Ces travaux ont été soutenus par des subventions de la National Natural Science Foundation of China (81770271; à Y, Liao), des Fonds conjoints de la National Natural Science Foundation of China (U1908205; à Y, Liao) et des Projets municipaux de planification de la technologie scientifique de Guangzhou (201804020083; au Dr Liao).

Toutes les procédures ont été effectuées selon les lignes directrices sur les soins et l’utilisation des animaux de laboratoire publiées par les National Institutes of Health des États-Unis (publication n° 85-23 des NIH, révisée en 1996). Des souris mâles C57BL/6J (8-10 semaines, 20-25 g) ont été fournies par le Centre animal de l’université médicale du sud.
1. Préparation préopératoire
<ol><li>Pincez la pointe d’une aiguille de 25 G avec un porte-aiguille et émoussé avec un objet dur comme le support.</li>
	<li>Passez une suture absorbable 5-0 à travers l’aiguille, puis courbez-la à 90° avec un support13. REMARQUE : Selon différentes fins de recherche, les chercheurs pourraient sélectionner des lignées absorbables avec un temps d’absorption différent. Dans ce protocole, nous avons utilisé une suture absorbable de 2 semaines pour resserrer l’arc aortique.</li>
	<li>Courbez une autre aiguille de 25 G à 120° et lissez la pointe avec un support à utiliser comme espaceur dans l’étape de ligature. NOTE : Une aiguille de 25 G a été employée comme espaceur pour des souris ayant le poids corporel (BW) et gt;25 g. Utilisez une aiguille de 26 G pour les souris ayant 19-24 g BW.</li>
	<li>Désinfecter le site opératoire avec 75% d’alcool.</li>
	<li>Réglez la température du coussin chauffant à 37 °C.</li>
	<li>Préparer des instruments chirurgicaux stérilisés (y compris 1 ciseaux ophtalmiques, 1 micro ciseaux, 2 pinces à coude microchirurgical, 1 porte-aiguilles et 1 micro porte-aiguilles).</li>
</ol>2. Induction de l’anesthésie et du rasage
<ol><li>Anesthésier une souris par injection intrapénitale d’un mélange de xylazine (5 mg/kg) et de kétamine (100 mg/kg) dilué dans une solution saline (0,9% de NaCl). Confirmez l’anesthésie complète avec le réflexe négatif de retrait de la pédale.</li>
	<li>Gardez la souris en position supine en fixant les incisives avec une suture et en fixant les membres avec des rubans adhésifs.</li>
	<li>Appliquer de la crème depilatory pour enlever les cheveux sur son cou et xiphoïde. Désinfecter la zone avec de l’iode suivi de 75% d’alcool.</li>
</ol>3. Chirurgie
<ol><li>Faire une incision de plus de 10 mm à la position médiane entre l’encoche supra-sternale et la poitrine avec un scalpel. Ensuite, séparez la peau et le fascia superficiel.</li>
	<li>Identifiez le premier espace intercostal en comptant les côtes de l’angle sternal. Effectuez l’incision dans le premier espace intercostal et aussi près que possible du sternum. Pénétrer brutalement avec des pinces à coude pour ouvrir cet espace.</li>
	<li>Séparez doucement le parenchyme et le thymus jusqu’à ce que l’arc aortique transversaux soit visible. REMARQUE : N’endommagez pas la plèvre pariétale pour éviter le pneumothorax.</li>
	<li>Passez la suture absorbable 5-0 sous l’arc aortique entre l’artère brachiocéphale et l’artère carotide commune gauche avec une aiguille de loquet14. S’il vous plaît assurez-vous que l’artère brachiocéphale, l’artère carotide commune gauche, et l’artère subclavienne gauche sont visibles dans le champ d’opération.</li>
	<li>Placez l’espaceur, préparé à l’étape 1.3, sur l’aorte transversale et effectuez un double nœud sur l’espaceur avec la suture à l’étape 3.4. REMARQUE : La pointe de l’espaceur doit être émoussée pour éviter d’endommager l’aorte transversale tout en l’enlevant.</li>
