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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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...

An erratum was issued for:&#160;<a href="https://www.jove.com/t/63172">Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model</a>. The Protocol and Discussion sections were updated.
Step 3.5 was updated from:
Clean the right femoral area with surgical soap and antiseptic povidone-iodine solution under sterile conditions
to:
Clean the right femoral area with surgical soap followed by alternating antiseptic povidone-iodine solution and alcohol 3 times under sterile conditions.
Section 9 was updated from:
9. Euthanasia method
<ol>
	<li>Under previous sedation and anesthesia, as previously described, administer an IV sodium thiopental overdose (200 mg/kg).</li>
	<li>Confirm cardiorespiratory arrest and death by monitoring vital signs (electrocardiogram, blood pressure, capnography).</li>
</ol>
to:
9. Postoperative pain assessment and monitoring
<ol>
	<li class="jove_content">During the post-surgical follow-up, monitor the general condition of the animals, including the respiratory rate, food and water intake, activity and interaction with the other individuals, appearance and coloration of the skin, and the evolution of the surgical wound.</li>
	<li class="jove_content">Apply a daily supervision protocol according to the following scoring criteria: 
	- Weight: 
	0: Normal 
	1: &#60;10% weight loss 
	2: 10-20% weight loss 
	3:&#62; 20% weight loss 
	 
	- Body condition: 
	0: Good: non-prominent vertebrae, pelvic or spinal bones 
	2: Regular: evidence of spinal segmentation, palpable pelvic bones 
	3: Emaciation: extremely marked skeleton, little or no meat to cover 
	 
	- Behavior: 
	0: Normal: Active and interactive in your environment 
	1: Slight decline in activity and less interactive 
	2: Abnormal: pronounced decline in activity, isolated 
	3: Abnormal: Immobile or hyperactivity, possible self-harm 
	 
	- Physical appearance: 
	0: Normal: skin/hair shiny and eyes bright 
	1: Disappears embalming, skin/hair without shine 
	2: Poor skin/nasal secretions 
	3: Poor skin, abnormal or hunched posture 
	 
	- Behavioral disorders: 
	0: None 
	1: Inability to move normally 
	2: Unable to reach food/drink, isolated from other animals 
	3: Intention to hide/corner, does not respond to stimuli (dying) 
	 
	- Clinical signs: 
	0: None 
	1: Hypothermia, fever, mild respiratory failure 
	2: Infection of the surgical wound, moderate respiratory failure with muco-bloody secretions 
	3: Heart failure, severe respiratory failure (cyanosis, open mouth) 
	 
	Score: 
	- 1-5: Supervise the animals once a day. 
	- 6-12: Provide supportive therapy if necessary. 
	- Any animal with a score of 3 in any of the above parameters or with a total score &#62;12 will be euthanized. 
	NOTE: The animals should be monitored daily by the animal care staff and twice a week by the research and veterinary team.</li>
	<li class="jove_content">Although no pain and distress are expected from the procedure, if any animal shows signs of pain, give analgesic therapy (tramadol, oral, 2-4 mg/kg, daily). If any animal does not respond to analgesic medication and shows signs of chronic pain (very low probability), euthanize the animal with an anesthetic overdose (sodium thiopental, IV, 200 mg/kg).</li>
	<li class="jove_content">If the surgical wound shows signs of infection (low probability) despite the antibiotic therapy administered, treat the wound daily and initiate a new antibiotic regimen (cefquinome sulphate, IM, 2 mg/kg, daily).</li>
</ol>
10. Euthanasia method
<ol>
	<li>Under previous sedation and anesthesia, as previously described, administer an IV sodium thiopental overdose (200 mg/kg).</li>
	<li>Confirm cardiorespiratory arrest and death by monitoring vital signs (electrocardiogram, blood pressure, capnography).</li>
</ol>

An erratum was issued for:&#160;<a href="https://www.jove.com/t/63172">Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model</a>. The Protocol and Discussion sections were updated.

