Name: novel percutaneous approach for deployment of 3d printed coronary stenosis implants in swine models of ischemic heart disease
Uploaded: 2020-02-18T16:00:00
Description: Watch this Scientific Journal Video about Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease at JoVE.com

我们感谢加州大学洛杉矶分校转化研究成像中心和美国加州加州大学洛杉矶分校实验室动物医学系的工作人员给予的帮助。这项工作部分得到了加州大学洛杉矶分校大卫·格芬医学院放射和医学系、美国心脏协会（18TPA34170049）和退伍军人健康管理局发展委员会临床科学研究（）VA-MERIT I01CX001901）。

我们根据《动物福利法》、《国家卫生研究院》和美国心脏研究动物使用协会的指导方针进行了实验。我们的机构动物护理和使用委员会批准了动物研究协议。
1. 3D打印冠状狭窄植入物的手术前准备
<ol><li>使用钳子，在25%的肝素溶液中浸渍印刷植入物，以防止血栓形成，并允许空气干燥24小时。</li>
</ol>2. 动物主体的程序前准备
<ol><li>有雄性约克郡猪（SNS?...

<ol>
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E., Verow, A. F., Sinusas, A. J., Whayne, J. G., DiMarco, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracoronary+ethanol+ablation+in+swine:+characterization+of+myocardial+injury+in+target+and+remote+vascular+beds.">Intracoronary ethanol ablation in swine: characterization of myocardial injury in target and remote vascular beds.</a> Journal of Cardiovascular Electrophysiology. 5, 422-431 (1994).</li><li>Kraitchman, D., Bluemke, D., Chin, B., Heldman, A. W., Heldman, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+minimally+invasive+method+for+creating+coronary+stenosis+in+a+swine+model+for+MRI+and+SPECT+imaging.">A minimally invasive method for creating coronary stenosis in a swine model for MRI and SPECT imaging.</a> Investigative Radiology. 35 (7), 445-451 (2000).</li></ol>

在这项工作中，我们重点研究了冠状动脉狭窄诱导植入物的新型皮下部署策略，并表明可以重新利用母子导管，以便有效实现3D打印冠状植入物的皮下传递。在具有高成功率的猪模型中，可快速创建具有可变严重性的离散人工冠状动脉，并使用标准的人类皮下冠状动脉介入技术和设备，以微创方式创建。这些植入物在急性环境中是安全的，并且还能有效制造严重的血管造影石塞，这与血管扩张器?...

缺血性心脏病仍然是美国的头号死因。大型动物模型已用于实验，以理解和描述导致冠状动脉疾病 （CAD） 和相关并发症（包括心肌梗死、心律失常和心力衰竭）的机制，以及测试新的治疗或诊断方式。这些研究的结果有助于扩大对缺血性心脏病的理解、诊断和监测，并推进临床实践2。已经使用了一些动物模型，包括兔子、狗和猪。然而，冠状动脉瘤，特别是离散病变，很少发生在这些动物，并难以诱导可重复3。先前的工作描述了使用结扎、遮挡器或外部钳子创建人工冠状动脉。最近，我们描述了如何使用3D打印技术来制造冠状植入物，可用于皮上形成离散人工冠状体缩小4。我们使用计算机辅助设计软件，将冠状动脉植入物设计为内径和外径不同以及植入物长度不同的空心管，然后使用市售的增材进行制造。植入物是光滑，空心，3D打印管与圆边。我们设计了一个内径、外径和长度的植入物尺寸库。植入物的外径基于冠状导管的大小。内径基于气放冠状血管成形气球的大小。我们改变植入物的长度，以定制所需的灌注严重度。然而，由于缺乏专为大型动物使用而制造的电线和导管，此类设备的安全皮下交付可能具有挑战性。相反，广泛的导管、电线和支持设备可供临床用于人类冠状动脉。在这项工作中，我们将演示如何将临床级母婴冠状动脉重新用于 3D 打印冠状植入物的交付。
GuideLineer 导管 （图 1A） 是为皮下冠状动脉介入 （PCI） 开发的，用于深导管座，并增加对复杂病例5的支持。在我们的调查中，选择 GuideLineline 导管是由于对使用和可用性的熟悉，但类似的导管（如有）也可以考虑。被认为是"母子"导管（图1B），该设备适合在典型的冠状导管（"母亲"）内，是同轴柔性管（"儿童"）。该导管可以插入导丝，通过超出冠状导管末端，有效延长典型冠状导管的伸出。GuideLineer 或类似的母子导管可用作部署 3D 打印冠状植入物的附加支持。由于植入物安装在血管成形气球上，通过冠状动脉作为单元插入血管（图1B，1C），导管提供额外的支持，将植入物输送到所需的部位。通过将母子导管定位在气球近端，植入物在气球通缩和回缩期间仍保持在所需位置。尽管其结构有些牢固，但母子导管的独特能力通过导线深入冠状动脉，导管尖端处的放射性标记是植入的基本特征。
我们组装的传送装置包括典型的冠状导管、母子导管和固定在气放冠状血管成形气球上的3D打印植入物（图1B）。作为功能性输送装置，母子导管不仅为设备的交付提供了稳定的额外支持，而且作为剪切装置也得到独特的应用，在通缩和球囊去除过程中保持植入物的到位。导管尖端处的放射性标记用作组装设备的定位指南，并位于血管成形气球的近端位置。这些特性允许精确部署流量限制植入物。这个过程被设计成对动物主体的可重复、高效和人道。
在我们的应用中，母子皮下分娩技术用于创建具有焦点冠状狭窄功能的猪模型，用于评估对比度增强应力心脏灌注磁共振成像 （MRI）。然而，该技术可用于其他研究，包括冠状血管外的血管系统。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3D-Printed coronary implants</td>
			<td>Study Site Manufactured</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Amiodarone IV solution</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Amplatz Left-2 (AL-2) guide catheter (8F)</td>
			<td>Boston Scientific, Marlborough, Massachusetts, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Balance Middleweight coronary wire (0.014&#34; 300cm)</td>
			<td>Abbott Laboratories, Abbott Park, Illinois, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>COPILOT Bleedback Control valve</td>
			<td>Abbott Laboratories, Abbott Park, Illinois, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Esmolol IV solution (1 mg/kg)</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Formlabs Form 2 3D-printer with a minimum XY feature size of 150 &#181;m</td>
			<td>Formlabs Inc., Somerville, Massachusetts, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Formlabs Grey Resin (implant material)</td>
			<td>Formlabs Inc., Somerville, Massachusetts, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Gadobutrol 0.1 mmol/kg</td>
			<td>Gadvist, Bayer Pharmaceuticals, Wayne, NJ</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>GuideLiner catheter (6F)</td>
			<td>Vascular Solutions Inc., Minneapolis, Minnesota, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Heparin IV solution</td>
			<td>Surface Solutions Laboratories Inc., Carlisle, Massachusetts, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ketamine IM solution (10 mg/kg)</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Lidocaine IV solution</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Male Yorkshire swine (30-45 kg)</td>
			<td>SNS Farms</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Midazolam IV solution</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>NC Trek over-the-wire coronary balloon</td>
			<td>Abbott Laboratories, Abbott Park, Illinois, USA</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Oxygen-isoflurane 1-2% inhaled mixture</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Rocuronium IV solution</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium Pentobarbital IV solution (100mg/kg)</td>
			<td>Study Site Pharmacy</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Triphenyltetrazolium chloride stain</td>
			<td>Institution Pathology Lab</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

