Name: primary outcome assessment in a pig model of acute myocardial infarction
Uploaded: 2016-10-14T15:00:00
Description: Watch this Scientific Journal Video about Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction at JoVE.com

The authors gratefully acknowledge Marlijn Jansen, Joyce Visser, Grace Croft, Martijn van Nieuwburg, Danny Elbersen and Evelyn Velema for their excellent technical support during the animal experiments.

Toutes les expériences sur les animaux ont été approuvés par le Comité d&#39;éthique sur l&#39;expérimentation animale de l&#39;Université Medical Center Utrecht (Utrecht, Pays-Bas) et sont conformes à la «Guide pour les soins et l&#39;utilisation des animaux de laboratoire». NOTE: Le protocole pour effectuer un ballon d&#39; occlusion fermée thoracique ne fait pas partie du manuscrit en cours et est décrit en détail ailleurs 5. En bref, les porcs (60 - 70 kg) sont s...

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Remodelage cardiaque est en grande partie en fonction de la taille de l&#39; infarctus du myocarde et de la qualité de l&#39; infarctus du myocarde réparer 6,26. Pour évaluer l&#39;ancien d&#39;une manière standardisée, le présent manuscrit fournit une méthode élégante de perfusion in vivo de bleu Evans combiné avec ex vivo TTC coloration, qui a été validé et largement utilisé 8,16,27,28. Cette méthode permet la quantification de la zone à risque (AAR) et la taille...

L&#39; insuffisance cardiaque avec une fraction d&#39;éjection réduite (HFrEF) représente environ 50% de tous les cas d&#39;insuffisance cardiaque, qui touche environ 1 - 2% des personnes dans le monde occidental 1. Sa cause la plus fréquente est l&#39;infarctus du myocarde aigu (AMI). Comme la mortalité aiguë après un IAM a considérablement diminué en raison de la sensibilisation accrue et l&#39;amélioration des options de traitement, l&#39;accent a évolué vers ses séquelles chroniques; l&#39;être le plus important HFrEF 2,3. Avec l&#39; augmentation des coûts de soins de santé 4, l&#39;épidémie croissante de l&#39; insuffisance cardiaque souligne la nécessité de nouveaux diagnostics et thérapies qui peuvent être étudiés dans un modèle porcin hautement traductionnelle de remodelage indésirable après AMI comme décrit précédemment 5. Les deux, les déterminants (par exemple, la taille de l&#39; infarctus) et fonctionnelles des évaluations (par exemple, échocardiographie) du remodelage défavorable sont souvent utilisés pour les tests d&#39;efficacité de nouveaux traitements, ce qui indique la nécessité de relméthodes iable et relativement peu coûteux. L&#39;objectif du présent document est de répondre à ce besoin en introduisant des mesures de résultats importants et fiables pour les tests d&#39;efficacité dans un modèle porcin de l&#39;infarctus du myocarde aigu. Ceux-ci comprennent la taille de l&#39;infarctus (IS) par rapport à la zone à risque (AAR), 3D échocardiographie transœsophagienne (3D-TEE) et pression-volume sur la base d&#39;admission détaillé (PV) acquisition de la boucle. La taille de l&#39; infarctus est le principal déterminant de remodelage défavorable et de survie après AMI 6. Bien que la reperfusion en temps opportun de myocarde ischémique peut sauver cardiomyocytes réversiblement blessés et de limiter la taille de l&#39; infarctus, la reperfusion elle - même provoque des dégâts supplémentaires par la génération de stress oxydatif et une réponse inflammatoire disproportionnée (ischémie-reperfusion (IRI)) 7. Par conséquent, IRI a été identifié comme une cible thérapeutique prometteuse. La capacité des nouveaux traitements pour réduire la taille de l&#39;infarctus est quantifiée en évaluant la taille de l&#39;infarctus par rapportà la zone à risque (AAR). AAR quantification est obligatoire pour corriger la variabilité inter-individuelle dans l&#39;anatomie coronaire de modèles animaux, comme une plus grande AAR mène à une plus grande taille de l&#39;infarctus absolu. Depuis la taille de l&#39; infarctus est directement liée à la performance cardiaque et de la contractilité du myocarde, les variations de l&#39; AAR peuvent influer sur l&#39; étude des mesures de résultats , indépendamment des modalités de traitement 8. échocardiographie transoesophagienne en trois dimensions (3D-TEE) est une méthode peu coûteuse sûre, fiable et, surtout, cliniquement applicable pour mesurer la fonction cardiaque non invasive. Considérant que échocardiographie transthoracique (TTE) images sont limitées à 2D à long et à court parasternale axe vues chez les porcs 9, 3D-TEE peut être utilisé pour obtenir des images complètes en 3 dimensions du ventricule gauche. Par conséquent, il ne nécessite pas des approximations mathématiques du ventricule gauche (LV) volumes tels que la règle de Simpson modifiée 10. Celui-ci est loin de correstimer ectement volumes LV après le remodelage du VG en raison de l&#39;absence de géométrie cylindrique 11. De plus, 3D-TEE est préférable à l&#39; échocardiographie épicardique car il ne nécessite pas d&#39; interventions chirurgicales, qui ont été observés pour exercer des effets cardioprotecteurs dans le modèle actuel 12. Bien que l&#39;utilisation de la 2D-TEE pour l&#39;évaluation de la fonction myocardique a été décrite avant 13,14, les limitations concernant la géométrie du ventricule sont similaires à ceux observés en 2D-TTE et dépendent de l&#39;étendue de remodelage du VG. Par conséquent, plus le Infarctus (et donc plus la probabilité d&#39;une insuffisance cardiaque), les mesures 2D plus susceptibles deviennent viciée par des hypothèses géométriques erronées et plus le besoin de techniques 3D. Néanmoins, la plupart des modalités d&#39;imagerie sont limitées dans leur capacité à évaluer les propriétés fonctionnelles intrinsèques du myocarde. PV boucles fournir de telles informations supplémentaires pertinentes et leur acquisition est doncdécrit en détail ci-dessous.

