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 X Large White pigs (30-35 kg) of either sex.</li>
	<li>Keep the animals in a fasting state for 12 h prior to the procedure.</li>
</ol>
2. Sedation, anesthesia, and analgesia
<ol>
	<li>Sedate the animal with an intramuscular (IM) injection of ketamine (3 mg/kg), midazolam (0.3 mg/kg), and dexmedetomidine (0.03 mg/kg). Wait for approximately 10-15 min.</li>
	<li>Once the pig is sedated, ventilate it with an oxygen (90-100%)-isoflurane (1-2%) mixture and a face mask to ensure optimal sedation.</li>
	<li>Place vet ointment on the pig&#39;s eyes to prevent dryness. 
	NOTE: Repeat every 20 min.</li>
	<li>Place intravenously (IV) a 20 G catheter in a lateral ear vein. Administer propofol (1-2 mg/kg) to induce anesthesia.</li>
	<li>Once the pig has no swallowing reflex, intubate the animal using an endotracheal tube (size 6.5-7.0 for 30-35 kg). 
	NOTE: Adjust the size of the endotracheal tube according to the size of the pig. Intubation should be carried out rapidly to prevent a deeper anesthetic plane and prolonged apnea.</li>
	<li>Administer IV buprenorphine (0.01 mg/kg) for intra-surgical analgesia. Use a fentanyl transdermal patch (100 &#181;g/h) for post-operative analgesia. 
	NOTE: The fentanyl patch is applied to the inguinal skin, and it is active for 72 h to limit postoperative pain. Its pharmacological effect does not start immediately after delivery, thus apply it before starting the procedure.</li>
	<li>Perform airway mask bag unit-ventilation (20 inflations/min) during the transport of the pig to the vascular interventional radiology (VIR) room.</li>
	<li>Connect the endotracheal tube to the anesthesia machine equipped with an airway sensor and capnography recording.</li>
	<li>Start mechanical positive pressure ventilation with FiO2 0.50, using a tidal volume of 10 mL/kg and a frequency of 16-20 breaths/min. Maintain the anesthesia with isoflurane (1-3%). 
	&#8203;NOTE: To confirm the correct surgical anesthetic plane, the animal should not be respiring spontaneously nor have corneal or pupillary light reflexes.</li>
</ol>
3. Hemodynamic monitoring and preparation of the surgical area
<ol>
	<li>Place the animal on the operating table in the supine position and fix the limbs to the table with tape or bandage.</li>
	<li>Place electrocardiogram (ECG) probes subcutaneously in the animal&#39;s extremities for recording changes in ST-segment, T-waves, and heart rate during the experimental procedure.</li>
	<li>Place a pulse oximeter on the tongue or a corner of the lip of the animal and the non-invasive pressure cuff on the forelimb.</li>
	<li>Measure the rectal/esophageal temperature with a probe.</li>
	<li>Clean the right femoral area with surgical soap followed by alternating antiseptic povidone-iodine solution and alcohol 3 times under sterile conditions.</li>
	<li>Ensure that the surgeon performs surgical handwashing and wears a sterile gown and sterile gloves.</li>
	<li>Cover the animal with a sterile surgical drape.</li>
	<li>Prepare and flush with heparinized saline solution the needle, a 6F vascular sheath, a 0.035-inch J-tipped wire, a 6F JR4 90-cm guiding catheter, a 0.014-inch 200-cm guidewire, a 150-cm length/0.017-inch inner diameter microcatheter, and the contrast medium injection manifold kit.</li>
</ol>
4. Vascular access
<ol>
	<li>Puncture the right femoral artery via a percutaneous approach with ultrasound-guided puncture. Locate the bifurcation between the superficial femoral artery and the deep femoral artery.</li>
	<li>Position the transducer 2-3 cm proximal to the bifurcation, in the common femoral artery, and align the center of the transducer with the common femoral artery.</li>
	<li>Position the needle in the center of the transducer and puncture the artery at an angulation of approximately 45&#176;. Subsequently, insert a 6F vascular sheath using the modified Seldinger technique26. 
	NOTE: In case of significant spasm or hematoma, crossover to the contralateral femoral artery.</li>
	<li>Flush the catheters with heparinized saline solution. (5000 IU unfractionated heparin/1000 mL of 0.9% NaCL).</li>
	<li>Administer heparin through the sheath (300 IU/kg).</li>
</ol>
5. Coronary angiography
<ol>
	<li>Insert the J-tip wire into the JR4 guide catheter and advance the wire through the sheath into the ascending aorta, and then place the catheter up over the valvular surface.</li>
