Name: a rat model of pressure overload induced moderate remodeling and systolic dysfunction as opposed to overt systolic heart failure
Uploaded: 2020-04-30T14:30:00
Description: Watch this Scientific Journal Video about A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure at JoVE.com

NIH 向 P.D 授予 HL070241。

这里描述的所有方法和程序都已获得杜兰大学医学院机构动物护理和使用委员会（IACUC）的批准。
1. 创建 AAB 模型的工具和工具
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	<li>McMurray, J. J., Petrie, M. C., Murdoch, D. R., Davie, A. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+epidemiology+of+heart+failure:+public+and+private+health+burden.">Clinical epidemiology of heart failure: public and private health burden.</a> European Heart Journal. 19 (Suppl P), P9-P16 (1998).</li><li>Berk, B. C., Fujiwara, K., Lehoux, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ECM+remodeling+in+hypertensive+heart+disease.">ECM remodeling in hypertensive heart disease.</a> Journal of Clinical Investigation. 117 (3), 568-575 (2007).</li><li>Frey, N., Olson, E. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+hypertrophy:+the+good,+the+bad,+and+the+ugly.">Cardiac hypertrophy: the good, the bad, and the ugly.</a> Annual Review of Physiology. 65, 45-79 (2003).</li><li>Hill, J. A., Olson, E. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+plasticity.">Cardiac plasticity.</a> New England Journal of Medicine. 358 (13), 1370-1380 (2008).</li><li>Kehat, I., Molkentin, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+pathways+underlying+cardiac+remodeling+during+pathophysiological+stimulation.">Molecular pathways underlying cardiac remodeling during pathophysiological stimulation.</a> Circulation. 122 (25), 2727-2735 (2010).</li><li>Rothermel, B. A., Hill, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autophagy+in+load-induced+heart+disease.">Autophagy in load-induced heart disease.</a> Circulation Research. 103 (12), 1363-1369 (2008).</li><li>Barrick, C. 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=Parent-of-origin+effects+on+cardiac+response+to+pressure+overload+in+mice.">Parent-of-origin effects on cardiac response to pressure overload in mice.</a> American Journal of Physiology-Heart and Circulatory Physiology. 297 (3), H1003-H1009 (2009).</li><li>Barrick, C. J., Rojas, M., Schoonhoven, R., Smyth, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+response+to+pressure+overload+in+129S1/SvImJ+and+C57BL/6J+mice:+temporal-+and+background-dependent+development+of+concentric+left+ventricular+hypertrophy.">Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy.</a> American Journal of Physiology-Heart and Circulatory Physiology. 292 (5), H2119-H2130 (2007).</li><li>Lygate, C. A., 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=Serial+high+resolution+3D-MRI+after+aortic+banding+in+mice:+band+internalization+is+a+source+of+variability+in+the+hypertrophic+response.">Serial high resolution 3D-MRI after aortic banding in mice: band internalization is a source of variability in the hypertrophic response.</a> Basic Research in Cardiology. 101 (1), 8-16 (2006).</li><li>Chaanine, A. H., Hajjar, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+the+Differential+Progression+of+Left+Ventricular+Remodeling+in+a+Rat+Model+of+Pressure+Overload+Induced+Heart+Failure.+Does+Clip+Size+Matter?.">Characterization of the Differential Progression of Left Ventricular Remodeling in a Rat Model of Pressure Overload Induced Heart Failure. Does Clip Size Matter?.</a> Methods in Molecular Biology (Clifton, N.J.). 1816, 195-206 (2018).</li><li>Chaanine, A. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mitochondrial+Integrity+and+Function+in+the+Progression+of+Early+Pressure+Overload-Induced+Left+Ventricular+Remodeling.">Mitochondrial Integrity and Function in the Progression of Early Pressure Overload-Induced Left Ventricular Remodeling.</a> Journal of the American Heart Association. 6 (6), (2017).</li><li>Chaanine, A. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Potential+role+of+BNIP3+in+cardiac+remodeling,+myocardial+stiffness,+and+endoplasmic+reticulum:+mitochondrial+calcium+homeostasis+in+diastolic+and+systolic+heart+failure.">Potential role of BNIP3 in cardiac remodeling, myocardial stiffness, and endoplasmic reticulum: mitochondrial calcium homeostasis in diastolic and systolic heart failure.</a> Circulation: Heart Failure. 6 (3), 572-583 (2013).</li><li>Takagawa, 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=Myocardial+infarct+size+measurement+in+the+mouse+chronic+infarction+model:+comparison+of+area-+and+length-based+approaches.">Myocardial infarct size measurement in the mouse chronic infarction model: comparison of area- and length-based approaches.</a> Journal of Applied Physiology (Bethesda, Md. : 1985). 102 (6), 2104-2111 (2007).</li><li>Vietta, G. 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=Early+use+of+cardiac+troponin-I+and+echocardiography+imaging+for+prediction+of+myocardial+infarction+size+in+Wistar+rats.">Early use of cardiac troponin-I and echocardiography imaging for prediction of myocardial infarction size in Wistar rats.</a> Life Sciences. 93 (4), 139-144 (2013).</li><li>Frangogiannis, N. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+inflammatory+response+in+myocardial+injury,+repair,+and+remodelling.">The inflammatory response in myocardial injury, repair, and remodelling.</a> Nature Reviews. Cardiology. 11 (5), 255-265 (2014).</li><li>Doggrell, S. A., Brown, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+models+of+hypertension,+cardiac+hypertrophy+and+failure.">Rat models of hypertension, cardiac hypertrophy and failure.</a> Cardiovascular Research. 39 (1), 89-105 (1998).</li></ol>