novel percutaneous approach for deployment of 3d printed coronary stenosis implants in swine models of ischemic heart disease

在大型动物中创建焦点冠状缩小模型的微创方法具有挑战性。使用三维（3D）打印冠状植入物进行快速原型设计，可采用皮上形成焦点冠状动脉狭窄。但是，如果不使用辅助设备，植入物的可靠交付可能很困难。我们描述了使用母子冠状动脉稳定植入物，以及将3D打印植入物有效运送到冠状动脉长度的任何所需位置。在冠状动脉镜检查下，确定了焦点冠状动脉缩小，并使用高岭土增强型第一通心脏灌注MRI评估冠状动脉狭窄功能显著性。研究表明，通过重新利用母婴冠状动脉，可以可靠地在缺血性心脏病的猪型（n = 11）中植入3D打印冠状植入物。我们的技术简化了冠状植入物的皮皮传递，以创建焦点冠状动脉狭窄闭胸猪模型，并且可以快速执行，程序故障率低。

在程序初步优化后，干预组件在30分钟内完成。所有11个受试者（100%）成功植入了植入物。在验尸时，所有11名受试者（100%）都取回了植入物。使用对角分支（沿LAD）或钝化边缘分支（沿LCX）作为位置标记，我们发现植入物在荧光导路部署和尸体解剖时的位置在11个（91%）中的10个一致植入物可检索的受试者。在一个受试者中，植入物有轻微的远端迁移，这可能与冠状硝化甘油注射为冠状痉挛引起?...

Watch this Scientific Journal Video about Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease at JoVE.com

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease

我们描述了一种新颖、经济、高效的三维印刷冠状动脉植入物的皮下递送技术，以创建缺血性心脏病的闭胸猪模型。植入物使用母子延长导管固定到位，成功率高。

在缺血性心脏病的猪模型中部署3D打印冠状动脉狭窄植入物的新颖的皮下方法

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally ...