	<li>Remove the wire and connect the catheter to the injection manifold system. Purge the entire system.</li>
	<li>Under fluoroscopy, engage the catheter into the left main coronary artery and inject 10 mL of iodinated contrast medium to visualize the left coronary system (Figure 1A, C). 
	NOTE: It is important to ensure that the arterial pressure waveform is not damped before injecting to avoid the risk of coronary dissection.</li>
	<li>Perform angiograms in two orthogonal views: left anterior oblique 40&#176; and right anterior oblique 30&#176; projections.</li>
	<li>Advance a 0.014-inch guidewire pre-assembled on the microcatheter to the middle left anterior descending (LAD) or distal left circumflex (LCX) coronary artery under fluoroscopic guidance.</li>
</ol>
6. Coil implantation
<ol>
	<li>Under fluoroscopic guidance, advance the microcatheter through the wire to the desired location where the coil implant should be deployed. In the case of LAD occlusion, place the coil distal to the first diagonal branch, and for LCX, place the coil distal to the first marginal branch. 
	NOTE: Proximal approaches (before the first diagonal or first marginal branches) have very low survival rates.</li>
	<li>Remove the wire and select the coil. 
	NOTE: It is important to select the optimal coil size and length. A small or short coil may not position well in the vessel lumen and has a very high risk of distal migration due to contrast injections or spontaneous, resulting in smaller infarct size. A large or long coil may prolapse proximal to the vessel and produce a larger infarct than desired. The choice of the correct coil is especially important if non-detectable coils are used, as they cannot be removed. The optimal size is 1-2 mm larger than the lumen of the vessel to be embolized, and the length between 20-60 mm is usually adequate for 30-40-kg pigs.</li>
	<li>Deliver the coil via microcatheter and slowly inject 5 mL of iodinated contrast medium under fluoroscopy to visualize the correct position of the coil.</li>
	<li>Remove the microcatheter inside the guide catheter and place the guide in a side branch to perform control injections and to ensure access to the artery in case a second coil needs to be implanted.</li>
	<li>Wait for the coil to thrombose and occlude the artery. 
	&#8203;NOTE: When the artery is occluded, changes in the electrocardiogram can be observed. Another way to check complete arterial occlusion is to perform slow injections of iodinated contrast every 10 min (Figure 1B, D). If the artery does not occlude within 20-30 min, another coil implant may be required.</li>
</ol>
7. End of procedure
<ol>
	<li>Once the artery is occluded, administer a continuous IV infusion of lidocaine (50-100 &#181;g/kg/min) for at least 1 h to prevent arrhythmic episodes.</li>
	<li>Perform an angiogram to ensure that there is no flow distal to the occlusion.</li>
	<li>Remove the wire, microcatheter, and guiding catheter.</li>
	<li>Remove the sheath and perform manual compression for 20 min.</li>
</ol>
8. Postoperative procedure and animal recovery
<ol>
	<li>Monitor the animal until it is fully recovered, using ECG, rectal temperature, pulse oximetry, and capnography. 
	NOTE: In case of ventricular arrhythmias, administer a bolus of lidocaine (1.5-3.5 mg/kg).</li>
	<li>Administer an IM injection of tulathromycin (2.5 mg/kg) as prophylactic postoperative antibiotic therapy. For post-surgical analgesia, a transdermal fentanyl patch is administered before the surgical procedure (step 2.6).</li>
	<li>Turn off the isoflurane and maintain mechanical ventilation until the animal begins to breathe spontaneously.</li>
	<li>When the pig recovers the swallowing reflex, remove the endotracheal tube. NOTE: Check if the animal has a good SpO2 (more than 95%) before and after extubation.</li>
	<li>Transport the animal to an individual cage. Position the animal over a hot water blanket and cover it with a thermal drape to avoid post-surgical hypothermia. 
	NOTE: Do not return the pig to the company of other animals until it has fully recovered.</li>
	<li>Monitor the animal until it has regained sufficient consciousness to maintain sternal recumbency.</li>
</ol>
9.&#160;Postoperative pain assessment and monitoring 
<ol>
	<li>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>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>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>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>

