This work was supported by Onderzoekstoelagen grant OT/13/090 of the KU Leuven and by grant G0A3114N of the FWO-Vlaanderen.

注意：本节中描述的所有实验程序批准的机构动物护理和鲁汶大学的研究咨询委员会（项目：二千零十三分之一百五十四-B德范）。 左冠状动脉前降支1结扎<ol><li>麻醉小鼠通过的40毫克/千克腹膜内给药至70mg戊巴比妥钠的/公斤。确保鼠标达到其应有的麻醉平面，当它不再反应的公司脚趾捏。一定要确认正确麻醉之前，任何外科手术或介入这种方式。使用润滑眼药膏，以防止角膜干燥的同时，在麻醉下。步骤（丁丙诺啡0.05毫克/公斤SQ）的开始之前提供的术前麻醉2-4小时。 <ol><li>在生存手术应用一致的无菌技术。实施抑制到最大可能的程度上的微生物CON程序污染从而显著感染或化脓不会发生。这些程序包括使用无菌器械和无菌材料，手术区消毒，并去除毛皮/毛过这个网站的手术部位消毒。 </li></ol></li><li>插管的小鼠具有自钝制备20号针头。 <ol><li>把鼠标在仰卧位，头部过伸。 <ol><li>着眼于颈部区域的光。提起用钝pincet舌头。喉部的入口可以清楚地看到。 </li><li>经过喉部的钝针头插入直视下气管。通过鼠标连接到呼吸机评估正确的插管（每搏输出量在微升：3×体重（克）+ 155;频率：每分钟120次）。 </li></ol></li><li>另外，通过先仔细暴露气管增强气管插管的可视化。 <ol><li>做一个5毫米的中颈部切口和缩回肌肉组织只是气管上方。 </li><li>执行使用手术立体的气管直接可视化的气管插管。抬起舌并输入自制备钝化20号针头进入气管。通过鼠标连接到呼吸机确认无误插管（每搏输出量在微升：3×体重（克）+ 155;频率：每分钟120次）。 </li></ol></li></ol></li><li>按住鼠标在仰卧位和修复鼠标用胶带。在加热垫进行手术，以防止体温过低。 <ol><li>刮胡子和消毒用聚维酮碘皮肤。注意使左后肢穿过右后肢，以便在手术过程中获得关于左心室更好的视野。 </li></ol></li><li>使一个小的横向皮肤切口到胸骨并分离下面的皮肤和肌肉。 </li><li>拉米一边。胸小肌和M。胸大肌用5-0丝线缝合。 </li><li>做一个我ncision在第三肋间隙通过插入一个钝pincet。 </li><li>移动下肋间肌从横向的pincet向内侧到胸骨为止。通过从内到皮肤推pincet穿刺胸壁。通过仔细切割肋间肌只是用小剪刀将pincet上面完成开胸手术。使用这种技术，以防止肺部穿刺。 </li><li>把浸渍于0.9％的NaCl的海绵进入空腔，以保护肺部。引入一个伤口吊具（胸牵开器）插入肋间空间，以获得心脏的左侧的曝光。截至目前，左心房，左心室，左冠状动脉前降支是立体显微镜下可见的。 </li><li>执行左冠状动脉前降支约左心房的尖端之下1mm的单个6-0 Prolene线结扎的结扎。这是从第一对角支远侧。 注：另外，7-0（00.05毫米直径）或8-0线程（0.04毫米直径）可被使用。针是C-113毫米3/8圆锥角针。左冠状动脉前降支动脉结扎术成功立即引起变色，导致受影响的领土苍白出现心肌。 </li><li>取出伤口吊具（胸部拉钩）。 <ol><li>将三个6-0的Ti-的Cron缝线周围的肋间。前收紧缝合线，从胸腔除去海绵和通过阻断呼吸机的流出重新展开肺部。通过这样做，肺部重新与壁层胸膜。 </li><li>随后，拉动缝线紧，向下按在胸前重复再扩张。确认使用少量盐水的胸廓的成功关闭（无气泡，必须对胸部施加压力时可以看到的）。 </li><li>期待通过肋间肌，确认肺部正常的扩张。