Name: establishing a swine model of post-myocardial infarction heart failure for stem cell treatment
Uploaded: 2020-05-25T14:00:00
Description: Watch this Scientific Journal Video about Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment at JoVE.com

作者感谢阿尔弗雷达和孔德忠在动物实验中的出色技术支持。

所有动物实验都按照美国国家卫生研究院和香港大学法规所公布的《实验室动物护理和使用指南》进行，该议定书已获香港大学活动物教学及研究使用委员会（CULTAR）批准。
注：本研究使用体重35-40公斤（9-12个月大）的雌性农场猪。此实验的流程图如图 1 所示。
1. 外科手术
<ol><li>动物的麻醉和准备<ol>
<li>禁食动物12小时，在实验?...

<ol>
	<li>Mozaffarian, 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=Heart+disease+and+stroke+statistics-2015+update:+a+report+from+the+American+Heart+Association.">Heart disease and stroke statistics-2015 update: a report from the American Heart Association.</a> Circulation. 131, e29 (2015).</li><li>Hospital Authority. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Hospital Authority Statistical Report 2013. , (2013).</li><li>Cung, T. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cyclosporine+before+PCI+in+Patients+with+Acute+Myocardial+Infarction.">Cyclosporine before PCI in Patients with Acute Myocardial Infarction.</a> The New England Journal of Medicine. 373 (11), 1021-1031 (2015).</li><li>Liao, S. Y., 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=Proarrhythmic+risk+of+embryonic+stem+cell-derived+cardiomyocyte+transplantation+in+infarcted+myocardium.">Proarrhythmic risk of embryonic stem cell-derived cardiomyocyte transplantation in infarcted myocardium.</a> Heart Rhythm. 7, 1852-1859 (2010).</li><li>Liao, S. Y., 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=Overexpression+of+Kir2.1+channel+in+embryonic+stem+cell-derived+cardiomyocytes+attenuates+posttransplantation+proarrhythmic+risk+in+myocardial+infarction.">Overexpression of Kir2.1 channel in embryonic stem cell-derived cardiomyocytes attenuates posttransplantation proarrhythmic risk in myocardial infarction.</a> Heart Rhythm. 10, 273-282 (2013).</li><li>Liu, Y., 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=Thoracic+spinal+cord+stimulation+improves+cardiac+contractile+function+and+myocardial+oxygen+consumption+in+a+porcine+model+of+ischemic+heart+failure.">Thoracic spinal cord stimulation improves cardiac contractile function and myocardial oxygen consumption in a porcine model of ischemic heart failure.</a> Journal of Cardiovascular Electrophysiology. 23, 534-540 (2012).</li><li>Liao, S. Y., 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=Improvement+of+Myocardial+Function+Following+Catheter-Based+Renal+Denervation+in+Heart+Failure.">Improvement of Myocardial Function Following Catheter-Based Renal Denervation in Heart Failure.</a> JACC: Basic to Translational Science. 2 (3), 270-281 (2017).</li><li>Liao, S. Y., 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=Remodelling+of+cardiac+sympathetic+re-innervation+with+thoracic+spinal+cord+stimulation+improves+left+ventricular+function+in+a+porcine+model+of+heart+failure.">Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.</a> Europace. 17 (12), 1875-1883 (2015).</li><li>Daehnert, I., Rotzsch, C., Wiener, M., Schneider, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+right+ventricular+pacing+is+an+alternative+to+adenosine+in+catheter+interventional+procedures+for+congenital+heart+disease.">Rapid right ventricular pacing is an alternative to adenosine in catheter interventional procedures for congenital heart disease.</a> Heart. 90 (9), 1047-1050 (2004).</li><li>H&#225;la, P., 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=Tachycardia-Induced+Cardiomyopathy+as+a+Chronic+Heart+Failure+Model+in+Swine.">Tachycardia-Induced Cardiomyopathy as a Chronic Heart Failure Model in Swine.</a> Journal of Visualized Experiments. (132), e57030 (2018).</li><li>Santoso, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endomyocardial+implantation+of+autologous+bone+marrow+mononuclear+cells+in+advanced+ischemic+heart+failure:+a+randomized+placebo-controlled+trial+(END-HF).">Endomyocardial implantation of autologous bone marrow mononuclear cells in advanced ischemic heart failure: a randomized placebo-controlled trial (END-HF).</a> Journal of Cardiovascular Translational Research. 7, 545-552 (2014).</li><li>Traverse, J. 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=Cardiovascular+Cell+Therapy+Research+Network.+Effect+of+intracoronary+delivery+of+autologous+bone+marrow+mononuclear+cells+2+to+3+weeks+following+acute+myocardial+infarction+on+left+ventricular+function:+the+LateTIME+randomized+trial.">Cardiovascular Cell Therapy Research Network. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial.</a> Journal of the American Medical Association. 306, 2110-2119 (2011).</li><li>Traverse, J. 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=Cardiovascular+Cell+Therapy+Research+Network+(CCTRN).+Effect+of+the+use+and+timing+of+bone+marrow+mononuclear+cell+delivery+on+left+ventricular+function+after+acute+myocardial+infarction:+the+TIME+randomized+trial.">Cardiovascular Cell Therapy Research Network (CCTRN). Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.</a> Journal of the American Medical Association. 308, 2380-2389 (2012).</li><li>de Jong, R., Houtgraaf, J. H., Samiei, S., Boersma, E., Duckers, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracoronary+stem+cell+infusion+after+myocardial+infarction.+A+meta-analysis+and+update+on+clinical+trials.">Intracoronary stem cell infusion after myocardial infarction. A meta-analysis and update on clinical trials.</a> Circulation: Cardiovascular Interventions. 7, 156-167 (2014).</li><li>Nowbar, A. N., 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=DAMASCENE+writing+group.+Discrepancies+in+autologous+bone+marrow+stem+cell+trials+and+enhancement+of+ejection+fraction+(DAMASCENE):+weighted+regression+and+meta-analysis.">DAMASCENE writing group. Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis.</a> British Medical Journal. 348, g2688 (2014).</li><li>Kanelidis, A. J., Premer, C., Lopez, J., Balkan, W., Hare, 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=Route+of+Delivery+Modulates+the+Efficacy+of+Mesenchymal+Stem+Cell+Therapy+for+Myocardial+Infarction:+A+Meta-Analysis+of+Preclinical+Studies+and+Clinical+Trials.">Route of Delivery Modulates the Efficacy of Mesenchymal Stem Cell Therapy for Myocardial Infarction: A Meta-Analysis of Preclinical Studies and Clinical Trials.</a> Circulation Research. 120 (7), 1139-1150 (2017).</li><li>Hou, 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=Radiolabeled+cell+distribution+after+intramyocardial,+intracoronary,+and+interstitial+retrograde+coronary+venous+delivery:+implications+for+current+clinical+trials.">Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials.</a> Circulation. 112 (9 Suppl), I150-I156 (2005).</li><li>Hu, X., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Large-Scale+Investigation+of+Hypoxia-Preconditioned+Allogeneic+Mesenchymal+Stem+Cells+for+Myocardial+Repair+in+Nonhuman+Primates:+Paracrine+Activity+Without+Remuscularization.">A Large-Scale Investigation of Hypoxia-Preconditioned Allogeneic Mesenchymal Stem Cells for Myocardial Repair in Nonhuman Primates: Paracrine Activity Without Remuscularization.</a> Circulation Research. 118, 970-983 (2016).</li><li>Chong, J. 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=Human+embryonic-stem-cell-derived+cardiomyocytes+regenerate+non-human+primate+hearts.">Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.</a> Nature. 510, 273-277 (2014).</li><li>Martens, 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=Substantial+early+loss+of+induced+pluripotent+stem+cells+following+transplantation+in+myocardial+infarction.">Substantial early loss of induced pluripotent stem cells following transplantation in myocardial infarction.</a> Artificial Organs. 38, 978-984 (2014).</li><li>Shiba, Y., 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=Allogeneic+transplantation+of+iPS+cell-derived+cardiomyocytes+regenerates+primate+hearts.">Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.</a> Nature. 538, 388-391 (2016).</li></ol>

标准动物模型对于了解疾病的病理生理学和机制以及测试新的治疗方法至关重要。我们的协议建立了由左环状动脉阻塞和快速起搏诱导的HF猪模型。在MI诱导八周后，这些动物对LVEF、LVEDD、LVESD、+dP/dt和ESPVR有显著损伤。该协议还测试了干细胞治疗的真菌方法，通过心内注射促进心脏再生。评估梗塞大小以及心脏收缩和舒张功能。本研究有助于建立一个稳定且可重复的临床前大型动物HF模型，用于干...

心血管疾病，特别是冠状动脉疾病，仍然是香港及全球1月1日发病和死亡的主要原因。在香港，由2012至2017年，在医院管理局接受治疗的CAD病人人数预计增加26%。在所有病症中，急性心肌梗塞 （MI） 是导致死亡和随后的并发症（如心力衰竭 （HF））的主要原因。这些都带来了巨大的医疗、社会和财政负担。在 MI 患者中，血栓整流治疗或初级皮下冠状动脉干预 （PCI） 是保护生命的有效疗法，但这些疗法只能减少 MI 期间心肌细胞 （CM） 损失。可用的治疗方法无法补充CMs的永久性损失，导致心脏纤维化、心肌重塑、心律失常，并最终心力衰竭。MI后1年的死亡率约为7%，超过20%的患者患有HF3。在末期HF患者中，心脏移植是唯一可用的有效疗法，但受可用器官短缺的有限。新颖的疗法是扭转后MIHF的发展所必需的。因此，基于细胞的治疗被认为是一种有吸引力的方法，以修复受损的CMs和改善左心室（LV）功能在HF后MI。我们先前的研究发现，在MI4、5,的小动物模型中直接进行心肌移植后，干细胞移植对心脏功能的改善是有益的。因此，需要标准化的临床前大型动物HF方案，以进一步测试干细胞移植在临床使用前的有效性和安全性。
近几十年来，猪在心血管研究中的广泛使用，用于干细胞治疗。HF猪是一个很有前途的转化研究模式，由于其在心脏大小、体重、节律、功能和冠状动脉解剖方面与人类相似。此外，猪HF模型可以模仿后MIHF患者在CM代谢，电生理特性，神经内分泌变化在缺血条件下6。此处提出的协议使用这种标准化的猪HF模型，采用左环状动脉（LCX）的闭胸冠状气球闭塞，随后由心脏起搏器植入诱导的快速起搏。该研究还优化了干细胞在心肌内注射的路径，用于治疗后MI HF。其目的是制作慢性心肌梗塞的猪动物模型，可用于开发与严重 CAD 患者临床相关的治疗方法。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
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		<tr>
			<td>Amiodarone</td>
			<td>Mylan</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Anaesthetic machines and respirator</td>
			<td>Drager</td>
			<td>Fabius plus XL</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Angiocath</td>
			<td>Becton Dickinson</td>
			<td>381147</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Anti-human nuclear antigen</td>
			<td>abcam</td>
			<td>ab19118</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Axio Plus image capturing system</td>
			<td>Zeiss</td>
			<td>Axioskop 2 PLUS</td>
			<td>Axioskop 2 plus</td>
		</tr>
		<tr>
			<td>AxioVision Rel. 4.5 software</td>
			<td>Zeiss</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Baytril</td>
			<td>Bayer</td>
			<td>-</td>
			<td>enrofloxacin</td>
		</tr>
		<tr>
			<td>Betadine</td>
			<td>Mundipharma</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>CardioLab Electrophysiology Recording Systems</td>
			<td>GE Healthcare</td>
			<td>G220f</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Culture media</td>
			<td>MesenCult</td>
			<td>05420</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Cyclosporine</td>
			<td>Novartis</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Defibrillator</td>
			<td>GE Healthcare</td>
			<td>CardioServ</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Dorminal</td>
			<td>TEVA</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Echocardiographic system</td>
			<td>GE Vingmed</td>
			<td>Vivid i</td>
			<td>-</td>
		</tr>
		<tr>
			<td>EchoPac software</td>
			<td>GE Vingmed</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Electrophysiological catheter</td>
			<td>Cordis Corp</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Embozene Microsphere</td>
			<td>Boston Scientific</td>
			<td>17020-S1</td>
			<td>700 &#956;m</td>
		</tr>
		<tr>
			<td>Endotracheal tube</td>
			<td>Vet Care</td>
			<td>VCPET70PCW</td>
			<td>Size 7</td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>VWR chemicals</td>
			<td>20821.33</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Formalin</td>
			<td>Sigma</td>
			<td>HT501320</td>
			<td>10%</td>
		</tr>
		<tr>
			<td>IVC balloon Dilatation Catheter</td>
			<td>Boston Scientific</td>
			<td>3917112041</td>
			<td>Mustang</td>
		</tr>
		<tr>
			<td>JR4 guiding catheter</td>
			<td>Cordis Corp</td>
			<td>67208200</td>
			<td>6F</td>
		</tr>
		<tr>
			<td>Lidocaine</td>
			<td>Quala</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Mersilk</td>
			<td>Ethicon</td>
			<td>W584</td>
			<td>2-0</td>
		</tr>
		<tr>
			<td>Metoprolol succinate</td>
			<td>Wockhardt</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Microtome</td>
			<td>Leica</td>
			<td>RM2125RT</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Mobile C arm fluoroscopy equipment</td>
			<td>GE Healthcare</td>
			<td>OEC 9900 Elite</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Pacemaker</td>
			<td>St Jude Medical</td>
			<td>PM1272</td>
			<td>Assurity MRI pacemaker</td>
		</tr>
		<tr>
			<td>Pacemaker generator</td>
			<td>St Jude Medical</td>
			<td>Merlln model 3330</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Pressure-volume catheter</td>
			<td>CD Leycom</td>
			<td>CA-71103-PL</td>
			<td>7F</td>
		</tr>
		<tr>
			<td>Pressure&#8211;volume signal processor</td>
			<td>CD Leycom</td>
			<td>SIGMA-M</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Programmable Stimulator</td>
			<td>Medtronic Inc</td>
			<td>5328</td>
			<td>-</td>
		</tr>
		<tr>
			<td>PTCA Dilatation balloon Catheter</td>
			<td>Boston Scientific</td>
			<td>H7493919120250</td>
			<td>MAVERICK over the wire</td>
		</tr>
		<tr>
			<td>Ramipril</td>
			<td>TEVA</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Sheath introducer</td>
			<td>Cordis Corp</td>
			<td>504608X</td>
			<td>8F, 9F, 12F</td>
		</tr>
		<tr>
			<td>Steroid</td>
			<td>Versus Arthritis</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Temgesic</td>
			<td>Nindivior</td>
			<td>-</td>
			<td>buprenorphine</td>
		</tr>
		<tr>
			<td>Venous indwelling needle</td>
			<td>TERUMO</td>
			<td>SR+OX2225C</td>
			<td>22G</td>
		</tr>
		<tr>
			<td>Vicryl</td>
			<td>Ethicon</td>
			<td>VCP320H</td>
			<td>2-0</td>
		</tr>
		<tr>
			<td>Xylazine</td>
			<td>Alfasan International B.V.</td>
			<td>-</td>
			<td>-</td>
		</tr>
		<tr>
			<td>Zoletil</td>
			<td>Virbac New Zealand Limited</td>
			<td>-</td>
			<td>tiletamine+zolezepam</td>
		</tr>
	</tbody>
</table>

establishing a swine model of post-myocardial infarction heart failure for stem cell treatment

虽然在心肌梗塞（MI）后心力衰竭的治疗方面已取得进步，但MI后HF仍然是全世界死亡和发病的主要原因之一。MI后心脏修复和改善左心室功能的细胞疗法引起了相当大的关注。因此，这些细胞移植的安全性和有效性应在临床使用前在HF的临床前大型动物模型中进行测试。猪由于在心脏大小和冠状动脉解剖学方面与人类相似，被广泛用于心血管疾病研究。因此，我们寻求提出一个有效的方案，建立一个猪慢性HF模型使用封闭胸冠状动脉闭塞的左环弹性动脉（LCX），其次是快速心室起搏诱导与心脏起搏器植入。八周后，干细胞通过心肌注射在近腹区施用。然后评估梗塞大小、细胞存活率和左心室功能（包括心电图、血流动力学参数和电生理学）。本研究有助于建立一个稳定的临床前大型动物HF模型的干细胞治疗。

死亡率 这项研究共使用了24头猪。其中三人在 MI 诱导期间因持续 Vt 死亡。一只动物因伤口出血在开胃手术中因细胞注射而死亡。两只动物因严重感染死亡。由于 EF 的轻微减少（LVEF 减少 > 基线的 40%），两种动物被排除在外。结果，16只动物完成了整个研究方案。
心脏功能和重塑 串行超声心动图?...

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

我们寻求建立一个猪模型的心力衰竭引起的左环弹性动脉阻塞和快速起搏，以测试心肌内给给干细胞的效果和安全性的细胞为基础的疗法。

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 ...

这种猪心脏衰竭模型，由左环状动脉阻塞和快速起搏引起的，可用于评估直接心肌内干细胞注射对心脏再生的影响。我们的猪群心力衰竭模型相当稳定。该模型的新梗塞尺寸约为左心室的 16%，左心室注射梗塞从基线至少减少 40%。将实验猪固定在超生位置，在胡萝卜三角中定位右胡萝卜动脉和杂耍静脉，并使用止血钳和无菌技术分离右胡萝卜动脉和血管。将右胡萝卜动脉和杂耍静脉的端部拉开，并使用血管瘤来调节右杂耍静脉。在 X 射线指导下将心脏起搏器铅插入右心室后，使用钳子分离胸肌和前部骨质肌，并将心脏起搏器连接到铅。然后在两块肌肉之间植入心脏起搏器。然后用 2 - 0 的丝绸关闭两块肌肉。要评估左心室功能的变化，请隔离股骨三角形中的右股动脉和股骨静脉，并计算右股动脉与血管瘤。通过血管将导线放入股骨静脉，取出血管。在导线的指导下，将 12 个法国护套插入股骨静脉并拆下导丝。可以用九个法国护套来调节右股动脉，正如刚刚证明的。并在 X 射线指导下，通过 12 个法国护套插入气球导管进入内部 Vena cava。使用压力体积信号处理器在同位素盐水中校准 7 个法国压力体积导管，并在 X 射线指导下通过 9 个法国护套将导管插入左心室顶点。暂停通风并使用压力体积信号处理器测量左心室最大和负压导数，以及收缩压力和结束舒张压力。然后重新启动通风。对于心肌梗塞诱导，在计算右心肌动脉与八个法国护套之前，在计算右心肌动脉之前，在一小时内静脉注射5毫克每公斤阿米奥达龙和每公斤1.5毫克利多卡因玻利瓦尔，以防止心室心律失常。通过六根法国护套进行冠状动脉造影，通过标准 C 臂荧光镜引导的放置护套进行。在X射线指导下，左环状冠状动脉向第一个迟钝边缘分支闭塞，皮下透骨血管成形术扩张气球导管膨胀。将1毫升700微米的海绵微球与7毫升的 iohexol 混合在10毫升注射器中，然后通过气球导管注射混合物，以阻止左环状冠状动脉。然后放气气球，并执行造影检查以确认遮挡。梗死诱导负荷8周后，将两次10至第八个人类诱导多能干细胞衍生的中流体干细胞在两毫升正常盐水中放入5毫升注射器中，并在麻醉实验动物的顶点节拍区域周围消毒10厘米。使用缩回器在四到五个间空间进行左胸切除术，并进行心内切除术以暴露梗死的横向壁。当非法区域可见时，每次注射进行5至8次心肌注射，注射约300微升细胞，然后用铁丝关闭间空间，用2-0丝线关闭肌肉层，用2-0维丽线关闭皮下组织和皮肤层。为了评估细胞治疗后心室性，通过股骨静脉将六个法国电生理导管插入右心室顶点，并在电生理记录系统中以200毫米/秒的速度显示心内记录，并显示表面心电图leas I、II和III。使用刺激器以两倍于舒张阈值的两毫秒脉冲宽度提供，并在一个 200 毫秒和一个 300 毫秒的驱动周期长度下提供八个刺激的起搏列车，然后是一两个过早的额外刺激。然后按顺序缩短耦合间隔，直到心室有效耐火性心律失常周期被诱导，注意到存在一种不可诱导的持续心室性心律失常。在这个具有代表性的实验中，连续超声心动图检查表明，左心室弹射分数从基线显著减少，而左心室末舒张维度和末体收缩量在心肌梗塞诱导后八周内显著增加。相比之下，左心室弹射分数显著增加，细胞移植组的末收缩量在给给后八周显著下降。负压导数和末收缩压体积关系在心肌梗塞诱导后八周内从基线显著下降，而心肌内肌细胞干细胞的内向作用导致这些功能增加。从每只动物的五到七个连续一厘米厚的部位测量左心室内壁厚度，发现左心室梗塞的百分比约为16% 移植后8周的注射部位周围没有细胞存活。但是，在近脑外区域可以看到少量幸存的注射干细胞。在有心力衰竭的动物中，可引致持续心室性心律失常的事故很容易增加。值得注意的是，干细胞移植没有显著改变基础心肌底，以减少心室性。心室性大出血症。由于左环弯曲冠状动脉阻塞可能诱发心律失常。请务必监测心电图，并立即使用外部双相除颤器，以重建鼻窦。该方法为测试干细胞疗法的疗效提供了稳定且可重复的临床相关大型心力衰竭动物模型。

Research

JoVE Journal

Medicine

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

主动脉原位移植大鼠模型，研究慢性血管病变的发展

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

科研

医学

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 ...

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

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 ...

Vein Interposition Model: A Suitable Model to Study Bypass Graft Patency

静脉介入型号：研究旁路移植通畅一个合适的模型

Bypass grafting is an established treatment method for coronary artery disease. Graft patency continues to be the Achilles heel of saphenous vein grafts. ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

应用 Ameroid 的猪慢性心肌缺血模型

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but ...

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

心动过速诱发的心肌病作为猪慢性心力衰竭模型的研究

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

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

代谢综合征心力衰竭模型大鼠心房心肌细胞的分离与保留射血分数的关系

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

A Cryoinjury Model to Study Myocardial Infarction in the Mouse

研究小鼠心肌梗死的低温损伤模型

The use of animal models is essential for developing new therapeutic strategies for acute coronary syndrome and its complications. In this article, we ...

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

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in GÃƒÆ’Ã‚Â¶ttingen Minipigs and 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 ...

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

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