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The authors have nothing to disclose

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 relies on the entry of the microcatheter into the coronary arteries. In some cases, microcatheter advancement caused a vagal reaction leading to severe hypotension, AV block, and finally asystole. Nevertheless, this can be avoided by administering an IV bolus of adrenaline (0.001 mg/kg) before advancing the microcatheter. Another complication is the occurrence of malignant arrhythmias that can lead to VF. These episodes usually occur 30 min after MI instauration. We recommend&#160;using a lidocaine continuous infusion rate (50-100 &#181;g/kg/min) for at least 1h to reduce the risk of ventricular arrhythmias. As an alternative, a continuous infusion of amiodarone (50-80 &#181;g/kg/min) can be administered. However, if ventricular arrhythmic events occur, we recommend delivering a bolus of lidocaine (1.5&#8211;3.5 mg/kg). In case of severe bradycardia, we recommend the administration of atropine bolus (0.01 mg/kg), noradrenaline perfusion (0.05-3 &#181;g/kg/min) for mild or moderate hypotension, and adrenaline (0.03 mg/kg) for severe hypotension, electromechanical dissociation, AV block, or asystole. However, when a VF occurs, a 320J ventricular defibrillation has to be applied with a monophasic cardiac defibrillator and repeated until the animal recovers its cardiac rhythm. When several ventricular defibrillations are needed or asystole occurs, perform manual chest compressions (80-90 compressions/min), depressing the ribcage 4 inches, and connect the animal to the mechanical ventilator under 100% O2.
If the interventional procedure is extended for more than one hour, it is useful to monitor the anticoagulation level with the activated clotting time test to ensure that it is greater than 300 seconds. If it is shorter, an extra dose of heparin should be administered.&#160;
In case an occlusive thrombus does not form after coronary artery coil deployment, we recommend the placement of another coil. Another option could be to administrate protamine (1mg/100IU of UFH) to facilitate clot formation, although there is a risk of thrombus formation in the guiding catheter and subsequent embolization during control injection.
Many other occlusion models have been described to simulate MI based on cessation of coronary flow by arterial ligation, an ameroid constrictor, or balloon inflation. However, a deployed coil sets off the coagulation cascade with thrombus formation that occludes the coronary artery. This mechanism simulates as closely as possible the pathophysiology of human MI, compared with other non-invasive techniques like balloon occlusion. Despite the fact that non-reperfused MI results in more extensive scarring, less viable myocardium, and a greater reduction in terms of cardiac function than ischemia-reperfusion models27,&#160;it is more suitable for screening anti-inflammatory therapies, reverse cardiac remodeling, and gene or stem cell therapy for the treatment of cardiovascular disease28.

An erratum was issued for:&#160;<a href="https://www-jove-com.remotexs.ntu.edu.sg/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.remotexs.ntu.edu.sg/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><tbody><tr><td>6-F JR4 0-71&quot;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 &amp;micro;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&quot;).0.035&quot; (0.89 mm).50 cm (19.7&quot;).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 before coil deployment, and 2 pigs died after ventricular fibrillation (VF) related to transmural MI after coil placement. The survival rate of animals submitted to MI at LAD was 72% (n = 23): 1 pig died due to an AV block and asystole after coil deployment and 8 animals after VF (5 after coil deployment, 2 at 12-48 h post-MI, and one 26 days post-MI). The survival rates differed between the LCX marginal branch (2-2.5 mm in diameter) and middle LAD (2.5-3 mm in diameter) MI, probably due to the larger infarct extension in the LAD model.
Magnetic resonance imaging (MRI) analysis was performed in all animals 30 days post-MI. Figure 2 illustrates late gadolinium-enhanced MRI images of the LCX marginal branch (Figure 2A,C) and distal LAD (Figure 2B,D) infarct models. As depicted, coil deployment in the LCX marginal coronary artery affects the LV lateral wall, while the interventricular septum is the most affected area in distal LAD placement. These results were also confirmed after heart sectioning (Figure 2E,F).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/63172/63172fig01.jpg" /> 
Figure 1: Coronary angiography, anteroposterior projection. Representative images of pre- (A,B) and post-coil (white arrows) deployment (C,D) in the LCX marginal branch and distal LAD coronary artery. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/63172/63172fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/63172/63172fig02.jpg" /> 
Figure 2: Magnetic resonance imaging and cardiac tissue sections. Representative T1 3-chamber (A,B) and short-axis (C,D) delayed enhancement images for LCX marginal and distal LAD infarction. Images reveal healthy (black) and infarcted (white) myocardium. Photographs of heart sections after LCX marginal (E) and distal LAD MI (F). Arrows indicate the location and extension of the infarcted area. Scale bar = 1 cm <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/63172/63172fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