	<li>Retirer l’espaceur rapidement mais doucement, puis couper les extrémités de la suture.</li>
	<li>Fermez le premier espace intercostal et la peau à l’aide de sutures en nylon 5-0. Désinfecter la peau à nouveau avec 75% d’alcool.</li>
	<li>Placez la souris sur le coussin chauffant pour favoriser la récupération. Injecter de la buprénorphine (0,1 mg/kg, q12h) par voie intrapénithique pendant les 3 premiers jours suivant la chirurgie.</li>
	<li>Retournez la souris dans la cage dans une salle de cycle lumière/obscurité de 12 h lorsqu’elle récupère sa conscience.</li>
	<li>Effectuer une chirurgie simulée identique à toutes les étapes ci-dessus, mais sans la constriction (étape 3.5).</li>
	<li>Effectuez une chirurgie pour le groupe de suture de soie, identique à toutes les étapes ci-dessus, mais en utilisant une suture de soie 5-0 dans l’étape 1.2.</li>
</ol>4. Évaluation échocardiographique de la ligature et des mesures réussies
<ol><li>Effectuer une évaluation échocardiographique le jour (D) 7 après la chirurgie.</li>
	<li>Anesthésier la souris avec 3% d’isoflurane par inhalation pour l’induction, et 1,5% pour maintenir la profondeur de l’anesthésie, avec un taux de flux d’oxygène de 0,5-1 L/min.</li>
	<li>Placez la souris en position supinée sur la plate-forme, maintenue à 37 °C, et collez ses membres à l’électrode.</li>
	<li>Retirer les poils de la poitrine avec une crème depilatory et appliquer un agent de couplage ultrasonique sur la poitrine de la souris.</li>
	<li>Évaluer la constriction aortique transversale à l’l’œil d’une sonde de 30 MHz.<ol>
<li>Inclinez la plate-forme à l’extrême gauche. Gardez la sonde en position verticale et abaissez-la sur la poitrine le long de la ligne parasternale droite. Ensuite, manipulez l’axe X et l’axe Y sous mode B jusqu’à ce que l’arc aortique soit clairement visible.</li>
		<li>Localisez la constriction par mode B pour obtenir la vue aortique de l’arc11. Utilisez le mode Doppler couleur et l’onde pulsée pour mesurer la vitesse de débit maximale et sélectionnez des souris avec une vitesse de plus de 3 000 mm/s comme groupe TAC (les valeurs sont basées sur des expériences préliminaires).</li>
		<li>Calculez le gradient de pression selon la version modifiée de l’équation11 deBernoulli : gradient de pression = 4 x Vmax2. REMARQUE : Le gradient de pression idéal pour le modèle de constriction aortique transversale varie de 40 à 80 mmHg11.</li>
		<li>Enregistrez les données et les images à l’aide de Cine Store et Frame Store.</li>
	</ol>
</li>
	<li>Évaluer les dimensions et la contractilité du ventriculaire gauche (LV) à l’œil d’une sonde de 30 MHz.<ol>
<li>Réinitialisez la plate-forme à la position horizontale. Gardez la sonde à 30° dans le sens inverse des aiguilles d’une montre par rapport à la ligne parasternale gauche.</li>
		<li>Utilisez le mode B et manipulez X et Y pour obtenir une vue d’axe claire et pleine-longue du coeur.</li>
		<li>Appuyez sur le mode M pour afficher la ligne d’indicateur. Obtenez des images avec Cine Store et Frame Store pour une mesure ultérieure de la dimension de chambre LV, du raccourcissement fractionnel et de l’épaisseur du mur LV.</li>
	</ol>
</li>
	<li>Une fois fait, arrêter l’inhalation d’isoflurane et permettre à la souris de récupérer de l’anesthésie. Ensuite, retournez l’animal dans sa cage dans une salle de cycle clair/sombre de 12 h.</li>
	<li>Sur D14 et D28 après la chirurgie, répétez les étapes ci-dessus pour mesurer les paramètres cardiaques, puis récoltez le cœur pour des études histologiques.</li>
</ol>