重新定位双方胸大肌肌肉，作为一个额外的障碍预防气胸。 </li></ol></li><li>关闭用5-0丝缝合皮肤。 </li><li>从呼吸机断开鼠标，并允许恢复加热垫。不要让动物无人看管，直到它恢复足够的意识，保持胸骨斜卧。不返回已经历手术给其他动物的公司，直到完全恢复的动物。 </li><li>始终如一地提供术后镇痛（丁丙诺啡0.05毫克/公斤SQ BID至少48小时手术后）。 </li></ol> 2. 在体内创血流动力学测量小鼠<ol><li>在手术前，淹没在无菌水中的1.0法国米勒压力导管在37℃下至少30分钟，以最小化信号漂移。电子校准在0毫米汞柱和100毫米汞柱和记录数据的压力传感器在2000赫兹。 </li><li>由1.4克/公斤氨基甲酸酯腹膜内给药进行麻醉。检查鼠标达到其应有的麻醉平面，当它不再反应的公司脚趾捏。 </li><li>将鼠标麻醉仰卧位。确保其四肢用胶带。保持体温与加热垫和监控与直肠探头。剃颈部区域，使一个中线切口，在颈部区域，以暴露甲状腺。 </li><li>修正了弯针的脖子。 </li><li>拉拨唾液腺和暴露右颈总动脉。迷走神经，它类似于一白线，沿着所述动脉。小心用弯钳从迷走神经分离颈动脉。 </li><li>通过右颈总动脉下一个弯钳将其从其它组织中分离出来。动脉周围除去结缔组织。 </li><li>通过右颈总动脉下的两个6-0丝导线。就顶丝，它被放置在头紧一紧结，并配有科赫尔（远端闭塞结扎）修复。通过PROXI发作丝两次从左至右并用2 kochers（近侧非闭塞性线）固定。 </li><li>保持颈动脉湿润滴加无菌的0.9％NaCl。擦干多余的液体用棉签。 </li><li>使在右颈总动脉中的切口与远侧结扎和近侧非闭塞性导线之间的26号针头。 </li><li>推出压力传感器到动脉。确认没有失血。轻轻的1.0法国米勒压力导管推进并以这样的方式，该导管可以通过锁骨下导线小心通过调整近侧非闭塞性导线。 <ol><li>调整近侧非闭塞丝期间尽量减少失血。不压缩的压力传感器同时推进，因为它是很脆弱的太多了。由于近端线不得堵塞动脉，血管应保持充满血液。 </li></ol></li><li>开始录制的压力信号。动脉压力信号fluctuatES在60的舒张压之间的健康小鼠 - 70毫米汞柱和100的收缩压 - 120毫米汞柱。 </li><li>经由无名动脉并经由主动脉进入左心室直接导管。 120毫米汞柱 - 0毫米汞柱和100之间的心室压力波动。允许导管到左心室内稳定。记录信号进行30分钟至60分钟，这取决于实验的要求。 </li><li>在实验结束后，浸泡在Alconox清洁剂的1％的导管30分钟。洗用Milli-Q水的导管。存储导管在泡沫块。 </li><li>检索作进一步分析录音软件数据。 <ol><li>进行数据分析，考虑一个时间间隔，其中所述压力信号是稳定的。选择感兴趣的记录的数据中的至少10个连续心脏周期。 </li><li>使用LabChart软件版本8.0或类似的分析心脏率，最大收缩期左室压力，最小舒张左ventricular压，等容左心室收缩（DP / dt 最大值 ），等容左心室舒张（DP / DT 分钟 ），舒张末期左心室压力的峰值速率的峰值速率，以及等容左心室的时间常数压降（头）7。 注：舒张末期压力对应于在该时间点立即诱导等容收缩压力骤增之前的压力。 tau蛋白的计算是基于左心室压力配合到一个单指数衰减曲线，表示为P（T）= P 0 E -t / tau蛋白 + B，在该公式中，P（t）是在时刻左心室压力之后DP / dt的的最大负值吨已经达到。参数b对应于理论渐近线，它在一个简化的方法可以假定为零。增强等容舒张导致tau的一个较小的值。 </li></ol></li></OL&gt;