在大鼠中与AAB相关的PO之后，LV通过增加LV壁厚（称为同心LVH）进行同心重塑，作为补偿机制，以抵消LV壁应力的增加。在 AAB 之后的第一周，LV 壁厚度的增加变得明显，并在 AAB 后 2-3 周内达到其最大厚度。在此期间，不自适应信号转导通路的激活导致LV逐渐扩大，LV体积增加，这个过程称为偏心肥大或重塑。预计大鼠的HF表型在大多数动物中出现AAB后8周左右，其中很少在AAB之后的第12周出现HF。根据...

心力衰竭（HF）是一种普遍的疾病，与高发病率和死亡率1相关。由上升或横向主动脉带带产生的HF的啮齿动物压载过载（PO）模型通常用于探索导致HF的分子机制和测试HF中潜在的新治疗靶点。他们还模仿人类HF继发到长期全身性高血压或严重主动脉狭窄的变化。PO 之后，左心室 （LV） 壁的厚度逐渐增加，这个过程称为同心 LV 肥大 （LVH），以补偿和适应 LV 壁应力的增加。然而，这与一些不适应信号通路的激活有关，这导致钙循环和平衡、代谢和细胞外基质重塑和基因表达变化的紊乱的发生，以及增强的凋亡和自噬2,2，3，4，5，6。3,4,5,6这些分子变化构成心肌重塑启动和传播的触发因素，并转化为补偿性HF表型。
尽管使用近亲啮齿动物菌株和标准化的夹大小和手术技术，有巨大的阴极变异在LV室结构和功能在主动脉带模型77，8，9。8,9大鼠PO后遇到的比世变异性，斯普拉格-道利菌株，被描述在其他地方10，11。10,其中，两种HF表型遇到心肌重塑和信号转导通路激活导致氧化应激升高状态的证据。这与代谢重塑、基因表达改变和蛋白质的翻译后修饰变化有关，在重塑过程10、12,12中完全发挥作用。第一种是中度重塑和早期收缩功能障碍 （MOD） 的表型，第二种是表型收缩HF （HFrEF）。
HF的PO模型优于HF的心肌梗塞（MI）模型，因为PO诱导的环壁和经间壁应力均匀分布于心肌的所有段。然而，这两种模型在PO10、11和梗死大小1113、14,14的严重程度上都存在变异性，在梗死部位15处伴有强烈的炎症和疤痕，胸壁和周围组织也附着，这在HF的MI模型中观察到。,此外，大鼠PO诱导HF模型是具有挑战性的创造，因为它与高死亡率和失败率10相关，只有20%的手术大鼠开发MODHF表型10。
MOD是一个有吸引力的HF表型，构成传统创建的HFrEF表型的演变，因为它允许早期瞄准信号转导通路，在心肌重塑中发挥作用，特别是当它涉及到线粒体动力学和功能的扰动，心肌代谢，钙循环和细胞外基质重塑。这些病理生理学过程在MOD HF表型11中非常明显。在本手稿中，我们描述了如何创建 MOD 和 HFrEF 表型，并在执行提升主动脉带 （AAB） 过程时解决陷阱。我们还详细介绍了如何通过回声心动法来最好地描述两种高频表型，MOD和HFrEF，以及如何将它们与其他未开发严重PO或开发严重PO和同心重塑但无显著偏心重塑的表型区分开来。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Adson forceps</td>
			<td>F.S.T.</td>
			<td>11019-12</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>Alm chest retractor with blunt teeth</td>
			<td>ROBOZ</td>
			<td>RS-6510</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>Graefe forceps, curved</td>
			<td>F.S.T.</td>
			<td>11152-10</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>Halsted-Mosquito Hemostats, straight</td>
			<td>F.S.T.</td>
			<td>13010-12</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>Hardened fine iris scissors, straight</td>
			<td>Fine Science Tools F.S.T.</td>
			<td>14090-11</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>hemoclip traditional-stainless steel ligating clips</td>
			<td>Weck</td>
			<td>523435</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>Mayo-Hegar needle holder</td>
			<td>F.S.T.</td>
			<td>12004-18</td>
			<td>surgical tool</td>
		</tr>
		<tr>
			<td>mechanical ventilator</td>
			<td>CWE inc</td>
			<td>SAR-830/AP</td>
			<td>mechanical ventilator for small animals</td>
		</tr>
		<tr>
			<td>Weck stainless steel Hemoclip ligation</td>
			<td>Weck</td>
			<td>533140</td>
			<td>surgical tool</td>
		</tr>
	</tbody>
</table>