<ol>
	<li>Murry, C. E., Jennings, R. B., Reimer, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preconditioning+with+ischemia:+a+delay+of+lethal+cell+injury+in+ischemic+myocardium.">Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.</a> Circulation. 74 (5), 1124-1136 (1986).</li><li>Ban, K., 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=Phosphatidylinositol+3-kinase+gamma+is+a+critical+mediator+of+myocardial+ischemic+and+adenosine-mediated+preconditioning.">Phosphatidylinositol 3-kinase gamma is a critical mediator of myocardial ischemic and adenosine-mediated preconditioning.</a> Circulation Research. 103 (6), 643-653 (2008).</li><li>Wu, Z. K., Iivainen, T., Pehkonen, E., Laurikka, J., Tarkka, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ischemic+preconditioning+suppresses+ventricular+tachyarrhythmias+after+myocardial+revascularization.">Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization.</a> Circulation. 106 (24), 3091-3096 (2002).</li><li>Hausenloy, D. J., Yellon, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preconditioning+and+postconditioning:+underlying+mechanisms+and+clinical+application.">Preconditioning and postconditioning: underlying mechanisms and clinical application.</a> Atherosclerosis. 204 (2), 334-341 (2009).</li><li>Heusch, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+basis+of+cardioprotection:+signal+transduction+in+ischemic+pre-,+post-,+and+remote+conditioning.">Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning.</a> Circulation Research. 116 (4), 674-699 (2015).</li><li>Lund, O., Emmertsen, K., Dorup, I., Jensen, F. T., Flo, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regression+of+left+ventricular+hypertrophy+during+10+years+after+valve+replacement+for+aortic+stenosis+is+related+to+the+preoperative+risk+profile.">Regression of left ventricular hypertrophy during 10 years after valve replacement for aortic stenosis is related to the preoperative risk profile.</a> European Heart Journal. 24 (15), 1437-1446 (2003).</li><li>Rockman, H. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Segregation+of+atrial-specific+and+inducible+expression+of+an+atrial+natriuretic+factor+transgene+in+an+in+vivo+murine+model+of+cardiac+hypertrophy.">Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.</a> Proceedings of the National Academy of Sciiences of the United States of America. 88 (18), 8277-8281 (1991).</li><li>Wei, X., 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=Myocardial+hypertrophic+preconditioning+attenuates+cardiomyocyte+hypertrophy+and+slows+progression+to+heart+failure+through+upregulation+of+S100A8/A9.">Myocardial hypertrophic preconditioning attenuates cardiomyocyte hypertrophy and slows progression to heart failure through upregulation of S100A8/A9.</a> Circulation. 131 (17), 1506-1517 (2015).</li><li>Huang, J., 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=Ultrasound+biomicroscopy+validation+of+a+murine+model+of+cardiac+hypertrophic+preconditioning:+comparison+with+a+hemodynamic+assessment.">Ultrasound biomicroscopy validation of a murine model of cardiac hypertrophic preconditioning: comparison with a hemodynamic assessment.</a> American Journal of Physiology. 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(112), e54101 (2016).</li><li>Veldhuizen, R. A., Slutsky, A. S., Joseph, M., McCaig, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+mechanical+ventilation+of+isolated+mouse+lungs+on+surfactant+and+inflammatory+cytokines.">Effects of mechanical ventilation of isolated mouse lungs on surfactant and inflammatory cytokines.</a> The European Respiratory Journal. 17 (3), 488-494 (2001).</li><li>Wang, Q., 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=Induction+of+right+ventricular+failure+by+pulmonary+artery+constriction+and+evaluation+of+right+ventricular+function+in+mice.">Induction of right ventricular failure by pulmonary artery constriction and evaluation of right ventricular function in mice.</a> Journal of Visualized Experiments. 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Les auteurs n’ont rien à divulguer.

Il y a encore un secteur largement sous-explosé dans le préconditionnement non ischémique cardiaque. Sur la base de nos études précédentes, nous sommes passés à l’utilisation de sutures absorbables pour améliorer le modèle de préconditionnement hypertrophique myocardique.
Dans les rapports précédents, de nombreux chercheurs ont utilisé la suture de soie pour resserrer l’arc aortique8,14,15...

