Name: Advancing Cardiac Procedure Testing Prior to Embarking on Large Animal Studies (Video) | JoVE
Uploaded: 2023-08-25T15:00:00
Description: Watch this Scientific Journal Video about Advancing Cardiac Procedure Testing Prior to Embarking on Large Animal Studies at JoVE.com

我们要感谢 Gordana Vunjak-Novakovic 博士的实验室，包括 Julie Van Hassel、Mohamed Diane 和 Panpan Chen，他们允许我们使用他们实验中的心脏废物组织。这项工作得到了新泽西州巴特勒的先天性心脏缺陷联盟和马里兰州贝塞斯达的美国国立卫生研究院（5T32HL007854-27）的支持。

所有研究均按照动物护理的机构指南进行。
一、实验的注意事项和准备工作
<ol><li>使用合适的脉冲复制器 （PD） 通过 AV 模拟心输出量。PD需要能够容纳生物材料并能够进行清洁。<ol><li>利用适合测试 AV 的 PD 设置：70 mL 位移容积和 70 次/分钟心跳（5 L/min 心输出量）、收缩期心动周期的 35%、100 mmHg 平均经瓣压梯度、120 个最大压力梯度和 80 个最小压力梯度。</li>
	...

Evaluation of Hydrodynamic Properties in Mounted Porcine Aortic Valves

<ol>
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M. O., 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=Comparative+angiotomographic+study+of+swine+vascular+anatomy:+contributions+to+research+and+training+models+in+vascular+and+endovascular+surgery.">Comparative angiotomographic study of swine vascular anatomy: contributions to research and training models in vascular and endovascular surgery.</a> Journal Vascular Brasilerio. 20, 20200086 (2021).</li><li>Ho&#322;da, M. K., Klimek-Piotrowska, W., Koziej, M., Pi&#261;tek, K., Ho&#322;da, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+different+fixation+protocols+on+the+preservation+and+dimensions+of+cardiac+tissue.">Influence of different fixation protocols on the preservation and dimensions of cardiac tissue.</a> Journal of Anatomy. 229 (2), 334-340 (2016).</li><li>Ho&#322;da, M. K., Klimek-Piotrowska, W., Koziej, M., Tyrak, K., Ho&#322;da, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Penetration+of+formaldehyde+based+fixatives+into+heart.">Penetration of formaldehyde based fixatives into heart.</a> Folia Medica Cracoviensia. 57 (4), 63-70 (2017).</li><li>Spampinato, R. 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=Grading+of+aortic+regurgitation+by+cardiovascular+magnetic+resonance+and+pulsed+Doppler+of+the+left+subclavian+artery:+harmonizing+grading+scales+between+imaging+modalities.">Grading of aortic regurgitation by cardiovascular magnetic resonance and pulsed Doppler of the left subclavian artery: harmonizing grading scales between imaging modalities.</a> International Journal of Cardiovascular Imaging. 36 (8), 1517-1526 (2020).</li><li>Capps, S. B., Elkins, R. C., Fronk, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Body+surface+area+as+a+predictor+of+aortic+and+pulmonary+valve+diameter.">Body surface area as a predictor of aortic and pulmonary valve diameter.