Method Article

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

DOI:

10.3791/63172

November 4th, 2021

In This Article

Erratum Notice

Important: There has been an erratum issued for this article. Read More ...

Erratum

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Formal Correction: Erratum: Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model
Posted by JoVE Editors on 5/26/2022. Citeable Link.

An erratum was issued for: Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model. 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

  1. Under previous sedation and anesthesia, as previously described, administer an IV sodium thiopental overdose (200 mg/kg).
  2. Confirm cardiorespiratory arrest and death by monitoring vital signs (electrocardiogram, blood pressure, capnography).

to:

9. Postoperative pain assessment and monitoring

  1. 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.
  2. Apply a daily supervision protocol according to the following scoring criteria:
    - Weight:
    0: Normal
    1: <10% weight loss
    2: 10-20% weight loss
    3:> 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 >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.
  3. 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).
  4. 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).

10. Euthanasia method

  1. Under previous sedation and anesthesia, as previously described, administer an IV sodium thiopental overdose (200 mg/kg).
  2. Confirm cardiorespiratory arrest and death by monitoring vital signs (electrocardiogram, blood pressure, capnography).

Summary

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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.

Abstract

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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.

Introduction

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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 b....

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Protocol

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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. Preprocedural preparation of animals

  1. Use crossbred Landrace X Large White pigs (30-35 kg) of either sex.
  2. Keep the animals in a fasting state for 12 h prior to the procedure.

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Results

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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 .......

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Discussion

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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.......

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Disclosures

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The authors have nothing to disclose

Acknowledgements

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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 Española de Cardiología, 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-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). Dr. Fadeuilhe was sup....

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
6-F JR4 0-71"guiding catheterMedtronicLA6JR406F JR4 90 cm Guiding catheter
Adrenaline 1 mg/mLB.BraunNational Code (NC). 602486Adrenaline
Atropine 1 mg/mLB.BraunNC. 635649Atropine
BetadineMylanNC. 694109-1Povidone iodine solution
Bupaq 0.3 mg/mLRichter Pharma AGNC. 578816.6Buprenorphine
Dexdomitor 0.5 mg/mLOrion PharmaNC. 576303.3Dexmedetomidine
DraxxinZoetisNC. 576313.2Tulathromycin
EMERALD GuidewireCordis502-5850.035-inch J-tipped wire
External defibrillatorDigiCareCS81XVETManual external defibrillator
Fendivia 100 µg/hTakedaNC. 658524.5Fentanyl transdermal patch
Guidewire Introducer Needle 18 G x 7 cmArgonGWI1802Introducer needle
Heparine 1%ROVINC. 641647.1Heparin
Hi-Torque VersaTurn FAbbott1013317J0.014-inch 200 cm Guidewire
IsoFloZoetis50019100Isoflurane
KetamidorRichter Pharma AG,NC. 580393.7Ketamine
Lidocaine 50 mg/mLB.BraunNC. 645572.2Lidocaine
MD8000vetMeditech EquipmentMD8000vetMulti-parameter monitor
MidazolamLaboratorios NormonNC. 624437.1Midazolam
Prelude.6F.11 cm (4.3").0.035" (0.89 mm).50 cm (19.7").Double Ended.Stainless Steel.6F.16MeritPSI-6F-11-0356F Vascular sheath
Propovet Multidosis 10 mg/mLZoetisNC. 579742.7Propofol
RENEGADE STC-18 150/20/STRAIGHT/1ROBoston ScientificM001181370150 cm length with 0.017-inch inner diameter Microcatheter
RuschelitTeleflex112482Endotracheal tube with balloon (#6.5)
SPUR IIAmbu325 012 000Airway mask bag unit-ventilation (AMBU)
Vasofix 20 GB.Braun426909820 G Cannula
Visipaque 320 mg/mL USB 10 x 200 mLGeneral Electrics1177612Iodinated contrast medium
VortX-18 Diamond 3 mm/3.3 mmBoston ScientificM0013822030Coil
WATO EX-35MindrayWATO EX-35VetAnesthesia machine

References

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  1. Khan, M., et al. Global epidemiology of ischemic heart disease: Results from the global burden of disease study. Cureus. 12 (7), 9349(2020).
  2. Bhatt, A. S., Ambrosy, A. P., Velazquez, E. J. Adverse remodeling and reverse remodeling after....

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Tags

Myocardial InfarctionSwine ModelCoil DeploymentPercutaneous EmbolizationCoronary AngiographyLeft Ventricular RemodelingCoronary Artery OcclusionFluoroscopic GuidanceAnimal Model MICardiac Magnetic Resonance

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