La conditionnement ischémique est un phénomène qui induit de brefs épisodes non létaux d’ischémie et de reperfusion au cœur et a la capacité de réduire considérablement les lésions myocardiques1. Compte tenu des implications cliniques évidentes du préconditionnement ischémique, tels que la limitation de la taille infarctus du myocarde2 et la suppression des tachyarrhythmies ventriculaires après la revascularisation myocardique3, il y a eu beaucoup de recherche pour disséquer les mécanismes sous-jacents aux effets cardio-protecteurs induits par la conditionpréalable 4,5. En revanche, d’autres types non ischémiques de condition préalable ont reçu relativement peu d’attention. L’hypertrophie cardiaque peut être émoussée dans les patients présentant la sténose aortique subissant le remplacement aortique de valve6. Partout où l’état de l’hypertrophie myocardique pathologique existe, le principe de la condition préalable est rarement rapporté.
En 1991, Rockman et coll. ont d’abord établi un modèle muran d’hypertrophie ventriculaire gauche par constriction aortique transversale (TAC)7. En activant le TAC deux fois chez la souris, nous avons précédemment prouvé que le préconditionnement hypertrophique myocardique (MHP) mène à la stimulation hypertrophique passagère dans le coeur rendant ainsi le coeur plus résistant au stress hypertrophique soutenu dans lefutur 8. Les caractéristiques du modèle MHP ont été validées par échographie biomicroscope et évaluation hémodynamique9. Les points clés dans la construction du modèle a été d’effectuer la thoracotomie trois fois, TAC pendant une semaine, la bande pendant une semaine, et tac secondaire pendant 6 semaines. Cependant, la bande pourrait causer des saignements, ce qui rend difficile d’être maîtrisé par les novices et difficile à populariser. En outre, c’est aussi un défi technique d’intuber les souris. Une intubation inappropriée pourrait causer des lésions trachées, du pneumothorax et même la mort chez la souris. Ainsi, il est nécessaire et précieux d’améliorer certaines procédures lors de la construction du modèle MHP.
Pour réduire la difficulté du modèle et augmenter son succès, nous sommes passés à des sutures absorbables pour le premier TAC et avons surveillé le succès du modèle en mesurant le gradient de pression à travers la constriction aortique sous échocardiographie10. Sur la base de notre expérience préliminaire, il serait difficile d’induire une hypertrophie myocardique suffisante chez les souris ayant un gradient de pression trop faible, tandis que les souris avec un gradient de pression trop élevée développeraient une insuffisance cardiaque aiguë ou même mourraient. Le gradient de pression idéal pour le modèle varie de 40-80 mmHg11. En outre, cette expérience ne s’est pas fiée à un ventilateur, qui pourrait effectivement éviter la manipulation technique et les blessures associées auventilateur 12.

<table>
	<tbody>
		<tr>
			<td>Absorbable suture (5-0)</td>
			<td>Shandong Kang Lida Medical Products Co., Ltd</td>
			<td>5-0</td>
			<td>Ligation</td>
		</tr>
		<tr>
			<td>Animal ultrasound system VEVO2100</td>
			<td>Visual Sonic</td>
			<td>VEVO2100</td>
			<td>Echocardiography</td>
		</tr>
		<tr>
			<td>Cold light illuminator</td>
			<td>Olympus</td>
			<td>ILD-2</td>
			<td>Light</td>
		</tr>
		<tr>
			<td>Heat pad- thermostatic surgical system (ALC-HTP-S1)</td>
			<td>SHANGHAI ALCOTT BIOTECH CO</td>
			<td>ALC-HTP-S1</td>
			<td>Heating</td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>RWD life science</td>
			<td>R510-22</td>
			<td>Inhalant anaesthesia</td>
		</tr>
		<tr>
			<td>Matrx VIP 3000 Isofurane Vaporizer</td>
			<td>Midmark Corporation</td>
			<td>VIP 3000</td>
			<td>Anesthetization</td>
		</tr>
		<tr>
			<td>Medical nylon suture (5-0)</td>
			<td>Ningbo Medical Needle Co.</td>
			<td>5-0</td>
			<td>Close the skin</td>
		</tr>
		<tr>
			<td>Pentobarbital sodium salt</td>
			<td>Merck</td>
			<td>25MG</td>
			<td>Anesthetization</td>
		</tr>
		<tr>
			<td>Precision electronic balance</td>
			<td>Denver Instrument</td>
			<td>TB-114</td>
			<td>Weighing sensor</td>
		</tr>
		<tr>
			<td>Self-made spacer</td>
			<td></td>
			<td></td>
			<td>25-gauge needle</td>
		</tr>
		<tr>
			<td>Silk suture (5-0)</td>
			<td>Yangzhou Yuankang Medical Devices Co., Ltd.</td>
			<td>5-0</td>
			<td>Ligation</td>
		</tr>
		<tr>
			<td>Small animal microsurgery equipment</td>
			<td>Napox</td>
			<td>MA-65</td>
			<td>Surgical instruments</td>
		</tr>
		<tr>
			<td>Transmission Gel</td>
			<td>Guang Gong pai</td>
			<td>250ML</td>
			<td>Echocardiography</td>
		</tr>
		<tr>
			<td>Veet hair removal cream</td>
			<td>Reckitt Benchiser</td>
			<td>RQ/B 33 Type 2</td>
			<td>Remove hair of mice</td>
		</tr>
		<tr>
			<td>Vertical automatic electrothermal pressure steam sterilizer</td>
			<td>Hefei Huatai Medical Equipment Co.</td>
			<td>LX-B50L</td>
			<td>Auto clean the surgical instruments</td>
		</tr>
	</tbody>
</table>