</a> The Journal of Thoracic and Cardiovascular Surgery. 119 (5), 975-982 (2000).</li><li>Baumgartner, 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=Recommendations+on+the+echocardiographic+assessment+of+aortic+valve+stenosis:+a+focused+update+from+the+European+Association+of+Cardiovascular+Imaging+and+the+American+Society+of+Echocardiography.">Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography.</a> European Heart Journal - Cardiovascular Imaging. 18 (3), 254-275 (2017).</li><li>Saisho, 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=An+ex+vivo+evaluation+of+two+different+suture+techniques+for+the+Ozaki+aortic+neocuspidization+procedure.">An ex vivo evaluation of two different suture techniques for the Ozaki aortic neocuspidization procedure.</a> Interactive Cardiovascular and Thoracic Surgery. 33 (4), 518-524 (2021).</li><li>Saisho, 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=Ex+vivo+evaluation+of+the+Ozaki+procedure+in+comparison+with+the+native+aortic+valve+and+prosthetic+valves.">Ex vivo evaluation of the Ozaki procedure in comparison with the native aortic valve and prosthetic valves.</a> Interactive Cardiovascular and Thoracic Surgery. 35 (3), (2022).</li><li>Paulsen, M. 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=Comprehensive+ex+vivo+comparison+of+5+clinically+used+conduit+configurations+for+valve-sparing+aortic+root+replacement+using+a+3-dimensional-printed+heart+simulator.">Comprehensive ex vivo comparison of 5 clinically used conduit configurations for valve-sparing aortic root replacement using a 3-dimensional-printed heart simulator.</a> Circulation. 142 (14), 1361-1373 (2020).</li><li>Al-Atassi, T., 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=Impact+of+aortic+annular+geometry+on+aortic+valve+insufficiency:+Insights+from+a+preclinical,+ex+vivo,+porcine+model.">Impact of aortic annular geometry on aortic valve insufficiency: Insights from a preclinical, ex vivo, porcine model.</a> The Journal of Thoracic and Cardiovascular Surgery. 150 (3), 656-664 (2015).</li><li>Sun, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+biomimetic+multilayered+polymeric+material+designed+for+heart+valve+repair+and+replacement.">A biomimetic multilayered polymeric material designed for heart valve repair and replacement.</a> Biomaterials. 288, 121756 (2022).</li><li>Waller, B. 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这里介绍的方法为AV的流体动力学测试提供了一个平台，以检查实验程序或新型医疗设备的效果。通过将天然主动脉瓣安装在脉冲复制机上，我们能够确定实验程序对用于研究和批准新型瓣膜假体（ISO 5840）的所有流体动力学参数的影响。这提供了一个机会，可以在大型动物模型中使用之前对程序和假体进行微调。
由于左心室流出道中缺乏环形心肌，因此固定流入段存在一些?...