Erratum: Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

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 ...

This protocol is important because it allows performing myocardial infarction in a translational animal model, in a feasible and reproducible way similar to human. The main advantage of this procedure is that it avoids the traditional open-chest surgery and the subsequent postoperative inflammation. And therefore is one of the best choices mimicking human myocardial infarction.This technique is suitable for modeling myocardial infarction and higher failure depending on the dissection of the ischemic area. Begin by placing the anesthetized animal on the operating table in the supine position and fix the limbs to the table with tape or bandage. Place the electrocardiogram probes subcutaneously in the animals'extremities for recording changes in the ST-segment, T-waves and heart rate during the experimental procedure.Place the pulse oximeter on the tongue or a corner of the animal's lip and the non-invasive pressure cuff on the for limb. Measure the temperature with a esophageal probe. Clean the right femoral area with surgical soap followed by alternating antiseptic povidone-iodine solution and alcohol three times under sterile conditions.Wash the hands surgically and wear sterile gown and sterile gloves. Then cover the animal with a sterile surgical drape. Flush the needle vascular sheath J-tipped wire, guiding catheter, guidewire microcatheter, and the contrast medium injection manifold kit with heparinized saline solution.Locate the bifurcation between the superficial and deep femoral arteries using ultrasound. Position the transducer two to three centimeters proximal to the bifurcation in the common femoral artery and align the center of the transducer with the common femoral artery. Now position the needle in the center of the transducer and puncture the artery at angulation of approximately 45 degrees.Subsequently, insert a six French vascular sheath using the modified Seldinger technique and administer heparin through the sheath. Begin by inserting the J-tip wire into the JR4r guide catheter and advance the wire through the sheath into the ascending aorta. Place the catheter up over the valvular surface.After removing the wire connect the catheter to the injection manifold system and purge the entire system. Under fluoroscopy, engage the catheter into the left main coronary artery and inject 10 milliliters of iodinated contrast medium to visualize the left coronary system. Perform angiograms in the left anterior oblique 40 degrees and right anterior oblique 30 degrees projections.Under fluoroscopic guidance, advance 0.014-inch guidewire pre-assembled on the microcatheter to the middle left anterior descending or distal left circumflex coronary artery. Under fluoroscopic guidance, advance the microcatheter through the wire to the desired location where the coil implant should be deployed. Remove the wire and select the coil.Deliver the coil via microcatheter and slowly inject five milliliters of iodinated contrast medium under fluoroscopy to visualize the correct position of the coil. Place the wire in a side branch to perform control injections and to ensure access to the artery if a second coil needs to be implanted. Wait for the coil to thrombose and occlude the artery.57 pigs underwent coronary coil implantation and their angiographic showed myocardial infarction in the distal left circumflex marginal branch or distal left anterior descending coronary artery. The mortality of this model was 19%related to complications of MI.Magnetic resonance imaging analysis of the left circumflex marginal branch and distal left anterior descending coronary infarctions was performed in all animals 30 days post myocardial infarction. The coil deployment in the left circumflex marginal coronary artery affected the left ventricular lateral wall.While the intra-ventricular septum is the most affected area in distal left anterior descending coronary placement. The infarcted areas post coil development in the left circumflex marginal coronary artery and the distal left anterior descending coronary were also confirmed after heart sectioning. The most important steps include, first, to place the microcatheter in the right position.Second, to choose the correct coil size and third to deliver it properly. Thanks to this model, researchers can explore new therapies and study the pathophysiological mechanism of myocardial infarction.

myocardial-infarction-percutaneous-embolization-coil-deployment-swine

Research

JoVE Journal

Medicine

Acute Myocardial Infarction in Rats

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial infarction (AMI). This model is also referred to as an acute ischemic cardiomyopathy or ischemia followed by reperfusion (IR); which is induced by an acute 30-minute period of ischemia by ligation of the left anterior descending artery (LAD) followed by reperfusion of the tissue by releasing the LAD ligation (Vasilyev and McConnell). This protocol will focus on assessment of the infarct size and the area-at-risk (AAR) by Evan's blue dye and triphenyl tetrazolium chloride (TTC) following 4-hours of reperfusion; additional comments toward the evaluation of cardiac function and remodeling by modifying the duration of reperfusion, is also presented. Overall, this AMI rat animal model is useful for studying the consequence of a myocardial infarction on cardiac pathophysiological and physiological function.

