Name: myocardial infarction by percutaneous embolization coil deployment in a swine model
Uploaded: 2021-11-04T13:00:00
Description: Watch this Scientific Journal Video about Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model at JoVE.com

We express our gratitude to the Center of Comparative Medicine and Bioimaging of Catalonia (CMCiB) and staff for their contribution to the animal model execution. This work was supported by the Instituto de Salud Carlos III (PI18/01227, PI18/00256, INT20/00052), the Sociedad Espa&#241;ola de Cardiolog&#237;a, and the Generalitat de Catalunya [2017-SGR-483]. This work was also funded by the Red de Terapia Celular - TerCel [RD16/0011/0006] and CIBER Cardiovascular [CB16/11/00403] projects, as part of the Plan Nacional de I+D+I, and cofunded by the ISCIII-Subdirecci&#243;n General de Evaluaci&#243;n y el Fondo Europeo de Desarrollo Regional (FEDER). Dr. Fadeuilhe was supported by a grant from the Spanish Society of Cardiology (Madrid, Spain).

This study was approved by the Animal Experimentation Unit Ethical Committee of the Germans Trias i Pujol Health Research Institute (IGTP) and Government Authorities (Generalitat de Catalunya; Code: 10558 and 11208), and complies with all guidelines concerning the use of animals in research and teaching as defined by the Guide for the Care and Use of Laboratory Animals25.
1.&#65279; Preprocedural preparation of animals
<ol>
	<li>Use crossbred Landrace...