a rat model of pressure overload induced moderate remodeling and systolic dysfunction as opposed to overt systolic heart failure

为了对损伤（如心肌梗死、长期高血压或心毒性剂）的反应，心脏最初通过激活信号转导途径进行适应，在短期内抵消心脏肌细胞损失或壁应力的增加。然而，这些通路的长期激活变得有害，导致心脏重塑的开始和传播，导致左心室几何形状的变化和左心室体积的增加;在收缩性心力衰竭 （HF） 患者中看到的现象型。在这里，我们描述了一个大鼠模型的压力过载诱导适度重塑和早期收缩功能障碍（MOD），通过上升主动脉带（AAB）通过血管夹与2毫米2.手术在200克斯普拉格-道利大鼠中进行。MOD HF 表型在 AAB 后 8-12 周发展，通过回声心动图进行非侵入性特征。先前的研究表明，激活信号转导途径，改变基因表达和后转化后蛋白质在MOD HF表型模仿那些在人类收缩HF看到;因此，使MOD HF表型成为转化研究的合适模型，以识别和测试HF中潜在的治疗性抗重塑靶点。MOD HF 表型与表状收缩HF表型相比的优点是，它允许识别早期重塑过程和早期应用治疗干预的分子靶点。MOD HF 表型的局限性是，它可能无法模仿导致人类收缩HF的疾病谱。此外，这是一个具有挑战性的表型创建，因为AAB手术与高死亡率和失败率相关，只有20%的手术大鼠开发所需的HF表型。

在AAB之后8-12周内发育的HF表型的表型特征，可以很容易地通过回声心动图进行。图 1A中介绍了 Sham、AAB 后第 3 周、MOD 和 HFrEF 表型的代表性 M 模式图像。图 1B和图 1C分别显示了用于创建 MOD HF 表型和 HFrEF 表型的血管夹大小。LV 端分量 （LVEDV） 和端收缩 （LVESV） 卷可以使用区域?...

Watch this Scientific Journal Video about A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure at JoVE.com

A Rat Model of Pressure Overload Induced Moderate Remodeling and Systolic Dysfunction as Opposed to Overt Systolic Heart Failure

我们描述了压力过载诱导中度重塑和早期收缩功能障碍的大鼠模型的创建，其中在启动改造过程过程中涉及的信号转导通路被激活。这种动物模型将有助于确定分子靶点，用于应用早期治疗性抗重塑策略治疗心力衰竭。

压力过载诱导中度重塑和收缩功能障碍的大鼠模型，而不是过度收缩性心力衰竭

In response to an injury, such as myocardial infarction, prolonged hypertension or a cardiotoxic agent, the heart initially adapts through the activation ...