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 ...

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

Nanyang Technological University

Research

JoVE Journal

Medicine

2.9K Views.  Germans Trias i Pujol Health Research Institute (IGTP). Dit protocol is belangrijk omdat het het mogelijk maakt om een hartinfarct uit te voeren in een translationeel diermodel, op een haalbare en reproduceerbare manier vergelijkbaar met de mens. Het belangrijkste voordeel van deze procedure is dat het de traditionele open borstoperatie en de daaropvolgende postoperatieve ontsteking vermijdt. En daarom is een van de beste keuzes die een menselijk myocardinfarct nabootst.Deze techniek is geschikt voor het modelleren van myocardinfarct en hog...

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

Gene Transfer for Ischemic Heart Failure in a Preclinical Model

Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine their efficacy and safety.
Gene therapy using viral vectors is one of the most promising approaches for treating cardiac diseases. Viral delivery of various different genes by changing the carrier gene has immeasurable therapeutic potential.
In this video, the full process of an animal model of heart failure creation followed by gene transfer is presented using a swine model. First, myocardial infarction is created by occluding the proximal left anterior descending coronary artery. Heart remodeling results in chronic heart failure. Unique to our model is a fairly large scar which truly reflects patients with severe heart failure who require aggressive therapy for positive outcomes. After myocardial infarct creation and development of scar tissue, an intracoronary injection of virus is demonstrated with simultaneous nitroglycerine infusion. Our injection method provides simple and efficient gene transfer with enhanced gene expression. This combination of a myocardial infarct swine model with intracoronary virus delivery has proven to be a consistent and reproducible methodology, which helps not only to test the effect of individual gene, but also compare the efficacy of many genes as therapeutic candidates.

A method of gene transfer for the treatment of ischemic heart failure is described using a swine model of myocardial infarction. Our simple and reproducible method enables us to readily evaluate the efficacy of various gene transfers with a very simple and reproducible way.

Various emerging technologies are being developed for patients with heart failure. Well-established preclinical evaluations are necessary to determine ...

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 ...

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 ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

Cardiovascular disease remains the number one cause of mortality in the United States. There are numerous approaches to treating these diseases, but regardless of the approach, an in vivo model is needed to test each treatment. The pig is one of the most used large animal models for cardiovascular disease. Its heart is very similar in anatomy and function to that of a human. The ameroid placement technique creates an ischemic area of the heart, which has many useful applications in studying myocardial infarction. This model has been used for surgical research, pharmaceutical studies, imaging techniques, and cell therapies.
There are several ways of inducing an ischemic area in the heart. Each has its advantages and disadvantages, but the placement of an ameroid constrictor remains the most widely used technique. The main advantages to using the ameroid are its prevalence in existing research, its availability in various sizes to accommodate the anatomy and size of the vessel to be constricted, the surgery is a relatively simple procedure, and the post-operative monitoring is minimal, since there are no external devices to maintain. This paper provides a detailed overview of the proper technique for the placement of the ameroid constrictor.

The purpose of this protocol is to demonstrate the placement of a delayed constricting device (an ameroid constrictor) around a coronary artery in a swine model. This device creates an ischemic area of the heart that is useful for studying new diagnostic imaging techniques and new methods of treatment.

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

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 ...