<table border="0" cellpadding="0" cellspacing="0" width="875">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">3-dimensional transesophageal echocardiography</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
			<td style="width:191px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">iE33 ultrasound device</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">X7-2t transducer</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Aquasonic&#174; 100 ultrasound transmission gel</td>
			<td style="width:180px;">Parker Laboratories Inc.</td>
			<td style="width:108px;">01-34</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Battery handle type C (laryngoscope handle)</td>
			<td style="width:180px;">Riester</td>
			<td style="width:108px;">12303</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Ri-Standard Miller blade MIL 4 (laryngoscope blade)</td>
			<td style="width:180px;">Riester</td>
			<td style="width:108px;">12225</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Qlab 10.0 (3DQ Advanced) analysis software</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Pressure-volume loop acquisition</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Cardiac defibrillator</td>
			<td style="width:180px;">Philips</td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">0.9% saline</td>
			<td style="width:180px;">Braun</td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">8F Percutaneous Sheath Introducer Set</td>
			<td style="width:180px;">Arrow</td>
			<td style="width:108px;">CP-08803</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">9F Radifocus&#174; Introducer II Standard Kit&#160;</td>
			<td style="width:180px;">Terumo</td>
			<td>RS*A90K10SQ</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">8F Fogarty catheter</td>
			<td style="width:180px;">Edward Life Sciences</td>
			<td>62080814F</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7F Criticath&#8482; SP5107H TD catheter (Swan-Ganz)</td>
			<td style="width:180px;">Becton Dickinson (BD)</td>
			<td>680078</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:397px;">Ultraview SL Patient Monitor and Invasive Command Module (external cardiac output device)</td>
			<td>Spacelabs Healthcare</td>
			<td>91387</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">ADVantage system&#8482;</td>
			<td>Transonic SciSense</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7F tetra-polar admittance catheter (7.0 VSL Pigtail / no lumen)</td>
			<td>Transonic SciSense</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Multi-channel acquisition system (Iworx 404)</td>
			<td>Iworx</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Labscribe V2.0 analysis software</td>
			<td style="width:180px;">Iworx</td>
			<td style="width:108px;">-</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Name</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Infarct size / area-at-risk quantification</td>
			<td style="width:180px;"></td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Diathermy</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Lebsch knife</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Hammer</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Bone marrow wax</td>
			<td style="width:180px;">Syneture</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Klinkenberg scissors</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Retractor</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Surgical scissors</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">7F Percutaneous Sheath Introducer Set&#160;</td>
			<td style="width:180px;">Arrow</td>
			<td>CP-08703</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">8F Percutaneous Sheath Introducer Set&#160;</td>
			<td style="width:180px;">Arrow</td>
			<td style="width:108px;">CP-08803</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">7F JL4 guiding catheter&#160;</td>
			<td style="width:180px;">Boston Scientific</td>
			<td style="width:108px;">H749 34357-662</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">8F JL4 guiding catheter&#160;</td>
			<td style="width:180px;">Boston Scientific</td>
			<td>H749 34358-662&#160;</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">COPILOT Bleedback Control Valves&#160;</td>
			<td>Abbott Vascular</td>
			<td>1003331</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">BD Connecta&#8482;&#160;</td>
			<td style="width:180px;">Franklin Lakes</td>
			<td>394995</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Contrast agent</td>
			<td style="width:180px;">Telebrix</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:397px;">Persuader 9 Steerable Guidewire 9 (0.014&#34;, 180 cm, straight tip), hydrophilic coating</td>
			<td style="width:180px;">Medtronic Inc.</td>
			<td>9PSDR180HS</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:397px;">SAPPHIRE&#8482; Coronary Dilatation Catheter (PTCA balloon suitable for the size of the particular coronary artery (2.75 - 3.25 mm))</td>
			<td style="width:180px;">OrbusNeich</td>
			<td style="width:108px;">103-3015</td>
			<td>Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Evans Blue&#160;</td>
			<td style="width:180px;">Sigma-Aldrich</td>
			<td>E2129-100G</td>
			<td>Toxic. Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">2,3,5-triphenyl-tetrazolium chloride (TTC)</td>
			<td style="width:180px;">Sigma-Aldrich</td>
			<td>T8877-100G</td>
			<td>Irritant. Alternative product can be used</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">9V battery</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Ruler</td>
			<td style="width:180px;">-</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:397px;">Photocamera</td>
			<td style="width:180px;">Sony</td>
			<td style="width:108px;">-</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:397px;">ImageJ</td>
			<td style="width:180px;">National Institutes of Health</td>
			<td style="width:108px;">-</td>
			<td>Alternative product can be used</td>
		</tr>
	</tbody>
</table>