主动脉瓣疾病是一个重大的公共卫生负担，尤其是主动脉瓣狭窄，影响着全世界900万人1。目前，解决这种疾病的策略正在不断发展，包括主动脉瓣修复和主动脉瓣置换术。特别是在儿科人群中，修复而不是更换瓣膜有很大的动机，因为目前可用的假体容易发生结构性瓣膜变性 （SVD） 并且不耐生长，需要随着患者的成长再次手术以重新更换。即使是用自体肺动脉瓣 （PV） 替换患病主动脉瓣 （AV） 的 Ross 手术，也需要在肺位置安装假体或移植物，该位置也受到 SVD 的影响，并且通常生长耐受性有限2。正在开发治疗主动脉瓣疾病的新方法，在应用于大型动物模型之前，需要在生物学相关背景下进行测试。
我们开发了一种用于测试猪 AV 的方法，该方法可以深入了解新型医疗设备的研究程序或应用之前和之后的瓣膜功能。通过将猪 AV 安装在市售的脉冲复制机上，我们能够比较用于研究并最终批准瓣膜假体的流体动力学特性，包括反流分数 （RF）、有效孔口面积 （EOA） 和平均正压差 （PPD）3,4.然后，在大型动物模型中使用之前，可以在生物学相关的背景下对干预进行微调，从而限制了生产可用于人类的程序或假体所需的动物数量。用于该实验的心脏可以从当地的屠宰场获得，也可以从其他实验中获得废物组织，因此没有必要仅仅为了这个实验的目的而牺牲动物。
在我们的工作中，我们使用这种方法开发了一种用于瓣膜修复和更换的新型贴片材料。我们通过对猪 AV 进行主动脉瓣新尖瓣手术（尾崎手术5、6、7）并在手术前后在脉冲复制器中对其进行测试，测试了各种贴片材料的流体动力学功能。这使我们能够根据材料的流体动力学性能对材料进行微调。因此，该方法为在大型动物模型中应用之前在AV上使用的实验程序和新型医疗设备的流体动力学测试提供了一个平台。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3D Printer</td>
			<td>Ultimaker</td>
			<td>Ultimaker S5</td>
			<td>Used for printing custom fixtures for hydrodynamic testing</td>
		</tr>
		<tr>
			<td>Crile-Wood Needle Driver</td>
			<td>Emerald Instruments</td>
			<td>2.0638.15</td>
			<td>Used for suturing ventricle</td>
		</tr>
		<tr>
			<td>Debakey Forceps</td>
			<td>Jarit</td>
			<td>320-110</td>
			<td>Used for dissection and sample preparation (can use multiple if working with an assistant)</td>
		</tr>
		<tr>
			<td>Ethanol 200 proof</td>
			<td>Decon Labs Inc.</td>
			<td>DSP-MD.43</td>
			<td>Used for fixed tissue storage</td>
		</tr>
		<tr>
			<td>Formalin 10%</td>
			<td>Epredia</td>
			<td>5701</td>
			<td>Used for tissue fixation</td>
		</tr>
		<tr>
			<td>Gerald Forceps</td>
			<td>Jarit</td>
			<td>285-126</td>
			<td>Used for dissection and sample preparation</td>
		</tr>
		<tr>
			<td>Glass jars</td>
			<td>QAPPDA</td>
			<td>B07QCP54Z3</td>
			<td>Used for tissue storage</td>
		</tr>
		<tr>
			<td>Glutaraldehyde 25%</td>
			<td>Electron Microscopy Sciences</td>
			<td>16400</td>
			<td>Used for tissue fixation</td>
		</tr>
		<tr>
			<td>HEPES 1 M buffer solution</td>
			<td>Fisher</td>
			<td>BP299-100</td>
			<td>Used to make glutaraldehyde 0.6%</td>
		</tr>
		<tr>
			<td>Mayo Scissors</td>
			<td>Jarit</td>
			<td>099-200</td>
			<td>Used for cutting suture</td>
		</tr>
		<tr>
			<td>Metzenbaum Scissors</td>
			<td>Jarit</td>
			<td>099-262</td>
			<td>Used for dissection and sample preparation</td>
		</tr>
		<tr>
			<td>O-ring</td>
			<td>Sterling Seal &#38; Supply Inc.</td>
			<td>AS568-117</td>
			<td>Used as a gasket on the end of the 3D printed fixtures</td>
		</tr>
		<tr>
			<td>Polylactic acid resin</td>
			<td>Ultimaker</td>
			<td>1609</td>
			<td>Used for 3D printing fixtures</td>
		</tr>
		<tr>
			<td>Polyproplene suture</td>
			<td>Covidien</td>
			<td>VP-762-X</td>
			<td>Used for suturing ventricle, tapered needle</td>
		</tr>
		<tr>
			<td>Pulse Duplicator</td>
			<td>BDC Laboratories</td>
			<td>HDTi-6000</td>
			<td>Used for hydrodynamic testing</td>
		</tr>
		<tr>
			<td>Silk ties</td>
			<td>Covidien</td>
			<td>S-193</td>
			<td>Used for ligating coronary arteries</td>
		</tr>
		<tr>
			<td>Tonsil Clamp</td>
			<td>Aesculap</td>
			<td>BH957R</td>
			<td>Used for coronary artery dissection</td>
		</tr>
		<tr>
			<td>Zip ties (6 inch)</td>
			<td>Advanced Cable Ties, Inc.</td>
			<td>AL-06-18-9-C</td>
			<td>Used for securing sample to fixtures, 157.14 mm long (6 inches), 2.5 mm wide</td>
		</tr>
		<tr>
			<td>Zip ties (8 inch)</td>
			<td>GTSE</td>
			<td>GTSE-20025B.1000</td>
			<td>Used for securing sample to fixtures, 203 mm long (8 inches), 2.5 mm wide</td>
		</tr>
	</tbody>
</table>