The rat model of acute myocardial infarction (AMI) is useful to study the consequence of a MI on cardiac pathophysiological and physiological function.

With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.

This protocol describes the porcine myocardial infarction (MI) model using a 90 min closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. Furthermore, the protocol for several outcome parameters, such as cardiac function, hemodynamics, microvascular resistance, and infarct size, are also presented.

Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One ...

A Hydrogel Construct and Fibrin-based Glue Approach to Deliver Therapeutics in a Murine Myocardial Infarction Model.

The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of treatments in vivo1. The traditional, established protocol has been further fine-tuned to minimize the damage to the animal. Notably, the pectoral muscle layers are teased away rather than simply cut, and the thoracotomy is approached intercostally as opposed to breaking the ribs in a sternotomy, preserving the integrity of the ribcage. With these changes, the overall stress on the animal is decreased. 
Stem cell therapies aimed to alleviate the damage caused by MIs have shown promise over the years for their pro-angiogenic and anti-apoptotic benefits. Current approaches of delivering cells to the heart surface typically involve the injection of the cells either near the damaged site, within a coronary artery, or into the peripheral blood stream2-4. While the cells have proven to home to the damaged myocardium, functionality is limited by their poor engraftment at the site of injury, resulting in diffusion into the blood stream5. This manuscript highlights a procedure that overcomes this obstacle with the use of a cell-encapsulated hydrogel patch. The patch is fabricated prior to the surgical procedure and is placed on the injured myocardium immediately following the occlusion of the left coronary artery. To adhere the patch in place, biocompatible external fibrin glue is placed directly on top of the patch, allowing for it to dry to both the patch and the heart surface. This approach provides a novel adhesion method for the application of a delicate cell-encapsulating therapeutic construct.

This protocol aims to alleviate the limitation of poor cell engraftment for stem cell treatment of myocardial infarctions through the use of a hydrogel system and a fibrin-based glue. With this approach, cell-to-tissue contact post-infarction can be maintained, increasing the therapeutic potential of beneficial agents at the site of injury.

The murine MI model is widely recognized in the field of cardiovascular disease, and has consistently been used as a first step to test the efficacy of ...

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are therefore required to confine cardiac damage, promote survival and reduce the disease burden of heart failure. Large animal experiments are an essential part in the translational process from experimental to clinical therapies. To optimize clinical translation, robust and representative outcome measures are mandatory. The present manuscript aims to address this need by describing the assessment of three clinically relevant outcome modalities in a pig acute myocardial infarction (AMI) model: infarct size in relation to area at risk (IS/AAR) staining, 3-dimensional transesophageal echocardiography (TEE) and admittance-based pressure-volume (PV) loops. Infarct size is the main determinant driving the transition from AMI to heart failure and can be quantified by IS/AAR staining. Echocardiography is a reliable and robust tool in the assessment of global and regional cardiac function in clinical cardiology. Here, a method for three-dimensional transesophageal echocardiography (3D-TEE) in pigs is provided. Extensive insight into cardiac performance can be obtained by admittance-based pressure-volume (PV) loops, including intrinsic parameters of myocardial function that are pre- and afterload independent. Combined with a clinically feasible experimental study protocol, these outcome measures provide researchers with essential information to determine whether novel therapeutic strategies could yield promising targets for future testing in clinical studies.