<ol>
	<li>He, 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=Risk+factors+for+congestive+heart+failure+in+US+men+and+women:+NHANES+I+epidemiologic+follow-up+study.">Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.</a> Arch Intern Med. 161, 996-1002 (2001).</li><li>Anversa, P., 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=Ischemic+cardiomyopathy:+pathophysiologic+mechanisms.">Ischemic cardiomyopathy: pathophysiologic mechanisms.</a> Prog Cardiovasc Dis. 33, 49-70 (1990).</li><li>Erlebacher, J. A., Weiss, J. L., Weisfeldt, M. L., Bulkley, 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=Early+dilation+of+the+infarcted+segment+in+acute+transmural+myocardial+infarction:+role+of+infarct+expansion+in+acute+left+ventricular+enlargement.">Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement.</a> J Am Coll Cardiol. 4, 201-208 (1984).</li><li>Shimizu, I., 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=Excessive+cardiac+insulin+signaling+exacerbates+systolic+dysfunction+induced+by+pressure+overload+in+rodents.">Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents.</a> J Clin Invest. 120, 1506-1514 (2010).</li><li>Tirziu, D., 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+hypertrophy+in+the+absence+of+external+stimuli+is+induced+by+angiogenesis+in+mice.">Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice.</a> J Clin Invest. 117, 3188-3197 (2007).</li><li>Theilmeier, 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=High-density+lipoproteins+and+their+constituent,+sphingosine-1-phosphate,+directly+protect+the+heart+against+ischemia/reperfusion+injury+in+vivo+via+the+S1P3+lysophospholipid+receptor.">High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor.</a> Circulation. 114, 1403-1409 (2006).</li><li>Weiss, J. L., Frederiksen, J. W., Weisfeldt, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+determinants+of+the+time-course+of+fall+in+canine+left+ventricular+pressure.">Hemodynamic determinants of the time-course of fall in canine left ventricular pressure.</a> J Clin Invest. 58, 751-760 (1976).</li><li>Bohl, S., 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=Refined+approach+for+quantification+of+in+vivo+ischemia-reperfusion+injury+in+the+mouse+heart.">Refined approach for quantification of in vivo ischemia-reperfusion injury in the mouse heart.</a> Am J Physiol Heart Circ Physiol. 297, 2054-2058 (2009).</li><li>Van Craeyveld, E., Jacobs, F., Gordts, S. C., De Geest, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-density+lipoprotein+receptor+gene+transfer+in+hypercholesterolemic+mice+improves+cardiac+function+after+myocardial+infarction.">Low-density lipoprotein receptor gene transfer in hypercholesterolemic mice improves cardiac function after myocardial infarction.</a> Gene Ther. 19, 860-871 (2012).</li><li>Gordts, S. 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=Beneficial+effects+of+selective+HDL-raising+gene+transfer+on+survival,+cardiac+remodelling+and+cardiac+function+after+myocardial+infarction+in+mice.">Beneficial effects of selective HDL-raising gene transfer on survival, cardiac remodelling and cardiac function after myocardial infarction in mice.</a> Gene Ther. 20, 1053-1061 (2013).</li><li>Junqueira, L. C., Bignolas, G., Brentani, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Picrosirius+staining+plus+polarization+microscopy,+a+specific+method+for+collagen+detection+in+tissue+sections.">Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections.</a> Histochem J. 11, 447-455 (1979).</li><li>Patten, R. D., Hall-Porter, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+animal+models+of+heart+failure:+development+of+novel+therapies,+past+and+present.">Small animal models of heart failure: development of novel therapies, past and present.</a> Circ Heart Fail. 2, 138-144 (2009).</li><li>Zolotareva, A. G., Kogan, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+experimental+occlusive+myocardial+infarction+in+mice.">Production of experimental occlusive myocardial infarction in mice.</a> Cor Vasa. 20, 308-314 (1978).</li><li>Michael, L. 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=Myocardial+ischemia+and+reperfusion:+a+murine+model.">Myocardial ischemia and reperfusion: a murine model.</a> Am J Physiol. 269, 2147-2154 (1995).</li><li>Salto-Tellez, 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=Myocardial+infarction+in+the+C57BL/6J+mouse:+a+quantifiable+and+highly+reproducible+experimental+model.">Myocardial infarction in the C57BL/6J mouse: a quantifiable and highly reproducible experimental model.</a> Cardiovasc Pathol. 13, 91-97 (2004).</li><li>Fernandez, B., 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=The+coronary+arteries+of+the+C57BL/6+mouse+strains:+implications+for+comparison+with+mutant+models.">The coronary arteries of the C57BL/6 mouse strains: implications for comparison with mutant models.</a> J Anat. 212, 12-18 (2008).</li><li>Kumar, D., 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=Distinct+mouse+coronary+anatomy+and+myocardial+infarction+consequent+to+ligation.">Distinct mouse coronary anatomy and myocardial infarction consequent to ligation.</a> Coron Artery Dis. 16, 41-44 (2005).</li><li>Clauss, S. B., Walker, D. L., Kirby, M. L., Schimel, D., Lo, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patterning+of+coronary+arteries+in+wildtype+and+connexin43+knockout+mice.">Patterning of coronary arteries in wildtype and connexin43 knockout mice.</a> Dev Dyn. 235, 2786-2794 (2006).</li><li>Icardo, J. M., Colvee, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Origin+and+course+of+the+coronary+arteries+in+normal+mice+and+in+iv/iv+mice.">Origin and course of the coronary arteries in normal mice and in iv/iv mice.</a> J Anat. 199, 473-482 (2001).</li><li>Yoldas, A., Ozmen, E., Ozdemir, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Macroscopic+description+of+the+coronary+arteries+in+Swiss+albino+mice+(Mus+musculus).">Macroscopic description of the coronary arteries in Swiss albino mice (Mus musculus).</a> J S Afr Vet Assoc. 81, 247-252 (2010).</li><li>James, T. N., Burch, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood+supply+of+the+human+interventricular+septum.">Blood supply of the human interventricular septum.</a> Circulation. 17, 391-396 (1958).</li><li>Gao, X. M., Xu, Q., Kiriazis, H., Dart, A. M., Du, X. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+model+of+post-infarct+ventricular+rupture:+time+course,+strain-+and+gender-dependency,+tensile+strength,+and+histopathology.">Mouse model of post-infarct ventricular rupture: time course, strain- and gender-dependency, tensile strength, and histopathology.</a> Cardiovasc Res. 65, 469-477 (2005).</li><li>Muthuramu, I., Jacobs, F., Singh, N., Gordts, S. C., De Geest, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+homocysteine+lowering+gene+transfer+improves+infarct+healing,+attenuates+remodelling,+and+enhances+diastolic+function+after+myocardial+infarction+in+mice.">Selective homocysteine lowering gene transfer improves infarct healing, attenuates remodelling, and enhances diastolic function after myocardial infarction in mice.</a> PLoS One. 8, 63710 (2013).</li><li>Eaton, L. W., Weiss, J. L., Bulkley, B. H., Garrison, J. B., Weisfeldt, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+cardiac+dilatation+after+acute+myocardial+infarction:+recognition+by+two-dimensional+echocardiography.">Regional cardiac dilatation after acute myocardial infarction: recognition by two-dimensional echocardiography.</a> N Engl J Med. 300, 57-62 (1979).</li><li>Erlebacher, J. 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=Late+effects+of+acute+infarct+dilation+on+heart+size:+a+two+dimensional+echocardiographic+study.">Late effects of acute infarct dilation on heart size: a two dimensional echocardiographic study.</a> Am J Cardiol. 49, 1120-1126 (1982).</li><li>Schuster, E. H., Bulkley, 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=Expansion+of+transmural+myocardial+infarction:+a+pathophysiologic+factor+in+cardiac+rupture.">Expansion of transmural myocardial infarction: a pathophysiologic factor in cardiac rupture.</a> Circulation. 60, 1532-1538 (1979).</li><li>Jugdutt, B. I., Michorowski, B. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+infarct+expansion+in+rupture+of+the+ventricular+septum+after+acute+myocardial+infarction:+a+two-dimensional+echocardiographic+study.">Role of infarct expansion in rupture of the ventricular septum after acute myocardial infarction: a two-dimensional echocardiographic study.</a> Clin Cardiol. 10, 641-652 (1987).</li><li>Pacher, P., Nagayama, T., Mukhopadhyay, P., Batkai, S., Kass, D. A. <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+cardiac+function+using+pressure-volume+conductance+catheter+technique+in+mice+and+rats.">Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.</a> Nat Protoc. 3, 1422-1434 (2008).</li><li>Vanden Bergh, A., Flameng, W., Herijgers, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parameters+of+ventricular+contractility+in+mice:+influence+of+load+and+sensitivity+to+changes+in+inotropic+state.">Parameters of ventricular contractility in mice: influence of load and sensitivity to changes in inotropic state.</a> Pflugers Arch. 455, 987-994 (2008).</li></ol>