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.

<html> 3D échocardiographie transœsophagienne 3D échocardiographie transoesophagienne (3D-TEE) peut être utilisé pour l&#39;évaluation de la fonction cardiaque globale. Après AMI, la fonction cardiaque globale diffère de valeurs de référence en bonne santé. En particulier, la fraction d&#39;éjection du ventricule gauche (FEVG) diminue de 59 ± 4% à 37 ± 6% après une semaine de reperfusion (n = 10...

Watch this Scientific Journal Video about Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction at JoVE.com

Primary Outcome Assessment in a Pig Model of Acute Myocardial Infarction

l&#39;évaluation des résultats fiables et précis est la clé pour la traduction des thérapies précliniques dans le traitement clinique. Le présent document décrit comment évaluer trois paramètres de résultats primaires cliniquement pertinents de la performance cardiaque et des lésions dans un modèle d&#39;infarctus du myocarde aigu de porc.

Évaluation des résultats primaires dans un modèle porcin de infarctus aigu du myocarde

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

Research

JoVE Journal

Medicine

Acute Myocardial Infarction in Rats

Infarctus aigu du myocarde chez le rat

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

Recherche

Médecine

MRI and PET in Mouse Models of Myocardial Infarction

IRM et la TEP dans les modèles de souris de l&#39;infarctus du myocarde

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

Myocardial Infarction and Functional Outcome Assessment in Pigs

Infarctus du myocarde et d&#39;évaluation fonctionnelle de résultats chez le porc

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

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Infarctus du myocarde chez les souris néonatales, Un modèle de régénération cardiaque

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 ...

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Analyse en temps réel la pression-volume de l’infarctus aigu du myocarde chez la souris

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...

Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease

PCR numérique pour quantifier les microARN dans l’infarctus aigu du myocarde et les maladies cardiovasculaires en circulation

Circulating serum microRNAs (miRNAs) have shown promise as biomarkers for the cardiovascular disease and acute myocardial infarction (AMI), being released ...

Implantation of hiPSC-derived Cardiac-muscle Patches after Myocardial Injury in a Guinea Pig Model

Implantation des dérivés hiPSC myocarde patchs après lésion myocardique dans un modèle de cochon d’Inde

Due to the limited regeneration capacity of the heart in adult mammals, myocardial infarction results in an irreversible loss of cardiomyocytes. This loss ...

A Cryoinjury Model to Study Myocardial Infarction in the Mouse

Un modèle cryo-blessure pour étudier l'infarctus du myocarde chez la souris

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

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

Transplantation intramyocardique d’hydrogels injectables à chargement MSC après l’infarctus du myocarde dans un modèle murin

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

Utilizing Percutaneous Ventricular Assist Devices in Acute Myocardial Infarction Complicated by Cardiogenic Shock

Utilisation de dispositifs d’assistance ventriculaire percutanée dans l’infarctus aigu du myocarde compliqué par un choc cardiogénique

Cardiogenic shock is defined as persistent hypotension, accompanied by evidence of end organ hypo-perfusion. Percutaneous ventricular assist devices ...