an ex vivo porcine model for hydrodynamic testing of experimental aortic valve procedures and novel medical devices

在动物模型中使用之前测试新的心脏程序和研究性医疗设备的选择是有限的。在这项研究中，我们提出了一种在脉冲复制器中安装猪主动脉瓣以评估其流体动力学特性的方法。然后，可以在执行所调查的程序和/或应用调查医疗设备之前和之后评估这些特性。由于左心室流出道中缺乏环形心肌，因此固定流入段存在一些困难。这种方法通过使用二尖瓣的前叶固定流入段，然后在流入固定装置周围缝合左心室游离壁来解决这个问题。只需将夹具插入主动脉弓上侧的切口即可固定流出段。我们发现，标本在组织固定前后具有显着不同的流体动力学特性。这一发现促使我们在测试中使用新鲜标本，在使用这种方法时应予以考虑。在我们的工作中，我们使用这种方法通过在安装的猪主动脉瓣上执行主动脉瓣新尖瓣手术（尾崎手术）来测试用于瓣膜位置的新型心内贴片材料。这些阀门在手术前后进行了测试，以评估与天然阀门相比流体动力学特性的变化。在此，我们报告了一个用于实验性主动脉瓣手术的流体动力学测试平台，该平台可以与天然瓣膜以及用于所研究手术的不同设备和技术进行比较。

An Ex Vivo Porcine Model for Hydrodynamic Testing of Experimental Aortic Valve Procedures and Novel Medical Devices

从脉冲拷贝机收集的代表性数据包括反流分数 （RF）、有效孔口面积 （EOA） 和平均正压差 （PPD）。特别是 RF 和 EOA，用于 ISO 人工瓣膜标准 （ISO 5840），如果人工瓣膜产品正在接受调查，收集这些标准非常重要。PPD 提供了有关打开瓣膜所需的压力的信息，在讨论人工瓣膜置换术时通常被引用 3,4。本实验中使用的 HDTi-6000 脉冲拷贝机（BDC Laboratories，Wheat...

Watch this Scientific Journal Video about Advancing Cardiac Procedure Testing Prior to Embarking on Large Animal Studies at JoVE.com

Advancing Cardiac Procedure Testing Prior to Embarking on Large Animal Studies (Video) | JoVE

我们提出了一种将猪主动脉瓣安装在脉冲复制器上以测试其流体动力学特性的方法。该方法可用于确定在大型动物模型中使用实验程序或新型医疗设备之前应用实验程序或新型医疗设备后流体动力学的变化。

用于实验性主动脉瓣手术和新型医疗设备流体动力学测试的 离体 猪模型

The options for testing new cardiac procedures and investigative medical devices prior to use in an animal model are limited. In this study, we present a ...

在大型动物模型中使用之前，测试新的心脏程序和研究性医疗设备的选择有限。我们的协议提供了在开始大型动物研究之前在生物学和解剖学相关背景下微调此类程序和设备的机会。在脉搏复制器上安装主动脉瓣的其他技术需要将刚性结构插入或固定在主动脉瓣环上，从而扭曲瓣膜的流体动力学特性。我们的协议提供了一种创新的方法来套管LVOT，以便所有测量的流体动力学特性都是有效的。该方法旨在评估用作瓣膜修复贴片或假体的传单替代材料的可行性。它是我们未来研究的关键工具，我们正在开发仿生聚合物材料，用作具有天然组织的耐用阀门替代品，如机械和流体动力学特性。

用于实验性主动脉瓣手术和新型医疗设备流体动力学测试的 离体 猪模型

用于实验性主动脉瓣手术和新型医疗设备流体动力学测试的离体猪模型