None of the authors reports competing financial interests.

在心肌的结构和功能的慢性变化，左心功能不全的发展，并进展到心脏衰竭可以几种鼠模型12进行调查。心脏重塑和功能障碍可以通过心肌损伤可诱发或压力过载继发于横向主动脉缩窄，或可在扩张型心肌病12的遗传模型进行研究。显然，小鼠模型的最显着优点是转基因和基因敲除菌株，包括细胞类型特异性和可诱导的转基因模型中的大量的可用性。评价在这些模型心脏重构的已?...

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with the 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 failure1.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. In other words, ventricular remodelling concerns an alteration of the left ventricular architecture. 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 (e.g., mitral insufficiency). Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure.
Loss of myocardial tissue following acute myocardial infarction results in a decreased systolic ejection and an increased left ventricular end-diastolic volume and pressure. The Frank-Starling mechanism, implying that an increased end-diastolic volume results in an increased pressure developed during systole, may help to restore cardiac output. However, the concomitant increased wall stress may induce regional hypertrophy in the non-infarcted segment, whereas in the infarcted area expansion and thinning may occur. Experimental animal studies show that the infarcted ventricle hypertrophies and that the degree of hypertrophy is dependent on the infarct size2. 
The loss of myocardial tissue following acute myocardial infarction results in a sudden increase in loading conditions. Post-infarct remodelling occurs in the setting of volume overload, since the stretched and dilated infarcted tissue increases the left ventricular volume. An increased ventricular volume not only implies increased preload (passive ventricular wall stress at the end of diastole) but also increased afterload (total myocardial wall stress during systolic ejection). Afterload is increased since the systolic radius is increased. Therefore, ventricular remodelling post-myocardial infarction is characterized by mixed features of volume overload and pressure overload.
The myocardium consists of 3 integrated components: cardiomyocytes, extracellular matrix, and the capillary microcirculation. All 3&#160;components are involved in the remodelling process. Matrix metalloproteinases produced by inflammatory cells induce degradation of intermyocyte collagen struts and cardiomyocyte slippage. This leads to infarct expansion characterized by the disproportionate thinning and dilatation of the infarct segment3. In later stages of remodelling, interstitial fibrosis is induced, which negatively affects the diastolic properties of the heart. 
The vascular and cardiomyocyte compartment in the myocardium should remain balanced in the process of ventricular remodelling to avoid tissue hypoxia4,5. Whether hypertrophy progresses to heart failure or not may be critically dependent on this balance between the vascular and cardiomyocyte compartment in the myocardium. 
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 reperfusion6. In contrast, the infarct area at 24 hours 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.

<table border="0" cellpadding="0" cellspacing="0" width="1061">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Reagents</td>
			<td style="width:223px;"></td>
			<td style="width:123px;"></td>
			<td style="width:495px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Buprenorphine (Buprenex&#174;)</td>
			<td style="width:223px;">Bedford Laboratories</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="52">
			<td height="52" style="height:52px;width:221px;">Sodium Pentobarbital (Nembutal&#174;)</td>
			<td style="width:223px;">Ceva</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="31">
			<td height="31" style="height:31px;width:221px;">Betadine&#174;</td>
			<td style="width:223px;">VWR internationals</td>
			<td>200065-400</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">5 - 0 silk suture</td>
			<td>Ethicon, Johnson &#38; Johnson Medical</td>
			<td>K890H</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">6 - 0 prolene suture&#160;</td>
			<td>Ethicon, Johnson &#38; Johnson Medical</td>
			<td>F1832</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">6 - 0 Ti- Cron suture</td>
			<td>Ethicon, Johnson &#38; Johnson Medical</td>
			<td>F1823</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Urethane&#160;</td>
			<td style="width:223px;">Sigma</td>
			<td>94300</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Alconox</td>
			<td>Alconox Inc.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;"></td>
			<td style="width:223px;"></td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Equipment</td>
			<td style="width:223px;"></td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:221px;">Ventilator, MiniVent Model 845</td>
			<td style="width:223px;">Hugo Sachs</td>
			<td style="width:123px;">73-0043</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:221px;">Chest retractor or Thorax retractor</td>
			<td style="width:223px;">Kent Scientific corporation</td>
			<td style="width:123px;">INS600240</td>
			<td>ALM Self-retaining, serrated, 7cm long, 4 x 4 &#34;L&#34; shaped prongs, 3mm x 3mm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">1.0 French Millar pressure catheter&#160;</td>
			<td style="width:223px;">Millar Instruments&#160;</td>
			<td style="width:123px;">SPR - 1000/NR</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Powerlab</td>
			<td style="width:223px;">ADInstruments Pty Ltd.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">LabChart&#174; software</td>
			<td style="width:223px;">ADInstruments Pty Ltd.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Rectal probe</td>
			<td style="width:223px;">ADInstruments Pty Ltd.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure

心脏衰竭是其中心脏不能泵送血液的速率与在休息或应激期间蜂窝氧气要求相称的综合症。它的特征是液体潴留，气短，和疲劳，特别是在消耗。心脏衰竭是一个日益严重的公共健康问题，住院的主要原因，和死亡的一个主要原因。缺血性心脏疾病是心脏衰竭的主​​要原因。 心室重塑是指改变结构左心室，大小和形状。这种建筑的左心室重塑被损伤（ 例如，心肌梗塞）引起的，通过压力负荷（ 例如，全身性动脉高血压或主动脉瓣狭窄），或按体积超负荷。由于心室重构影响墙体的压力，但对心功能和心脏衰竭的发展产生深远的影响。左前descendin永久性结扎模型克冠状动脉小鼠被用来研究心室重构和心脏功能后​​心肌梗死。该模型是在目标和病理生理学的相关方面相比左前降冠状动脉的瞬态结扎模型根本的不同。在后一种缺血/再灌注损伤模型，梗死的初始程度可以通过影响心肌打捞再灌注因素进行调制。与此相反，在梗塞面积在左前降冠状动脉的永久结扎后24小时，是固定的。在此模型中的心功能会受1）梗塞扩展，梗塞愈合，和瘢痕形成的方法; 2）左心室扩张，心肌肥厚，心室重构伴随发展。 除了左前永久性结扎的下行冠状动脉，浸润性血液动力学MEA的技术中的模型小鼠surements中详细介绍。

心肌梗死的程度可以通过伊文思蓝/ 2,3,5-氯化三苯基四唑（TTC）双重染色来评估。 TTC是氧化还原指示剂，其被转换为深红色-1,3,5- triphenylformazan在活由于NADH 8的存在，各种脱氢酶的活性组织中。 图1示出的心脏的代表性部分中，在24小时后结扎左冠状动脉前降支的。蓝染的区域表示非缺血/正常区域。在危险的心肌区域被定义为灌注从左前降冠状动脉的结扎远侧床内的心肌组织。...

Watch this Scientific Journal Video about Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure at JoVE.com

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

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 ...

permanent-ligation-left-anterior-descending-coronary-artery-mice

Research

JoVE Journal

Medicine

27.5K 次观看.  Catholic University of Leuven. 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.

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

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling. 
Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy. 
Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed. 
Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical.

Numerous genetic manipulations and/or intramyocardial injections of genes, proteins, cells, and/or biomaterials are superimposed upon the dimension of time in studies of acute ischemia/ reperfusion injury and chronic remodeling in mice. This video illustrates the microsurgical procedures for ischemia/reperfusion, permanent coronary artery ligation, and intramyocardial injection studies.

结扎冠状动脉内注射在小鼠模型梗死

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo.  With the advent of genetic modifications to ...

科研

医学

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques include transient or permanent, focal or global ischemia models using many different animal models, with the most common being rodents.
The permanent MCA ligation method which is also referred as pMCAo in the literature is used extensively as a focal ischemia model in rodents 1-6. This method was originally described for rats by Tamura et al. in 1981 7. In this protocol a craniotomy was used to access the MCA and the proximal regions were occluded by electrocoagulation. The infarcts involve mostly cortical and sometimes striatal regions depending on the location of the occlusion. This technique is now well established and used in many laboratories 8-13. Early use of this technique led to the definition and description of &#x201C;infarct core&#x201D; and &#x201C;penumbra&#x201D; 14-16, and it is often used to evaluate potential neuroprotective compounds 10, 12, 13, 17. Although the initial studies were performed in rats, permanent MCA ligation has been used successfully in mice with slight modifications 18-20 .
This model yields reproducible infarcts and increased post-survival rates. Approximately 80% of the ischemic strokes in humans happen in the MCA area 21 and thus this is a very relevant model for stroke studies. Currently, there is a paucity of effective treatments available to stroke patients, and thus there is a need for good models to test potential pharmacological compounds and evaluate physiological outcomes. This method can also be used for studying intracellular hypoxia response mechanisms in vivo. 
Here, we present the MCA ligation surgery in a C57/BL6 mouse. We describe the pre-surgical preparation, MCA ligation surgery and 2,3,5 Triphenyltetrazolium chloride (TTC) staining for quantification of infarct volumes.

Middle cerebral artery (MCA) ligation is a technique to study focal cerebral ischemia in animal models. In this method, the middle cerebral artery is exposed by craniotomy and ligated by cauterization. This method gives highly reproducible infarct volumes and increased post-operative survival rates compared to other methods available.

在小鼠永久性大脑中动脉结扎术中的应用

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to ...

Modified Technique for Coronary Artery Ligation in Mice

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI we need better knowledge about pathophysiology of myocardial ischemia. This knowledge may be valuable to define new therapeutic targets for innovative cardiovascular therapies4. Experimental MI model in mice is an increasingly popular small-animal model in preclinical research in which MI is induced by means of permanent or temporary ligation of left coronary artery (LCA)5. In this video, we describe the step-by-step method of how to induce experimental MI in mice.
The animal is first anesthetized with 2% isoflurane. The unconscious mouse is then intubated and connected to a ventilator for artificial ventilation. The left chest is shaved and 1.5 cm incision along mid-axillary line is made in the skin. The left pectoralis major muscle is bluntly dissociated until the ribs are exposed. The muscle layers are pulled aside and fixed with an eyelid-retractor. After these preparations, left thoracotomy is performed between the third and fourth ribs in order to visualize the anterior surface of the heart and left lung. The proximal segment of LCA artery is then ligated with a 7-0 ethilon suture which typically induces an infarct size ~40% of left ventricle. At the end, the chest is closed and the animals receive postoperative analgesia (Temgesic, 0.3 mg/50 ml, ip). The animals are kept in a warm cage until spontaneous recovery.

The surgical procedure used to induce experimental myocardial infarction in mice begins with left thoracotomy between the third and the fourth ribs in order to visualize the anterior surface of the heart and left lung. The left coronary artery is ligated, the chest is closed and the mouse is allowed to recover spontaneously.

改性技术在小鼠冠状动脉结扎

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI ...

A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms at work during MI and developing effective therapeutic approaches requires methodology to reproducibly simulate the clinical incidence and reflect the pathophysiological changes associated with MI. Here, we describe a surgical method to induce MI in mouse models that can be used for short-term ischemia-reperfusion (I/R) injury as well as permanent ligation. The major advantage of this method is to facilitate location of the left anterior descending artery (LAD) to allow for accurate ligation of this artery to induce ischemia in the left ventricle of the mouse heart. Accurate positioning of the ligature on the LAD increases reproducibility of infarct size and thus produces more reliable results. Greater precision in placement of the ligature will improve the standard surgical approaches to simulate MI in mice, thus reducing the number of experimental animals necessary for statistically relevant studies and improving our understanding of the mechanisms producing cardiac dysfunction following MI. This mouse model of MI is also useful for the preclinical testing of treatments targeting myocardial damage following MI.

We introduce a surgical method to induce experimental ischemia/reperfusion (I/R) injury to simulate myocardial infarction (MI) in mouse models that allows for more clarity in positioning of the ligation on the left anterior descending artery (LAD) to increase the reproducibility of MI experiments in mice.

心肌缺血再灌注损伤的通过左前降支结扎小鼠模型

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by reduced blood supply to the heart, resulting in the loss of oxygen to and the ensuing necrosis of the heart muscle. The MI model has gained popularity for its use as a short-term ischemia-reperfusion model and a long-term permanent ligation model. Below, we describe a reliable method for the permanent ligation of the LAD. With mouse genetic engineering technology becoming more advanced, and with an increasing availability of quality murine surgical instruments, the mouse has become a popular model for MI surgeries. Our surgical model incorporates the use of an easily reversible anesthetic for the rapid recovery of the mouse; a minimally invasive endotracheal intubation without involving a tracheotomy; and a thoracentesis through the original thoracotomy site without creating an additional incision in the chest, as is done in some other methods, to effectively remove excess blood and air from the chest cavity. This method is comparatively less invasive than other methods, which dramatically reduces surgical and post-surgical complications and mortality and improves reproducibility.

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

We provide a reliable method for left anterior descending artery (LAD) ligation in a mouse model. This method is comparatively less invasive than other methods, involving endotracheal intubation, a left-sided thoracotomy approach, and thoracentesis. This method can be used as a model for both acute and chronic myocardial infarction (MI).

鼠左前降支（LAD）冠状动脉结扎：改进和简化模型的心肌梗死

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ischemia and infarction in children. If left untreated, it results in a 90% mortality rate in the first year of life. In patients who survive to the adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow provide a substrate for chronic subendocardial ischemia, which may lead to left ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular arrhythmias, and sudden cardiac death. The average age of life-threatening presentation is 33 years and of sudden cardiac death 31 years. Therefore, surgical correction is highly recommended as soon as the diagnosis is made, regardless of age. In adult-type ALCAPA originating from the right-facing sinus of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is the more physiologically sound repair technique to re-establish the dual-coronary perfusion system and is recommended. This protocol describes the technique of direct re-implantation of adult-type ALCAPA into the aorta.

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

Surgical correction of ALCAPA is highly recommended, regardless of age or the degree of intercoronary collateralization. This protocol presents a technique for the direct re-implantation of adult-type ALCAPA into the aorta to re-establish the dual-coronary perfusion. Whenever feasible, direct re-implantation is preferred to other surgical correction techniques.

左冠状动脉直接再注入与从肺动脉左冠状动脉起源异常成人主动脉（ALCAPA）

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

使用左前部降冠动脉的永久结扎的月心肌梗死模型

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

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

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major causes of mortality and morbidity around the world. Cell-based therapies for cardiac repair and improvement of left ventricular function after MI have attracted considerable attention. Accordingly, the safety and efficacy of these cell transplantations should be tested in a preclinical large animal model of HF prior to clinical use. Pigs are widely used for cardiovascular disease research due to their similarity to humans in terms of heart size and coronary anatomy. Therefore, we sought to present an effective protocol for the establishment of a porcine chronic HF model using closed-chest coronary balloon occlusion of the left circumflex artery (LCX), followed by rapid ventricular pacing induced with pacemaker implantation. Eight weeks later, the stem cells were administered by intramyocardial injection in the peri-infarct area. Then the infarct size, cell survival, and left ventricular function (including echocardiography, hemodynamic parameters, and electrophysiology) were evaluated. This study helps establish a stable preclinical large animal HF model for stem cell treatment.

We sought to establish a swine model of heart failure induced by left circumflex artery blockage and rapid pacing to test the effect and safety of intramyocardial administration of stem cells for cell-based therapies.

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 ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.
Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult G&#246;ttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model.
MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in G&#246;ttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in G&#246;ttingen minipigs and at 2 months in Landrace pigs, respectively.
Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in G&#246;ttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, G&#246;ttingen minipigs showed a slight increase in LVED mass only at 6 months.
In summary, this is the first characterization of post-MI HF in G&#246;ttingen minipigs in comparison to Landrace pigs, showing that the G&#246;ttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the G&#246;ttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&amp;#246;ttingen Minipigs and Landrace Pigs

The overall goal of the current study is to present the techniques of induction of myocardial infarction (MI) and post-myocardial infarction heart failure (post-MI HF) in closed-chest, adult G&#246;ttingen minipigs and the characterization of post-MI HF model in G&#246;ttingen minipigs as compared to Landrace pigs.

封闭胸冠状动脉闭塞/输液模型中的心肌梗塞后心力衰竭

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

There are several differences between the right and left ventricles. However, the pathophysiology of right ventricular infarction (RVI) has not been clarified. In the present protocol, a reproducible method for RVI mouse model generation is introduced, which may provide a means to explain the mechanism of RVI.

小鼠右冠状动脉永久结扎诱导的右心室性心肌梗死的生成与表征

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...