大鼠压力过载诱导中度改造和早期收缩功能障碍模型是以前创建的大鼠压力过载引起的收缩性心力衰竭模型的较温和版本。我喜欢的研究，研究心脏重塑的启动和传播的途径，特别是因为它涉及到代谢重塑，心肌功能障碍，和钙循环。在开始手术之前，通过预切七英寸的塑料来调整血管血夹结扎工具，根据所需的心力衰竭模型将夹子修改到适当的内部区域。接下来，确认麻醉大鼠对胎儿反射缺乏反应，并在右侧侧胸区剃光右轴下的头发。将动物的四肢用塑料解剖板固定，用16个量表的血管瘤对动物进行插管。启动机械通风，潮汐体积为每分钟 50 个周期，氧气的一小部分为 21%。每次呼吸时，应观察胸壁的对称上升。小心地将动物放在其左侧，以 U 形方式弯曲尾巴。然后轻轻地将尾巴胶带胶带固定到塑料板上，然后用碘酮对裸露的皮肤进行消毒。使用手术刀，在右轴下一厘米的右轴区进行一到两厘米的水平皮肤切口，并解剖胸肌层，直到达到胸肋骨笼。在第二根和第三根肋骨之间做一厘米的胸腔切除术，在轻轻解剖胸腺的两个叶之前，将胸部缩回器放入切口中。将叶推到一边，使用弯曲的灰色钳子小心地从优越的维纳卡瓦中解剖上升的动脉。一旦提升大动脉被分离，使用钳子小心地抬起容器，并在上升大动脉周围放置血管夹。然后使用2-0单丝缝合线关闭胸部，然后通过 A-3-0 锥形缝合缝合胸部的肌肉层，然后用尼龙3-0单丝缝合线关闭皮肤。对于超声心动图成像，在进行整形后，从大鼠的前部胸部去除头发，将动物稳定在塑料解剖板上的超活位置。获取 2D 副星长轴和 2D 副星短轴视图剪辑在子宫颈肌肉的水平。从膜肌水平的短抛星轴视图获取 M 模式图像，以测量支那罗的左心室隔膜和后壁厚度以及左心室端舒张和端收缩直径。获取 2D M 模式短副星轴视图图像在中腹肌的水平，作为参考，以获得可靠的串行和随后的左心室测量。然后在主心阀层获取长副星轴视图的M模式图像，以评估相对主双左中庭直径和端膜。心脏衰竭表型的特征，在上升大音带后发展8至12周，可以很容易地通过超声心动图进行。2D 长副星轴和 2D 短副星轴超声心动图视频剪辑可用于测量假和 MOD 心力衰竭动物的左心室长度和末心室长度和面积。在此 2D 短副星轴视图中，与假超声心动图图像中左心室的外观相比，可以观察到左心室肥大和 MOD 表型的增加。MOD 心力衰竭表型中的左心室和舒张体积通常介于 600 到 700 微升之间，很少有动物表现出大于 700 微升的末舒张体积。MOD 表型中的左心室和收缩体积范围在 120 到 160 微升之间。在这些代表性压力体积循环跟踪的耻辱周三下降后大音带，MOD 和公开收缩性心力衰竭动物，左心室最大压力在第八周显著增加在 MOD 和过度收缩性心力衰竭动物相比，第三周下降后大音带动物。由于动物和大动脉的生长不匹配，在上升大动脉的固定造成的狭窄。此外，与假动物相比，第三周后 AAB 动物在三周内得到充分补偿，左心室、舒张和收缩量减少。值得注意的是，大鼠压力过载诱发心力衰竭模型与高死亡率和失败率相关，只有约20%的大鼠经历大音带过渡，以发展MOD心力衰竭表型。要记住的最重要的事情是通过超声心动图正确描述动物的表型，以便缩小同一群体内动物之间的生物变异。在更动态的评估中，使用压力体积循环导管可用于评估松弛、收缩功能障碍和眼僵硬。

Research

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主动脉原位移植大鼠模型，研究慢性血管病变的发展

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant ...

科研

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Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

大鼠颈动脉球囊损伤模型试验抗血管重建治疗

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

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

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 ...

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

心动过速诱发的心肌病作为猪慢性心力衰竭模型的研究

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment ...

Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction

代谢综合征心力衰竭模型大鼠心房心肌细胞的分离与保留射血分数的关系

In this article, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of ...

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

压力超载诱发右室肥厚和衰竭的肺动脉扣条柱模型

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary ...

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

建立干细胞治疗心肌梗塞心力衰竭的猪模型

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

An Image Guided Transapical Mitral Valve Leaflet Puncture Model of Controlled Volume Overload from Mitral Regurgitation in the Rat

大鼠中三极重化控制体积过载的图像引导透射斜线阀传单穿刺模型

Mitral regurgitation (MR) is a widely prevalent heart valve lesion, which causes cardiac remodeling and leads to congestive heart failure. Though the ...