰模型

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

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

诱导大鼠心肌梗死的半微创方法及独立工作心脏系统对心脏功能的评估

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

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

测量压力容量环中的鼠标

非原位灌注期间供体心脏的功能评估:来自压力-容量环和表面超声心动图的见解

心导管在小鼠测量压力体积的关系:调查的影响鲍迪奇