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 ...

Standardized Model of Ventricular Fibrillation and Advanced Cardiac Life Support in Swine

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as preclinical settings. Prospective randomized trials in human subjects are difficult to design and ethically ambiguous, which results in a lack of evidence-based therapies. The model presented in this report represents one of the most common causes of cardiac arrests, ventricular fibrillation, in a standardized setting in a large animal model. This allows for reproducible observations and various therapeutic interventions under clinically accurate conditions, hence facilitating the generation of better evidence and eventually the potential for improved medical treatment.

Cardiopulmonary resuscitation and defibrillation are the only effective therapeutic options during cardiac arrest caused by ventricular fibrillation. This model presents a standardized regimen to induce, assess, and treat this physiological state in a porcine model, thus providing a clinical approach with various opportunities for data collection and analysis.

Cardiopulmonary resuscitation after cardiac arrest, independent of its origin, is a regularly encountered medical emergency in hospitals as well as ...

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 ...

Swine Models of Aneurysmal Diseases for Training and Research

Large animal models, specifically swine, are widely used to research cardiovascular diseases and therapies, as well as for training purposes. This paper describes two different aneurysmal swine models that may help researchers to study new therapies for aneurysmal diseases. These aneurysmal models are created by surgically adding a pouch of tissue to carotid arteries in swine. When the model is used for research, the pouch must be autologous; for training purposes, a synthetic pouch suffices.
First, the right external jugular vein (EJV) and right common carotid artery (CCA) must be surgically exposed. The EJV is ligated and a vein pouch fashioned from a short segment. This pouch is then sutured to an elliptical arteriotomy performed in the CCA. Animals must be kept heparinized during model creation, and local vasodilators may be used to decrease vasospasms. Once the suture is completed, correct blood flow should be inspected, checking for bleeding from the suture line and vessel patency. Finally, the surgical incision is closed by layers and an angiography performed to image the aneurysmal model.
A simplification of this aneurysmal carotid model that decreases invasiveness and surgical time is the use of a synthetic, rather than venous, pouch. For this purpose, a pouch is tailored in advance with a segment of a polytetrafluoroethylene (PTFE) prosthesis, one end of which is sutured close using polypropylene vascular suture and sterilized prior to surgery. This "sac" is then attached to an arteriotomy performed in the CCA as described. 
Although these models do not reproduce many of the physiopathological events related to aneurysm formation, they are hemodynamically similar to the situation found in the clinical setting. Therefore, they can be used for research or training purposes, allowing physicians to learn and practice different endovascular techniques in animal models that are close to the human system.

Description of two different aneurysmal swine models for neuroradiology training courses and research studies. This study provides evidence of the feasibility of these aneurysm porcine model creations and the reproducible methods that are close to the clinical setting.

Large animal models, specifically swine, are widely used to research cardiovascular diseases and therapies, as well as for training purposes. This paper ...

Delivery of Cardioactive Therapeutics in a Porcine Myocardial Infarction Model

Myocardial infarction is one of the leading causes of death and disability worldwide, and there is an urgent need for novel cardioprotective or regenerative strategies. An essential component of drug development is determining how a novel therapeutic is to be administered. Physiologically relevant large animal models are of critical importance in assessing the feasibility and efficacy of various therapeutic delivery strategies. Due to their similarities to humans in cardiovascular physiology, coronary vascular anatomy, and heart weight to body weight ratio, swine is one of the preferred species in the preclinical evaluation of new therapies for myocardial infarction. The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. After percutaneously induced myocardial infarction, female landrace swine received treatment with novel agents through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump. The procedures employed for each technique are reproducible, resulting in reliable cardioactive drug delivery. These models can be easily adapted to suit individual study designs, and each of these delivery techniques can be used to investigate a variety of possible interventions. Therefore, these methods are a useful tool for translational scientists pursuing novel biological approaches in cardiac repair following myocardial infarction.

The present protocol describes three methods of administering cardioactive therapeutic agents in a porcine model. Female landrace swine received treatment through either: (1) thoracotomy and transepicardial injection, (2) catheter-based transendocardial injection, or (3) intravenous infusion via jugular vein osmotic minipump.

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

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