Reliable and accurate outcome assessment is the key for translation of preclinical therapies into clinical treatment. The current paper describes how to assess three clinically relevant primary outcome parameters of cardiac performance and damage in a pig acute myocardial infarction model.

Mortality after acute myocardial infarction remains substantial and is associated with significant morbidity, like heart failure. Novel therapeutics are ...

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction.

This protocol describes a highly reproducible model of cardiac regeneration by surgical induction of myocardial infarction in the left ventricle of postnatal day 1 mice. The method involves induction of hypothermic anesthesia and ligation of the left anterior descending coronary artery.

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved drug to prevent or reduce myocardial I/R injury. The study and understanding of the pathophysiological mechanisms of myocardial I/R injury is essential to develop successful treatments. Large animal experiments are an important step in translational methods. The porcine model of acute myocardial infarction has been established and described by ourselves and others. We aimed to further improve the value of the model by focusing in detail on the sampling techniques for use in future experiments. Furthermore, we emphasize small but important steps that can affect the quality of the final results. To mimic the clinical situation of myocardial I/R injury, a percutaneous coronary intervention (PCI) catheter was inserted into the left anterior descending coronary artery (LAD) of an anesthetized pig. &#176;&#176;&#176;This model mimics acute myocardial infarction and PCI treatment in humans with the possibility of accurately determining the area at risk as well as the necrotic- and viable ischemic tissue. Here the model was used to investigate the effect of a bicyclic peptide inhibitor of FXIIa. The model can also be modified to allow longer reperfusion times to study later effects of myocardial infarction.

Here we demonstrate a protocol to standardize sampling procedures of an established porcine model of acute myocardial infarction in order to increase its translational value in the understanding of the pathophysiology of myocardial ischemia/reperfusion injury and to test novel drug candidates.

Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved ...

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 demonstrate a murine cryoinjury infarct model that generates precise infarct sizes with high reproducibility and replicability. In brief, after intubation and sternotomy of the animal, the heart is lifted from the thorax. The probe of a handheld liquid nitrogen delivery system is applied onto the myocardial wall to induce cryoinjury. Impaired ventricular function and electrical conduction can be monitored with echocardiography or optical mapping. Transmural myocardial remodeling of the infarcted area is characterized by collagen deposition and loss of cardiomyocytes. Compared to other models (e.g., LAD-ligation), this model utilizes a handheld liquid nitrogen delivery system to generate more uniform infarct sizes.

This article demonstrates a model to study cardiac remodeling after myocardial cryoinjury in mice.

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 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.

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 (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

We describe a novel, cost-effective, and efficient technique for percutaneous delivery of three-dimensionally printed coronary implants to create closed-chest swine models of ischemic heart disease. The implants were fixed in place using a mother-and-child extension catheter with high success rate.

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 transplanted cells within the injured myocardium, limiting their therapeutic efficacy. Recently, the use of scaffolding biomaterials has gained attention for improving and maximizing stem cell therapy. The objective of this protocol is to introduce a simple and straightforward technique to transplant bone marrow-derived mesenchymal stem cells (MSCs) using injectable hydroxyphenyl propionic acid (GH) hydrogels; the hydrogels are favorable as a cell delivery platform for cardiac tissue engineering applications due to their ability to be cross-linked in situ and high biocompatibility. We present a simple method to fabricate MSC-loading GH hydrogels (MSC/hydrogels) and evaluate their survival and proliferation in three-dimensional (3D) in vitro culture. In addition, we demonstrate a technique for intramyocardial transplantation of MSC/hydrogels in mice, describing a surgical procedure to induce myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation and subsequent MSC/hydrogels transplantation.

Stem cell-based therapy has emerged as an efficient strategy to repair injured cardiac tissues after myocardial infarction. We provide an optimal in vivo application for stem cell transplantation using gelatin hydrogels that are able to be enzymatically cross-linked.

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