<ol>
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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adverse+remodeling+and+reverse+remodeling+after+myocardial+infarction.">Adverse remodeling and reverse remodeling after myocardial infarction.</a> Current Cardiology Reports. 19 (8), 71 (2017).</li><li>Verma, 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=Prognostic+implications+of+left+ventricular+mass+and+geometry+following+myocardial+infarction:+The+VALIANT+(VALsartan+In+Acute+myocardial+iNfarcTion)+echocardiographic+study.">Prognostic implications of left ventricular mass and geometry following myocardial infarction: The VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study.</a> JACC: Cardiovascular Imaging. 1 (5), 582-591 (2008).</li><li>Konstam, M., Kramer, D., Patel, A., Maron, M., Udelson, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Left+ventricular+remodeling+in+heart+failure:+current+concepts+in+clinical+significance+and+assessment.">Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment.</a> JACC. Cardiovascular Imaging. 4 (1), 98-108 (2011).</li><li>Srikanth, G., Prakash, P., Tripathy, N., Dikshit, M., Nityanand, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+a+rat+model+of+myocardial+infarction+with+a+high+survival+rate:+A+suitable+model+for+evaluation+of+efficacy+of+stem+cell+therapy.">Establishment of a rat model of myocardial infarction with a high survival rate: A suitable model for evaluation of efficacy of stem cell therapy.</a> Journal of Stem Cells and Regenerative Medicine. 5 (1), 30 (2009).</li><li>Wu, Y., Yin, X., Wijaya, C., Huang, M. -. H., McConnell, B. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+myocardial+infarction+in+rats.">Acute myocardial infarction in rats.</a> Journal of Visualized Experiments: JoVE. 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C., Post, M., Simons, M., Annex, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Translational+physiology:+porcine+models+of+human+coronary+artery+disease:+implications+for+pre-clinical+trials+of+therapeutic+angiogenesis.">Translational physiology: porcine models of human coronary artery disease: implications for pre-clinical trials of therapeutic angiogenesis.</a> Journal of Applied Physiology. 94 (5), 1689-1701 (2003).</li><li>Tsang, H. 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=Large+animal+models+of+cardiovascular+disease.">Large animal models of cardiovascular disease.</a> Cell Biochemistry and Function. 34 (3), 113 (2016).</li><li>Dixon, J. A., Spinale, F. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Large+animal+models+of+heart+failure.">Large animal models of heart failure.</a> Circulation: Heart Failure. 2 (3), 262-271 (2009).</li><li>G&#225;lvez-Mont&#243;n, 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=Transposition+of+a+pericardial-derived+vascular+adipose+flap+for+myocardial+salvage+after+infarct.">Transposition of a pericardial-derived vascular adipose flap for myocardial salvage after infarct.</a> Cardiovascular Research. 91 (4), 659-667 (2011).</li><li>G&#225;lvez-Mont&#243;n, 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=Comparison+of+two+pre-clinical+myocardial+infarct+models:+coronary+coil+deployment+versus+surgical+ligation.">Comparison of two pre-clinical myocardial infarct models: coronary coil deployment versus surgical ligation.</a> Journal of Translational Medicine. 12, 137 (2014).</li><li>Domkowski, P. W., Hughes, G. C., Lowe, 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=Ameroid+constrictor+versus+hydraulic+occluder:+creation+of+hibernating+myocardium.">Ameroid constrictor versus hydraulic occluder: creation of hibernating myocardium.</a> The Annals of Thoracic Surgery. 69 (6), 1984 (2000).</li><li>Tuzun, E., 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=Correlation+of+ischemic+area+and+coronary+flow+with+ameroid+size+in+a+porcine+model.">Correlation of ischemic area and coronary flow with ameroid size in a porcine model.</a> Journal of Surgical Research. 164 (1), 38-42 (2010).</li><li>Weism&#252;ller, P., Mayer, U., Richter, P., Heieck, F., Kochs, M., Hombach, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chemical+ablation+by+subendocardial+injection+of+ethanol+via+catheter+-+preliminary+results+in+the+pig+heart.">Chemical ablation by subendocardial injection of ethanol via catheter - preliminary results in the pig heart.</a> European Heart Journal. 12 (11), 1234-1239 (1991).</li><li>Haines, D., Verow, A., Sinusas, A., Whayne, J., DiMarco, 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+ethanol+ablation+in+swine:+characterization+of+myocardial+injury+in+target+and+remote+vascular+beds.">Intracoronary ethanol ablation in swine: characterization of myocardial injury in target and remote vascular beds.</a> Journal of Cardiovascular Electrophysiology. 5 (1), 41-49 (1994).</li><li>Li, K., Wagner, L., Moctezuma-Ramirez, A., Vela, D., Perin, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+robust+percutaneous+myocardial+infarction+model+in+pigs+and+its+effect+on+left+ventricular+function.">A robust percutaneous myocardial infarction model in pigs and its effect on left ventricular function.</a> Journal of Cardiovascular Translational Research. , (2021).</li><li>Eldar, M., Ohad, D., Bor, A., Varda-Bloom, N., Swanson, D., Battler, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+closed-chest+pig+model+of+sustained+ventricular+tachycardia.">A closed-chest pig model of sustained ventricular tachycardia.</a> Pacing and Clinical Electrophysiology : PACE. 17 (10), 1603-1609 (1994).</li><li>Dib, N., Diethrich, E. B., Campbell, A., Gahremanpour, A., McGarry, M., Opie, S. 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(86), e51269 (2014).</li><li>Kumar, 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=Animal+models+of+myocardial+infarction:+Mainstay+in+clinical+translation.">Animal models of myocardial infarction: Mainstay in clinical translation.</a> Regulatory Toxicology And Pharmacology RTP. 76, 221-230 (2016).</li></ol>

A coil deployed in a coronary artery provides a reproducible and consistent pre-clinical non-reperfused MI model in swine that can be used to develop and test new cardiovascular therapeutic strategies.
In our hands, mortality at follow-up was 19% related to complications of MI, mostly within the first 24 h of the procedure. All these deaths are related to the natural history of the non-reperfused MI and were the primary outcomes of the study. One of the most critical steps in this protocol rel...