我们的MRI兼容微创闭胸猪模型。它有助于对缺血性心脏病进行更快速的转化研究。我们已经表明，母子导管可以用来以安全快速的方式精确部署冠状动脉植入物，从而限制对动物受试者的不利影响。我们的方法可用于开发新的缺血性心脏病诊断成像技术。与一些轻微的修改，它也可以应用于其他血管疾病状态。虽然很难选择性地在小猪中对左主冠状动脉进行导管，但使用母子导管可以获得高质量的血管造影。我们的方法使我们能够诱导我们选择的血管中的焦点冠状动脉病变，并在同一天进行MRI研究。该技术的可视化演示有助于减少未来调查中的试验和错误，从而产生更可重复的结果。手术前一天，用钳子将涂层打印的植入物浸入25%的肝素溶液中。让植入物干燥24小时。在手术当天确认在30至45公斤的约克郡猪中适当水平的丁热，并使用塞尔丁格技术将动脉和静脉护套插入动物的双边股动脉和静脉。然后用肝素化普通盐水连续冲洗所有导管端口。获得血管通路后，管理5000至10000单位的肝素，以保持超过300百秒的活性凝血时间。对于血流动力学监测，使用心电图胸腔记录整个实验期间ST段、T波和心率的变化。使用压力传感器记录整个手术的连续股动脉压力。将脉搏血氧计连接到动物的耳朵，进行连续的脉搏血氧测定记录。通过所需大小的母子导管在电线冠状气球上插入放气的 NC TREK，使气球尖端延伸到导管尖端之外。将 3D 打印植入物安装到放气的血管成形气球上，使植入物位于气球的标记之间，靠近近位标记。然后使用 Instaflator 将气球充气到两到三个大气，将植入物固定到气球上，并验证植入物的位置是否更接近气球的近近半部分，以便当准备拆卸时，植入物最接近母子导管。要诱导冠状动脉造影术，在后排投影中用荧光镜C臂进行，请将控制阀连接到左或右冠状动脉导管上。通过右股动脉护套，通过 J 倾斜的导线介绍导管。在荧光镜引导下，导管推进到大音根。有选择地将导管插入左侧主冠状动脉，并在荧光镜下注射五毫升的碘化对比，以可视化左冠状动脉系统。将导管朝向左主冠状动脉进行第二次血管造影。一旦在左主冠状动脉附近或靠近位置，将一根0.014英寸300厘米的冠状动脉推进到左主冠状动脉，并进一步将导线推进到远端左前下动脉。将先前组装的母子导管与膨胀的冠状血管成形气球一起插入，并植入冠状动脉，然后沿着冠状动脉血管将组装推进到所需位置。注射五毫升的碘化对比度，以可视化在应部署冠状动脉植入物的所需位置的隐蔽缩小。一旦植入物就位，将母子导管推进到充气气球的近位标记。输送系统的几何约束允许将狭窄定位在猪冠状动脉的近端到中间部分。将气球放气，并通过母子导管将其缩回，在气球缩回时将植入物从气球上剪下来，将植入物的位置固定在容器的指定部分内。然后进行最终血管造影，记录血管内新人工狭窄的位置，并尽可能进行两次正交视图，以获得对狭窄严重程度的视觉估计。收获后，解剖前活体心脏，以暴露冠状动脉血管。请注意植入物相对于其位于其旁边的分支的位置，以检索植入物并检查容器是否严重受伤。然后用TTC拍摄心脏组织毛病理学和污渍，排除心肌梗塞。在这些应力心脏丰富的磁共振图像的冠状动脉植入物部署在近端左前下体下体动脉，植入的容器可以在休息和高峰腺苷血管扩张器应力时观察到。请注意左前下降动脉所引致灌注的段状缺陷。请记住，在冠状气球通缩之前，母子导管在稳定位置对植入物进行冲洗，以便在提取时剪切气球。现在，我们可以部署植入物，并在一天后完成整个 MR 成像研究，从而大幅减少这些实验的时机和后勤挑战。

Research

JoVE Journal

Medicine

Gene Transfer for Ischemic Heart Failure in a Preclinical Model

缺血性心力衰竭在临床前模型的转基因

Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine ...

科研

医学

Implantation of Total Artificial Heart in Congenital Heart Disease

的全人工心脏的先天性心脏病植入

In patients with end-stage heart failure (HF), a total artificial heart (TAH) may be implanted as a bridge to cardiac transplant. However, in congenital ...

Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

定量3D<em&gt;在硅片</em&gt;建模阿尔茨海默病的啮齿动物模型脑淀粉样蛋白-β吞噬（q3DISM）

Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible ...

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 ...

3D Planning and Printing of Patient Specific Implants for Reconstruction of Bony Defects

患者特异性植入物重建的三维规划与打印

We are in the midst of the 3D era in most aspects of life, and especially in medicine. The surgical discipline is one of the major players in the medical ...

Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes

使用hiPSC衍生心肌细胞的缺血性心脏病模型和基于视频的心肌细胞收缩比较

Ischemic heart disease is a significant cause of death worldwide. It has therefore been the subject of a tremendous amount of research, often with ...

Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training

干预规划和培训的3D打印心血管幻影的开发与评估

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training ...

Use of a Percutaneous Ventricular Assist Device/Left Atrium to Femoral Artery Bypass System for Cardiogenic Shock

使用经皮心室辅助装置/左心房至股动脉旁路系统治疗心源性休克

The left atrial to femoral artery bypass (LAFAB) system is a mechanical circulatory support (MCS) device used in cardiogenic shock (CS) that bypasses the ...

Large Animal Model for Evaluating the Efficacy of the Gene Therapy in Ischemic Heart

用于评估基因治疗缺血性心脏疗效的大型动物模型

Coronary artery disease is one of the significant causes of mortality and morbidity worldwide. Despite the progression of current therapeutics, a ...

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

猪模型中经皮栓塞线圈部署的心肌梗死

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization ...