支持这项研究是由美国国家心脏，肺和血液研究所资助R01-HL-77921和-86400（古奇奥尼JM）。

1。 Algisyl LVR植入手术（视频） <ol><li> Algisyl LVR（LONESTAR心，加利福尼亚Laguna Hills）是一个由两部分组成的钙 - 海藻酸凝胶。的Na + -海藻酸成分是4.6％甘露糖醇的Ca 2 + -海藻酸成分包括不溶于水的颗粒悬浮在无菌的4.6％的甘露糖醇溶液（0点27）的无菌水溶液。 </li><li>种植体植入的程序，可以使用标准的胸骨切开术或小前开胸有限跳动的心脏上进行。体外循环的程序是没有必要的。 </li><li>使用前右，心肌内注射（00:33）到一个注射器通过结合这两种成分混合的Na + -海藻酸成分和钙 -海藻酸成分。 </li><li> 2分钟后，两种不同类型的藻酸盐将交叉链接和形成凝胶，准备植入物放置在心肌中的方式从一个注射挠度。 </li><li>确定中旬心室游离壁的LV中间左室心尖部和基地（00:44） </li><li>从安特罗隔槽在心室中期水平，在一个约45度角插入针头，注射0.3cc的Algisyl LVR慢慢每秒（0.1毫升），在一个不间断的运动（01:15）。 </li><li>重复注射液（步骤6）在一个单一的线（圆周）沿中旬心室水平在10至19个站点，开始从的安特罗室间隔槽和止在枕颈后的隔槽。由心室，间距相隔约1厘米的植入物的大小取决于植入物的数量。 </li></ol> 2。使用数学建模量化左室压力<ol><li>使用数学模型来量化左心室壁应力之前，必须已经获得了磁共振影像（MRI）包含LV的病人的短轴与长轴切面。阿奎sition这些图像可以使用标准MRI协议（ 如张等[20]）。 </li><li>数字化过程中从MR图像包含短轴（SA）的视图的LV的LV心内膜表面，心外膜表面。这是可以做到，使用轮廓分割对象（CSO）发现在自由软件MevisLab的库。 <ol class="lalpha"><li>在我们的实验室，我们已经创建了一个程序根据发现MevisLab CSO库模块，使一个简单的"轮廓"心内膜和心外膜的边界发现在SA鉴于MR图像包含LV。真实的三维（3D）空间中的心外膜和心内膜点，然后自动生成从这些的轮廓。 </li></ol></li><li>从第2步到一个商业软件导入的三维点，Rapidform软件（INUS科技公司，Sunnyvale，CA），创建的LV心外膜和心内膜表面初始图形交换规范（IGES）格式。 Rapidform软件创建这些IGES表面所使用的步骤是: <ol class="lalpha"><li>插入/导入。 </li><li>创建多边形网格。 </li><li>输出IGES表面。 </li></ol></li><li>导入IGES表面进入商业软件TrueGrid创建一个有限元网格的LV。 <ol class="lalpha"><li>填补空间之间的心内膜和心外膜表面的八个节点的的三线性砖元件。在一般情况下，网丝，含约3000的3个元素的元素，通过壁厚足以进行建模的LV 21。 </li><li>一旦完成后，导出网格的有限元求解器LS-DYNA（LSTC，利弗莫尔，CA）作为输入甲板。更多细节在此过程中，可以发现在古奇奥尼等 23。 </li></ol></li><li>分配肌纤维方向，使用我们的内部软件的"偷心"，修改输入甲板TrueGrid出口。作为一个向量的每个元素中更紧密分配肌纤维方向器到本地心外膜的切平面平行的。这个向量是相对于本地的圆周方向上测得的角度取向。在人类的LV，这个角度被设置为线性变化的整个壁厚从心外膜，心内膜23处的60°-60°。 </li><li>写边界条件和分配心肌材料模型中的元素从第5步输入甲板。 <ol class="lalpha"><li> LV基地使用关键字"SPC"LS-DYNA施加节点位移。的的心外膜基底环中的节点是固定的，上面的LV基地节点的其余部分被限制为仅在基底面移动。 </li><li>分配的构成的法律或描述应力应变关系（见"简介"）的所有元素，使用关键字"MAT"材料标识128 LS-DYNA。 </li><li>心内膜定义元素的表面施加压力边界条件，使用关键字"LOAD_分部"。 </li><li>定义使用关键字"DEFINE_CURVE"的压力 - 时间的负荷曲线。 <ol class="lroman"><li>为了模拟舒张结束，规定时间20mmHg以下规定的舒张末压（EDP）的压力迅速增加。的压力保持恒定在电子数据处理（EDP），并有足够的时间，然后允许为LV达到稳态。 </li><li>为了模拟收缩期结束，规定的压力迅速增加从舒张末期状态，随着时间的推移，直到规定的端部达到125mmHg的收缩压（ESP）。的压力保持恒定在ESP和足够的时间，然后允许为LV达到稳态。 </li></ol></li></ol></li><li>导入完成输入甲板进入商用有限元求解器LS-DYNA计算室壁应力和低压腔体积年底舒张和收缩结束。 </li><li>调整材料的参数反映了被动的刚度和心肌收缩性未直到计算左心室腔容积匹配的舒张和收缩结束结束时MRI测定的体积。 </li></ol>

<ol>
	<li>Yin, F. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ventricular+wall+stress.">Ventricular wall stress.</a> Circ. Res. 49 (4), 829-842 (1981).</li><li>Grossman, W. <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:+useful+adaptation+or+pathologic+process.">Cardiac hypertrophy: useful adaptation or pathologic process.</a> Am. J. Med. 69 (4), 576-584 (1980).</li><li>Swynghedauw, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+functional+adaptation+of+contractile+proteins+in+cardiac+and+skeletal+muscles.">Development and functional adaptation of contractile proteins in cardiac and skeletal muscles.</a> Physiol. Rev. 66 (3), 710-771 (1986).</li><li>Komuro, I., Kurabayashi, M., Takaku, F., Yazaki, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+ofcellular+oncogenes+in+the+myocardium+during+the+developmental+stage+and+pressure-overloaded+hypertrophy+of+the+rat+heart.">Expression ofcellular oncogenes in the myocardium during the developmental stage and pressure-overloaded hypertrophy of the rat heart.</a> Circ. Res. 62 (6), 1075-1079 (1988).</li><li>Schunkert, H., Dzau, V. J., Tang, S. S., Hirsch, A. T., Apstein, C. S., Lorell, B. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+rat+cardiac+angiotensin+converting+enzyme+activity+and+mRNA+expression+in+pressure+overload+left+ventricular+hypertrophy:+effect+on+coronary+resistance,+contractility,+and+relaxation.">Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy: effect on coronary resistance, contractility, and relaxation.</a> J. Clin. Invest. 86 (6), 913-920 (1990).</li><li>Aikawa, Y., Rohde, L., Plehn, J., Greaves, S. C., Menapace, F., Arnold, M. O., Rouleau, J. L., Pfeffer, M. A., Lee, R. T., Solomon, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+wall+stress+predicts+ventricular+remodeling+after+anteroseptal+myocardial+infarction+in+the+Healing+and+Early+Afterload+Reducing+Trial+(HEART):+an+echocardiography-based+structural+analysis.">Regional wall stress predicts ventricular remodeling after anteroseptal myocardial infarction in the Healing and Early Afterload Reducing Trial (HEART): an echocardiography-based structural analysis.</a> Am. Heart J. 141 (2), 234-242 (2001).</li><li>Hung, C. L., Verman, A., Uno, H., Shin, S. H., Bourgoun, M., Hassanein, A. H., McMurray, J. J., Velazquez, E. J., Kober, L., Pfeffer, M. A., Solomon, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=VALIANT+investigators.+Longitudinal+and+Circumferential+Strain+Rate,+Left+Ventricular+Remodeling,+and+Prognosis+After+Myocardial+Infarction.">VALIANT investigators. Longitudinal and Circumferential Strain Rate, Left Ventricular Remodeling, and Prognosis After Myocardial Infarction.</a> J. Am. Coll. Cardiol. 56 (22), 1812-1822 (2010).</li><li>Mann, D. L., Acker, M. A., Jessup, M., Sabbah, H. N., Starling, R. C., Kubo, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+evaluation+of+the+CorCap+Cardiac+support+device+in+patients+with+dilated+cardiomyopathy.">Clinical evaluation of the CorCap Cardiac support device in patients with dilated cardiomyopathy.</a> Ann. Thorac. Surg. 84 (4), 1226-1235 (2007).</li><li>Grossi, E. A., Patel, N., Woo, J. Y., Goldberg, J. D., Schwartz, C. F., Subramanian, V., Feldman, T., Bourge, R., Baumgartner, N., Genco, C., 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=for+the+RESTOR-MV+Study+Group.+Outcomes+of+the+RESTOR-MV+trial+(randomized+evaluation+of+a+surgical+treatment+for+off-pump+repair+of+the+mitral+valve).">for the RESTOR-MV Study Group. Outcomes of the RESTOR-MV trial (randomized evaluation of a surgical treatment for off-pump repair of the mitral valve).</a> J. Am. Coll. Cardiol. 56 (24), 1984-1993 (2010).</li><li>Athanasuleas, C. L., Stanley, A. W. H., Buckberg, G. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restoration+of+contractile+function+in+the+enlarged+left+ventricle+by+exclusion+of+remodeled+akinetic+anterior+segment:+surgical+strategy,+myocardial+protection+and+angiographic+results.">Restoration of contractile function in the enlarged left ventricle by exclusion of remodeled akinetic anterior segment: surgical strategy, myocardial protection and angiographic results.</a> J. Card. Surg. 13 (6), 418-428 (1998).</li><li>Jones, R. H., Velazquez, E. J., Michler, R. E., Sopko, G., Oh, J. K., O'Connor, C. M., Hill, J. A., Menicanti, L., Sadowski, Z., Desvigne-Nickens, P., Rouleau, J. L., Lee, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=STICH+Hypothesis+2+Investigators.+Coronary+bypass+surgery+with+or+without+surgical+ventricular+reconstruction.">STICH Hypothesis 2 Investigators. Coronary bypass surgery with or without surgical ventricular reconstruction.</a> N. Engl. J. Med. 360 (17), 1705-1717 (2009).</li><li>Buckberg, G. D., Athanasuleas, C. L., Wechsler, A. S., Beyersdorf, F., Conte, J. V., Strobeck, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+STICH+trial+unravelled.">The STICH trial unravelled.</a> Eur. J. Heart Fail. 12 (10), 1024-1027 (2010).</li><li>Sabbah, H. N., Wang, M., Jiang, A., Ilsar, I., Sabbah, M. S., Helgerson, S., Peterson, R., Tarazona, N., Lee, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Circumferential+mid-ventricular+intramyocardial+injections+of+alginate+hydrogel+improve+left+ventricular+function+and+prevent+progressive+remodeling+in+dogs+with+chronic+heart+failure.">Circumferential mid-ventricular intramyocardial injections of alginate hydrogel improve left ventricular function and prevent progressive remodeling in dogs with chronic heart failure.</a> Circulation. 120, S912 .</li><li>Yu, J., Christman, K. L., Chin, E., Sievers, R. E., Saeed, M., Lee, 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=Restoration+of+left+ventricular+geometry+and+improvement+of+left+ventricular+function+in+a+rodent+model+of+chronic+ischemic+cardiomyopathy.">Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy.</a> J. Thorac. Cardiovasc. Surg. 137 (1), 180-187 (2009).</li><li>Lee, R. J., Hinson, A., Helgerson, S., Bauerschmitt, R., Sabbah, H. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymer-based+restoration+of+left+ventricular+mechanics.">Polymer-based restoration of left ventricular mechanics.</a> Cell Transplant. 22 (3), 529-533 (2013).</li><li>Huisman, R. M., Elzinga, G., Westerhof, N., Sipkema, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+left+ventricular+wall+stress.">Measurement of left ventricular wall stress.</a> Cardiovasc. Res. 14 (3), 142-153 (1980).</li><li>Zhang, Z., Tendulkar, A., Sun, K., Saloner, D. A., Wallace, A. W., Ge, L., Guccione, J. M., Ratcliffe, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+the+Young-Laplace+law+and+finite+element+based+calculation+of+ventricular+wall+stress:+implications+for+post+infarct+and+surgical+ventricular+remodeling.">Comparison of the Young-Laplace law and finite element based calculation of ventricular wall stress: implications for post infarct and surgical ventricular remodeling.</a> Ann. Thorac. Surg. 91 (1), 150-156 (2011).</li><li>Guccione, J. M., McCulloch, A. D., Waldman, L. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Passive+material+properties+of+intact+ventricular+myocardium+determined+from+a+cylindrical+model.">Passive material properties of intact ventricular myocardium determined from a cylindrical model.</a> J. Biomech. Eng. 113 (1), 42-55 (1991).</li><li>Guccione, J. M., Waldman, L. K., McCulloch, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanics+of+active+contraction+in+cardiac+muscle:+Part+II--Cylindrical+models+of+the+systolic+left+ventricle.">Mechanics of active contraction in cardiac muscle: Part II--Cylindrical models of the systolic left ventricle.</a> J. Biomech. Eng. 115 (1), 82-90 (1993).</li><li>Zhang, P., Guccione, J. M., Nicholas, S. I., Walker, J. C., Crawford, P. C., Shamal, A., Acevedo-Bolton, G., Guttman, M. A., Ozturk, C., McVeigh, E. R., Saloner, D. A., Wallace, A. W., Ratcliffe, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endoventricular+patch+plasty+for+dyskinetic+anteroapical+left+ventricular+aneurysm+increases+systolic+circumferential+shortening+in+sheep.">Endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm increases systolic circumferential shortening in sheep.</a> J. Thorac. Cardiovasc. Surg. 134 (4), 1017-1024 (2007).</li><li>Wenk, J. F., Klepach, D., Lee, L. C., Zhang, Z., Ge, L., Tseng, E. E., Martin, A., Kozerke, S., Gorman, J. H. 3. r. d., Gorman, R. C., Guccione, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=First+evidence+of+depressed+contractility+in+the+border+zone+of+a+human+myocardial+infarction.">First evidence of depressed contractility in the border zone of a human myocardial infarction.</a> Ann. Thorac. Surg. 93 (4), 1188-1193 (2012).</li><li>Guccione, J. M., Kassab, G. S., Ratcliffe, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Computational cardiovascular mechanics: modeling and applications in heart failure. , (2010).</li><li>Streeter, D. D., Spotnitz, H. M., Patel, D. P., Ross, J., Sonnenblick, E. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fiber+Orientation+in+the+Canine+Left+Ventricle+during+Diastole+and+Systole.">Fiber Orientation in the Canine Left Ventricle during Diastole and Systole.</a> Circ. Res. 24 (3), 339-347 (1969).</li></ol>

周子扬先生是朗星心，公司雇员

Algisyl LVR注射疗法注射进入左室游离壁材料以降低室壁应力为扩张型心肌病患设计的一种新的治疗。这种治疗方法已在临床前和临床研究15渐露头角。自2012年2月以来一直在进行一项随机对照研究，以评估这种治疗严重的心脏衰竭患者（增加HF）LV隆胸的方法。 多个迭代的产品正在开发针对不同细分医师和临床需要。心胸外科医生在手术的产品版本，海藻酸钠交付在一个标准的注射器和自定义针系统专为外科医生进行注射，通过一个小切口在胸部手术（最小开胸）。一颗跳动的心脏上进行植入手术。藻酸盐的物理性能，液压后，注射到心肌肥犊类似心肌舒张，并成为一个永久的植入物。预期总手术过程的持续时间不超过60分钟，在大多数情况下，病人的曝光限制在最小的麻醉时间。第二个产品版本，可提供的程序，可以进行介入心脏病学专家和其他专家，在一些孤立的情况下，在一种非侵入性或混合性心脏病学实验室与心脏衰竭的病人。它也将允许研究急性效果。 使用数学建模量化左心室压力用数学建模的方法，用有限元方法是目前唯一的方式来精确量化体内局部室壁应力心室。结合数学建模，医疗成像如MRI，使人们能够在特定病人的VEN计算体内局部室壁应力tricles，以帮助了解这些心室的功能状态和量化注射治疗的患者的机械效应。 尽管我们已经处理的LV，在这里作为一种均匀的材料，这种方法可以是（已）的适用范围，在非均质心室，特别是量化的被检体内的室壁应力时，心肌梗死是本。在这种情况下，边界梗死和及其相邻borderzone有从MRI使用钆作为对比剂的被识别。 TrueGrid导入这些边界创建纯粹居住的元素，每个不同的区域内，即，梗死，的borderzone和偏远地区。材料参数反映病理变化在每个区域可以被分配通过LS-DYNA中各个元素。心肌梗死的病人，使用体内心肌劳损从标签MRI测量这些参数已被发现21。谁需要手术血运重建的患者往往会出现房颤，在手术后的时期，这是与质量很差标签MRI数据。这类患者也需要从手术休养几天。因此，三维超声心动图和斑点追踪可能会是一个更合适的成像方式和心肌应变测量技术比标签磁共振成像研究外科手术的急性效应。 最后，我们使用的商业软件Rapidform软件，Truegrid和LS-DYNA在这个过程中产生心室患者特定的数学模型，因为我们发现他们是在完成各自的任务效率一般。然而，其他的软件是可用的，如腕尺（用于生成有限元网格）和Abaqus（有限元求解器），也可能是适合建立数学模型的心室。

室壁应力减少被认为是在治疗心脏衰竭1的基石。在其最简单的形式给出的拉普拉斯定律，室壁应力心室和左心室压力的直径成正比，心室的壁厚是成反比的。人们普遍认为，室壁应力增加负责的不良重塑的过程中，逐步成为心室扩张，最终导致心脏衰竭2。临床和动物研究表明，增加的壁应力诱导的蛋白质，收缩元件的合成和基因表达，支持重塑过程3,4,5。壁压力增加也被证明是一个独立的预测后续左室重构6,7。 交流，已经制定了许多新的手术治疗方法和设备entral目的是降低室壁应力力图防止和扭转8,9,10患者心脏衰竭的进展。虽然这些治疗方法共享相同的目标，他们不同的方式实现它。例如，手术减少心室程序10旨在通过手术降低左心室扩张的大小，以减少室壁应力，但其结果是一个争论的主题11,12。 近日，注射液的生物相容性材料，Algisyl LVR，进入左心室扩张型心肌病的治疗在医学界已经获得了相当的关注。这种治疗方法已被证明是有效的预防或即使扭转心脏衰竭的进展在动物研究中13,14和，最近一段时间，在人类临床试验15。相反到其他设备，治疗目的是为了减少室壁应力注入材料到左心室壁加厚。 详细了解室壁应力，特别是在人类，但是，仍然是难以捉摸的。这种缺乏了解主要是因为力或应力不能直接测量，在完整的心室16。虽然封闭形式的解析，如拉普拉斯定律方程可以估算左心室壁的压力，他们开发基于严格的假设，其中包括轴对称的LV，材料的各向同性和同质内的LV。由于这些因素，室壁应力预测在实际LV，使用拉普拉斯的法律是不准确的17。要消除这些限制，以获得更准确的预测数学建模室壁应力，采用有限元（FE）方法与特定病人的心室几何应使用简化拉普拉斯的第17条代替。 有限元法是一种NUmerical技术，经常被用来解决一系列偏微分方程（PDE）描述的边界值问题。这种方法是特别有用的，当一个封闭的形式的解决方案是难以或不能获得解析。在LV的数学模型用于量化室壁应力的背景下，偏微分方程组力学平衡方程（线性动量平衡）描述的LV LV的内膜表面运动时，施加压力或负荷。当FE方法被使用时，左心室壁被分成相互连接的子域或元素（通常有8个角节点六面体），根据一个规定的应力 - 应变关系的心肌变形。 在被动充盈舒张和收缩的主动收缩期间的LV描述大变形的应力 - 应变关系，此前已在大型动物研究验证。 LV是仿照约3倍，更严厉的肌纤维方向上比在方向垂直于肌纤维方向在舒张期18。在收缩期的主动收缩是仿照通过增加沿肌纤维方向上的刚度的LV。这种刚度增加是时间的函数，并依赖于实验确定的变量，如细 ​​胞内钙浓度和肌节长度19。 使用此规定的应力 - 应变关系的心肌，有限元方法计算负载（s）适用于LV的新的基于节点的位置。一旦新的节点位置的计算，所得到的应变和应力（变形的量度）可确定在每个元素中产生的应变和应力分布的LV内。 在这里，我们勾勒出所需的步骤，植入患者的Algisyl LVR，并创建相应的特定病人的LV治疗前后的数学模型来量化的左心室壁应力。

<table><tbody><tr><td colspan="4">&lt;strong&gt;REGENTS&lt;/strong&gt;</td></tr><tr><td>Na&lt;sup&gt;+&lt;/sup&gt;-Alginate </td><td>LoneStar Heart, Inc</td><td></td><td></td></tr><tr><td>Ca&lt;sup&gt;2+&lt;/sup&gt;-Alginate </td><td>LoneStar Heart, Inc</td><td></td><td></td></tr><tr><td colspan="4">&lt;strong&gt;EQUIPMENT&lt;/strong&gt;</td></tr><tr><td>MevisLab</td><td>Mevis Medical Solution</td><td></td><td></td></tr><tr><td>TrueGrid</td><td>XYZ Scientific Application, Inc</td><td></td><td></td></tr><tr><td>Rapidform</td><td>Inus Technology, Inc</td><td></td><td></td></tr><tr><td>LS-Dyna</td><td>Livermore Software Technology Corporation</td><td></td><td></td></tr></tbody></table>

reduction in left ventricular wall stress and improvement in function in failing hearts using algisyl-lvr

注射，治疗根据临床开发，Algisyl LVR用于治疗扩张型心肌病。这种治疗方法最近被用于第一次在有症状的心脏衰竭的病人。所有患者的左心室（LV），心功能明显改善，表现为持续减少的LV体积和墙体应力。在这里，我们描述了这种新的治疗方法和所采用的方法来量化其对左心室壁应力和功能。 algisyl-LVR的Na + -海藻酸和Ca 2 + -海藻酸的生物聚合物凝胶组成。的处理流程进行了由这两种成分混合，然后把它们合并成一个注射器用于心肌内注射。此混合物注入在10至19之间的中间位置的患者的左心室游离壁的基部和先端。 磁共振成像（MRI），连同数学建模，用来量化这种治疗的效果，患者治疗前，并在不同时间点的恢复过程中。心外膜和心内膜表面首先从MR图像进行数字化重建LV几何收缩末期和舒张末期。然后从这些重建表面测量左室腔体积。 建立数学模型的LV从这些MRI重建表面区域肌纤维应力的计算。被构造成使得每个LV模式1）根据先前验证的应力 - 应变关系的心肌变形，以及2）的低压腔的容积从这些模型预测在舒张末期和收缩末期相匹配的相应的MRI测定的体积。充盈规定的舒张末压加载LV内膜的表面模拟。收缩期收缩同时加载结束模拟表面ocardial一个规定最终收缩压和加入活跃收缩肌纤维方向。区域肌纤维舒张末期和收缩末期压力计算的应力 - 应变关系的基础上，从变形的LV。

到LV游离壁变厚，并且连续注射的Algisyl-LVR的LV的大小随着时间的推移降低。在MRI的LV在患者体内的收缩期结束时，接收Algisyl-LVR（ 图1）的前个月和6个月后，左心室壁的增厚和减少的LV的大小是显而易见的。 图2示出左心室壁应力的量化中所涉及的每个步骤的结果。在图2a中，心外膜和心内膜的边缘确定的LV从短轴观中的MRI和轮廓的使用MevisLab的。将得到的IGES心内膜表面（蓝色）和心外膜表面（红色）从Rapidform软件创建使用图2b中所示的轮廓点。在此之后，心内膜和心外膜表面之间的空间填充有8节点的三线性砖元件使用TrueGrid（ 图2c的 </strONG&gt;）。每个元素中定义的肌纤维方向的载体，然后计算更紧密。这些向量显示为黑色箭头在图2d和左心室壁的切片（蓝色）显示左心室壁之间的肌纤维方向的变化如前面所述。在图2e中，在LV上示出所施加的边界条件，即，压力和位移。所施加的压力所示，箭头指向心内膜壁。在所有方向上移动，而基节点的其余部分（显示为多维数据集）中的基底面（ 图2e）被限制为仅移动限制上面的的心外膜基底环（显示为球形）的节点。最后， 图2f显示从病人治疗前的舒张末计算室壁肌纤维方向的压力。从图中很明显的应力升高，发现上面的心内膜和区域左心室壁薄。 <img src="/files/ftp_upload/50096/50096fig1.jpg" alt="图1" fo:content-width="4.5in" fo:src="/files/ftp_upload/50096/50096fig1highres.jpg"/> 图1。影响Algisyl对病人的LV（箭头）6个月后，如磁共振图像上看到的图像显示，LV已经今非昔比，壁厚增加了6个月后。 <img src="/files/ftp_upload/50096/50096fig2.jpg" alt="图2" fo:content-width="4.71in" fo:src="/files/ftp_upload/50096/50096fig2highres.jpg" /> 图2。在量化左室壁应力。涉及的步骤（一）数字化的MR图像。（二）创建IGES表面。（c）建立有限元网格（四）分配肌纤维方向。（E）施加边界条件（f）计算室壁应力（舒张末）。请参阅文本解释。

Watch this Scientific Journal Video about Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR at JoVE.com

Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR

本文介绍了一种新型水凝胶植入失败的心和量化其影响左心室壁应力和功能的过程。这些程序已经成功应用在狗和人类。

左室壁应力和改进功能衰竭心脏使用Algisyl LVR减少

Injection of  Algisyl-LVR, a treatment under clinical development, is intended to treat  patients with dilated cardiomyopathy. This treatment was recently ...

reduction-left-ventricular-wall-stress-improvement-function-failing

Nanyang Technological University

Research

JoVE Journal

Medicine

24.2K 次观看.  UCSF/VA Medical Center. 本文介绍了一种新型水凝胶植入失败的心和量化其影响左心室壁应力和功能的过程。这些程序已经成功应用在狗和人类。

视频: Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR

Cell-based Therapy for Heart Failure in Rat: Double Thoracotomy for Myocardial Infarction and Epicardial Implantation of Cells and Biomatrix

Cardiac cell therapy has gained increasing interest and implantation of biomaterials associated with cells has become a major issue to optimize myocardial cell delivery. Rodent model of myocardial infarction (MI) consisting of Left Anterior Descending Artery (LAD) ligation has commonly been performed via a thoracotomy; a second open-heart surgery via a sternotomy has traditionally been performed for epicardial application of the treatment. Since the description of LAD ligation model, post-surgery mortality rate has dropped from 35-13%, however the second surgery has remained critical. In order to improve post-surgery recovery and reduce pain and infection, minimally invasive surgical procedures are presented.&#160;Two thoracotomies were performed, the initial one for LAD ligation and the second one for treatment epicardial administration. Biografts consisting of cells associated with solid or gel type matrices were applied onto the infarcted area.&#160;LAD ligation resulted in loss of heart function as confirmed by echocardiography performed after 2 and 6 weeks. Goldner trichrome staining performed on heart sections confirmed transmural scar formation. First and second surgeries resulted in less that 10%&#160;post-operative mortality.&#160;

Implantation of a biograft to treat myocardial infarction induced by LAD ligation in a rodent model has conventionally required two open-heart surgeries. In order to reduce mortality and provide optimal conditions for fixation of solid and gelatinous biomatrices associated with cells, minimally invasive procedures have been developed.

基于细胞治疗心脏衰竭大鼠:双开胸心肌梗死和细胞与生物基质植入心外膜

Cardiac cell therapy has gained increasing interest and implantation of biomaterials associated with cells has become a major issue to optimize myocardial ...

科研

生物工程

LAD-Ligation: A Murine Model of Myocardial Infarction

Research models of infarction and myocardial ischemia are essential to investigate the acute and chronic pathobiological and pathophysiological processes in myocardial ischemia and to develop and optimize future treatment.
Two different methods of creating myocardial ischemia are performed in laboratory rodents. The first method is to create cryo infarction, a fast but inaccurate technique, where a cryo-pen is applied on the surface of the heart (1-3). Using this method the scientist can not guarantee that the cryo-scar leads to ischemia, also a vast myocardial injury is created that shows pathophysiological side effects that are not related to myocardial infarction. The second method is the permanent ligation of the left anterior descending artery (LAD). Here the LAD is ligated with one single stitch, forming an ischemia that can be seen almost immediately. By closing the LAD, no further blood flow is permitted in that area, while the surrounding myocardial tissue is nearly not affected. This surgical procedure imitates the pathobiological and pathophysiological aspects occurring in infarction-related myocardial ischemia.
The method introduced in this video demonstrates the surgical procedure of a mouse infarction model by ligating the LAD. This model is convenient for pathobiological and pathophysiological as well as immunobiological studies on cardiac infarction. The shown technique provides high accuracy and correlates well with histological sections.

This video demonstrates how to use a fast and reliable model to study pathobiological and pathophysiological processes of myocardial ischemia.

法援署结扎：有心肌梗死的小鼠模型

Research models of infarction and myocardial ischemia are essential to investigate the acute and chronic pathobiological and pathophysiological processes ...

生物学

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction

Scientific efforts in the field of computational modeling of cardiovascular diseases have largely focused on heart failure with reduced ejection fraction (HFrEF), broadly overlooking heart failure with preserved ejection fraction (HFpEF), which has more recently become a dominant form of heart failure worldwide. Motivated by the paucity of HFpEF in silico representations, two distinct computational models are presented in this paper to simulate the hemodynamics of HFpEF resulting from left ventricular pressure overload. First, an object-oriented lumped-parameter model was developed using a numerical solver. This model is based on a zero-dimensional (0D) Windkessel-like network, which depends on the geometrical and mechanical properties of the constitutive elements and offers the advantage of low computational costs. Second, a finite element analysis (FEA) software package was utilized for the implementation of a multidimensional simulation. The FEA model combines three-dimensional (3D) multiphysics models of the electro-mechanical cardiac response, structural deformations, and fluid cavity-based hemodynamics and utilizes a simplified lumped-parameter model to define the flow exchange profiles among different fluid cavities. Through each approach, both the acute and chronic hemodynamic changes in the left ventricle and proximal vasculature resulting from pressure overload were successfully simulated. Specifically, pressure overload was modeled by reducing the orifice area of the aortic valve, while chronic remodeling was simulated by reducing the compliance of the left ventricular wall. Consistent with the scientific and clinical literature of HFpEF, results from both models show (i) an acute elevation of transaortic pressure gradient between the left ventricle and the aorta and a reduction in the stroke volume and (ii) a chronic decrease in the end-diastolic left ventricular volume, indicative of diastolic dysfunction. Finally, the FEA model demonstrates that stress in the HFpEF myocardium is remarkably higher than in the healthy heart tissue throughout the cardiac cycle.

This work introduces two computational models of heart failure with preserved ejection fraction based on a lumped-parameter approach and finite element analysis. These models are used to evaluate the changes in the hemodynamics of the left ventricle and related vasculature induced by pressure overload and diminished ventricular compliance.

与保留的弹射分数一起进行心力衰竭的隆起参数和有限元素建模

Scientific efforts in the field of computational modeling of cardiovascular diseases have largely focused on heart failure with reduced ejection fraction ...

工程学

用于 HLHS 和心血管研究的禽胚胎左心房结扎模型

Left Atrial Ligation in the Avian Embryo as a Model for Altered Hemodynamic Loading During Early Vascular Development

Due to its four-chambered mature ventricular configuration, ease of culture, imaging access, and efficiency, the avian embryo is a preferred vertebrate animal model for studying cardiovascular development. Studies aiming to understand the normal development and congenital heart defect prognosis widely adopt this model. Microscopic surgical techniques are introduced to alter the normal mechanical loading patterns at a specific embryonic time point and track the downstream molecular and genetic cascade. The most common mechanical interventions are left vitelline vein ligation, conotruncal banding, and left atrial ligation (LAL), modulating the intramural vascular pressure and wall shear stress due to blood flow. LAL, particularly if performed in ovo, is the most challenging intervention, with very small sample yields due to the extremely fine sequential microsurgical operations. Despite its high risk, in ovo LAL is very valuable scientifically as it mimics hypoplastic left heart syndrome (HLHS) pathogenesis. HLHS is a clinically relevant, complex congenital heart disease observed in human newborns. A detailed protocol for in ovo LAL is documented in this paper. Briefly, fertilized avian embryos were incubated at 37.5 &#176;C and 60% constant humidity typically until they reached Hamburger-Hamilton (HH) stages 20 to 21. The egg shells were cracked open, and the outer and inner membranes were removed. The embryo was gently rotated to expose the left atrial bulb of the common atrium. Pre-assembled micro-knots from 10-0 nylon sutures were gently positioned and tied around the left atrial bud. Finally, the embryo was returned to its original position, and LAL was completed. Normal and LAL-instrumented ventricles demonstrated statistically significant differences in tissue compaction. An efficient LAL model generation pipeline would contribute to studies focusing on synchronized mechanical and genetic manipulation during the embryonic development of cardiovascular components. Likewise, this model will provide a perturbed cell source for tissue culture research and vascular biology.

作者聚焦:左心房结扎术对禽胚胎心脏的影响和 HLHS 的影响 

Here, we present a detailed visual protocol for executing the left atrial ligation (LAL) model in the avian embryo. The LAL model alters the intracardiac flow, which changes wall shear stress loading, mimicking hypoplastic left heart syndrome. An approach to overcome the challenges of this difficult microsurgery model is presented.

禽胚胎左心房结扎作为早期血管发育期间血流动力学负荷改变的模型

Due to its four-chambered mature ventricular configuration, ease of culture, imaging access, and efficiency, the avian embryo is a preferred vertebrate ...

发育生物学

Studying Left Ventricular Reverse Remodeling by Aortic Debanding in Rodents

To better understand the left ventricular (LV) reverse remodeling (RR), we describe a rodent model wherein, after aortic banding-induced LV remodeling, mice undergo RR upon removal of the aortic constriction. In this paper, we describe a step-by-step procedure to perform a minimally invasive surgical aortic debanding in mice. Echocardiography was subsequently used to assess the degree of cardiac hypertrophy and dysfunction during LV remodeling and RR and to determine the best timing for aortic debanding. At the end of the protocol, terminal hemodynamic evaluation of the cardiac function was conducted, and samples were collected for histological studies. We showed that debanding is associated with surgical survival rates of 70-80%. Moreover, two weeks after debanding, the significant reduction of ventricular afterload triggers the regression of ventricular hypertrophy (~20%) and fibrosis (~26%), recovery of diastolic dysfunction as assessed by the normalization of left ventricular filling and end-diastolic pressures (E/e&#39;&#160;and LVEDP). Aortic debanding is a useful experimental model to study LV RR in rodents. The extent of myocardial recovery is variable between subjects, therefore, mimicking the diversity of RR that occurs in the clinical context, such as aortic valve replacement. We conclude that the aortic banding/debanding model represents a valuable tool to unravel novel insights into the mechanisms of RR, namely the regression of cardiac hypertrophy and the recovery of diastolic dysfunction.

Here we describe a step-by-step protocol of surgical aorta debanding in the well-established mice model of aortic-constriction. This procedure not only allows studying the mechanisms underlying the left ventricular reverse remodeling and regression of hypertrophy but also to test novel therapeutic options that might accelerate myocardial recovery.

研究左心室反向改造由主动脉脱体在啮齿动物

To better understand the left ventricular (LV) reverse remodeling (RR), we describe a rodent model wherein, after aortic banding-induced LV remodeling, ...

医学

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

The left atrial to femoral artery bypass (LAFAB) system is a mechanical circulatory support (MCS) device used in cardiogenic shock (CS) that bypasses the left ventricle by draining blood from the left atrium (LA) and returning it to the systemic arterial circulation via the femoral artery. It can provide flows ranging from 2.5-5 L/min depending on the size of the cannula. Here, we discuss the mechanism of action of LAFAB, available clinical data, indications for its use in cardiogenic shock, steps of implantation, post-procedural care, and complications associated with the use of this device and their management.
We also provide a brief video of the procedural component of device therapy, including the pre-placement preparation, percutaneous placement of the device via transseptal puncture under echocardiographic guidance and the post-operative management of device parameters.

The following article describes the stepwise procedure for placement of a device (e.g., Tandemheart) in cardiogenic shock (CS) that is a percutaneous left ventricular assist device (pLVAD) and a left atrial to femoral artery bypass (LAFAB) system that bypasses and supports the left ventricle (LV) in CS.

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 ...

Left Coronary Artery Ligation: A Surgical Murine Model of Myocardial Infarction

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In order to explore the pathophysiological changes after myocardial infarction and design future treatments, research models of MI are required. Permanent ligation of the left coronary artery (LCA) in mice is a popular model to investigate cardiac function and ventricular remodeling post MI. Here we describe a less invasive, reliable, and reproducible surgical murine MI model by permanent ligation of the LCA. Our surgical model comprises of an easily reversible general anesthesia, endotracheal intubation that does not require a tracheotomy, and a thoracotomy. Electrocardiography and troponin measurement should be performed to ensure MI. Echocardiography at day 28 after MI will discern heart function and heart failure parameters. The degree of cardiac fibrosis can be evaluated by Masson's trichrome staining and cardiac MRI. This MI model is useful for studying the pathophysiological and immunological alterations after MI.

Presented here is a surgical procedure for permanent ligation of the left coronary artery in mice. This model can be used to investigate the pathophysiology and associated inflammatory response after myocardial infarction.

左冠状动脉结扎术:心肌梗死的外科小鼠模型

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In ...

Left Anterior Descending Coronary Artery Ligation for Ischemia-Reperfusion Research: Model Improvement via Technical Modifications and Quality Control

Coronary heart disease is the leading cause of death globally. Complete cessation of blood flow in coronary arteries causes ST-segment elevation myocardial infarction (STEMI), resulting in cardiogenic shock and fatal arrhythmia, which are associated with high mortality. Primary coronary intervention (PCI) for recanalizing the coronary artery significantly improves the outcomes of STEMI, but advancements made in shortening the door-to-balloon time have failed to reduce in-hospital mortality, suggesting that additional therapeutic strategies are required. Left anterior descending coronary artery (LAD) ligation in rats is an animal model for acute myocardial IR research that is comparable to the clinical scenario in which rapid coronary recanalization through PCI is used for STEMI; however, PCI-induced STEMI is a technically challenging and complicated operation associated with high mortality and great variation in infarction size. We identified the ideal position for LAD ligation, created a gadget to control a snare loop, and supported a modified surgical maneuver, thereby reducing tissue damage, to establish a reliable and reproducible acute myocardial ischemia-reperfusion (IR) research protocol for rats. This is a non-survival surgery. We also propose a method for validating the quality of study results, which is a critical step for determining the accuracy of subsequent biochemical analyses.

Herein, we present a protocol focusing on the quality control of the left anterior descending coronary artery ligation by technically modifying the traditional procedure in rats for acute myocardial ischemia-reperfusion research.

左室壁应力和改进功能衰竭心脏使用Algisyl LVR减少

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基于细胞治疗心脏衰竭大鼠:双开胸心肌梗死和细胞与生物基质植入心外膜

法援署结扎：有心肌梗死的小鼠模型

与保留的弹射分数一起进行心力衰竭的隆起参数和有限元素建模

禽胚胎左心房结扎作为早期血管发育期间血流动力学负荷改变的模型

禽胚胎左心房结扎作为早期血管发育期间血流动力学负荷改变的模型

禽胚胎左心房结扎作为早期血管发育期间血流动力学负荷改变的模型

研究左心室反向改造由主动脉脱体在啮齿动物

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

左冠状动脉结扎术:心肌梗死的外科小鼠模型

用于缺血再灌注研究的左前降冠状动脉结扎术:通过技术修改和质量控制改进模型