Myocardial infarction (MI) is the most prevalent cause of mortality, morbidity, and disability worldwide1. Despite current therapeutic advances, a significant proportion of patients develop adverse ventricular remodeling and progressive heart failure following MI, resulting in poor prognosis due to ventricular dysfunction and sudden death2,3,4. New therapeutic options to repair and/or regenerate injured myocardium are thus under scrutiny, and translational MI animal models are crucial in testing their safety and efficacy. Although several models have been used for cardiovascular research, including rats5,6, mice7,8, dogs9, and sheep10, pigs are one of the best choices for modeling cardiac ischemia studies because of their high similarity to humans in terms of heart size, coronary artery anatomy, cardiac kinetics, physiology, metabolism, and the post-MI healing process11,12,13,14,15.
In this context, many different open-surgical and percutaneous approaches are available to develop MI swine models. The open-chest approach involves a left lateral thoracotomy procedure and is useful in performing surgical coronary artery ligation16,17, myocardial cryo-injury, cauterization12, and coronary artery placement of a hydraulic occlude18 or an ameroid constrictor19, among others. Surgical coronary occlusion has been extensively used to test new therapeutic options such as cardiac tissue engineering and cell therapy, as it allows wide access and visual assessment of the heart; however, in contrast to human MI, it can result in surgical adhesions, adjacent scarring, and postoperative inflammation17. Myocardial cryo-injury and cauterization are easily reproducible techniques but do not reproduce the pathophysiological MI progression observed in humans12. On the other hand, several percutaneous techniques have been developed to produce temporary or permanent coronary blocking. These comprise transcoronary or intracoronary ethanol ablation20,21, occlusion by balloon angioplasty22, or delivery of thrombogenic materials such as agarose gel beads23, fibrinogen mixtures9, or coil embolization17,24. While balloon angioplasty is better suited for ischemia/reperfusion studies, coronary coil deployment is one of the best choices for modeling non-revascularized MI. This percutaneous approach is feasible, consistently reproducible, and avoids open-chest surgery. It allows precise control of the infarct location and results in pathophysiology similar to that of a human non-reperfused MI. Moreover, coil embolization is suitable for modeling acute, sub-acute, or chronic MI; chronic congestive heart failure; or valvular disease17.
The present protocol aims to describe how to develop an MI swine model by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, a coil is deployed at the target branch artery under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>6-F JR4 0-71&#34;guiding catheter</td>
			<td>Medtronic</td>
			<td>LA6JR40</td>
			<td>6F JR4 90 cm Guiding catheter</td>
		</tr>
		<tr>
			<td>Adrenaline 1 mg/mL</td>
			<td>B.Braun</td>
			<td>National Code (NC). 602486</td>
			<td>Adrenaline</td>
		</tr>
		<tr>
			<td>Atropine 1 mg/mL</td>
			<td>B.Braun</td>
			<td>NC. 635649</td>
			<td>Atropine</td>
		</tr>
		<tr>
			<td>Betadine</td>
			<td>Mylan</td>
			<td>NC. 694109-1</td>
			<td>Povidone iodine solution</td>
		</tr>
		<tr>
			<td>Bupaq 0.3 mg/mL</td>
			<td>Richter Pharma AG</td>
			<td>NC. 578816.6</td>
			<td>Buprenorphine</td>
		</tr>
		<tr>
			<td>Dexdomitor 0.5 mg/mL</td>
			<td>Orion Pharma</td>
			<td>NC. 576303.3</td>
			<td>Dexmedetomidine</td>
		</tr>
		<tr>
			<td>Draxxin</td>
			<td>Zoetis</td>
			<td>NC. 576313.2</td>
			<td>Tulathromycin</td>
		</tr>
		<tr>
			<td>EMERALD Guidewire</td>
			<td>Cordis</td>
			<td>502-585</td>
			<td>0.035-inch J-tipped wire</td>
		</tr>
		<tr>
			<td>External defibrillator</td>
			<td>DigiCare</td>
			<td>CS81XVET</td>
			<td>Manual external defibrillator</td>
		</tr>
		<tr>
			<td>Fendivia 100 &#181;g/h</td>
			<td>Takeda</td>
			<td>NC. 658524.5</td>
			<td>Fentanyl transdermal patch</td>
		</tr>
		<tr>
			<td>Guidewire Introducer Needle 18 G x 7 cm</td>
			<td>Argon</td>
			<td>GWI1802</td>
			<td>Introducer needle</td>
		</tr>
		<tr>
			<td>Heparine 1%</td>
			<td>ROVI</td>
			<td>NC. 641647.1</td>
			<td>Heparin</td>
		</tr>
		<tr>
			<td>Hi-Torque VersaTurn F</td>
			<td>Abbott</td>
			<td>1013317J</td>
			<td>0.014-inch 200 cm Guidewire</td>
		</tr>
		<tr>
			<td>IsoFlo</td>
			<td>Zoetis</td>
			<td>50019100</td>
			<td>Isoflurane</td>
		</tr>
		<tr>
			<td>Ketamidor</td>
			<td>Richter Pharma AG,</td>
			<td>NC. 580393.7</td>
			<td>Ketamine</td>
		</tr>
		<tr>
			<td>Lidocaine 50 mg/mL</td>
			<td>B.Braun</td>
			<td>NC. 645572.2</td>
			<td>Lidocaine</td>
		</tr>
		<tr>
			<td>MD8000vet</td>
			<td>Meditech Equipment</td>
			<td>MD8000vet</td>
			<td>Multi-parameter monitor</td>
		</tr>
		<tr>
			<td>Midazolam</td>
			<td>Laboratorios Normon</td>
			<td>NC. 624437.1</td>
			<td>Midazolam</td>
		</tr>
		<tr>
			<td>Prelude.6F.11 cm (4.3&#34;).0.035&#34; (0.89 mm).50 cm (19.7&#34;).Double Ended.Stainless Steel.6F.16</td>
			<td>Merit</td>
			<td>PSI-6F-11-035</td>
			<td>6F Vascular sheath</td>
		</tr>
		<tr>
			<td>Propovet Multidosis 10 mg/mL</td>
			<td>Zoetis</td>
			<td>NC. 579742.7</td>
			<td>Propofol</td>
		</tr>
		<tr>
			<td>RENEGADE STC-18 150/20/STRAIGHT/1RO</td>
			<td>Boston Scientific</td>
			<td>M001181370</td>
			<td>150 cm length with 0.017-inch inner diameter Microcatheter</td>
		</tr>
		<tr>
			<td>Ruschelit</td>
			<td>Teleflex</td>
			<td>112482</td>
			<td>Endotracheal tube with balloon (#6.5)</td>
		</tr>
		<tr>
			<td>SPUR II</td>
			<td>Ambu</td>
			<td>325 012 000</td>
			<td>Airway mask bag unit-ventilation (AMBU)</td>
		</tr>
		<tr>
			<td>Vasofix 20 G</td>
			<td>B.Braun</td>
			<td>4269098</td>
			<td>20 G Cannula</td>
		</tr>
		<tr>
			<td>Visipaque 320 mg/mL USB 10 x 200 mL</td>
			<td>General Electrics</td>
			<td>1177612</td>
			<td>Iodinated contrast medium</td>
		</tr>
		<tr>
			<td>VortX-18 Diamond 3 mm/3.3 mm</td>
			<td>Boston Scientific</td>
			<td>M0013822030</td>
			<td>Coil</td>
		</tr>
		<tr>
			<td>WATO EX-35</td>
			<td>Mindray</td>
			<td>WATO EX-35Vet</td>
			<td>Anesthesia machine</td>
		</tr>
	</tbody>
</table>

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 and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

MI survival rates and location 
Fifty-seven pigs underwent coronary coil implantation in the LCX marginal branch (n = 25; 12 females and 13 males) or in the LAD between the first and the second diagonal branches (n = 32; 16 females and 16 males) of the coronary artery and were followed up for 30 days. The survival rate of animals submitted to an MI at the LCX marginal branch was 80% (n = 20). Three pigs died as a result of fatal complications related to atrioventricular (AV) block and asystole befor...

Watch this Scientific Journal Video about Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model at JoVE.com

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) animal models that emulate the natural process of the disease in humans are crucial to understanding pathophysiological mechanisms and testing the safety and efficacy of new emergent therapies. Here, we describe an MI swine model created by deploying a percutaneous embolization coil.

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

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A Cryoinjury Model to Study Myocardial Infarction in the Mouse

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

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 ...

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

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

Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model

One of the major issues facing current cardiac stem cell therapies for preventing postinfarct heart failure is the low retention and survival rates of ...