operating transverse aortic constriction with absorbable suture to obtain transient myocardial hypertrophy

Basé sur des constrictions aortiques deux fois transversales (TACs) chez la souris, il est prouvé que le préconditionnement hypertrophique myocardique (MHP) pourrait atténuer l’hypertrophie cardiomyocyte et ralentir la progression à l’insuffisance cardiaque. Pour les novices, cependant, le modèle MHP est généralement assez difficile à établir en raison des obstacles techniques dans le fonctionnement du ventilateur, l’ouverture de la poitrine à plusieurs reprises, et les saignements causés par la bande. Pour faciliter ce modèle, pour augmenter le taux de réussite chirurgicale et pour réduire l’incidence des saignements, nous sommes passés à des sutures absorbables pour le premier peignage TAC avec une technique sans ventilateur. Utilisant une suture absorbable de 2 semaines, nous avons démontré que cette procédure pourrait causer l’hypertrophie myocardique significative en 2 semaines ; et 4 semaines après chirurgie, l’hypertrophie myocardique a été presque complètement régressée à la ligne de base. En utilisant ce protocole, les opérateurs pourraient maîtriser facilement le modèle MHP avec une mortalité de fonctionnement plus faible.

Dans cette étude, nous avons divisé au hasard 45 souris en trois groupes, la feinte, le groupe de suture de soie, et le groupe absorbable de suture (le nombre de chaque groupe sur D0 (ligne de base), D14, et D28 après TAC était 15, 10, et 5, respectivement). Sur D7, D14, D21, et D28 après la chirurgie, la vitesse de pointe resserrée a été déterminée par échocardiographie. Nous avons constaté que la vitesse du flux sanguin à la constriction était encore supérieure à 3 000 mm/s dans la deuxième semaine sui...

Watch this Scientific Journal Video about Operating Transverse Aortic Constriction with Absorbable Suture to Obtain Transient Myocardial Hypertrophy at JoVE.com

Operating Transverse Aortic Constriction with Absorbable Suture to Obtain Transient Myocardial Hypertrophy

Ce protocole présente une méthode améliorée pour obtenir l’hypertrophie myocardique passagère avec la suture absorbable, simulant la diminution ventriculaire gauche d’hypertrophie après avoir enlevé la surcharge de pression. Il pourrait être utile pour les études sur le préconditionnement hypertrophique myocardique.

Exploitation de la constriction aortique transversale avec suture absorbable pour obtenir une hypertrophie myocardique transitoire

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate ...

operating-transverse-aortic-constriction-with-absorbable-suture-to

Research

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Medicine

6.1K vues.  Southern Medical University. Ce protocole présente une méthode améliorée pour obtenir l’hypertrophie myocardique passagère avec la suture absorbable, simulant la diminution ventriculaire gauche d’hypertrophie après avoir enlevé la surcharge de pression. Il pourrait être utile pour les études sur le préconditionnement hypertrophique myocardique.

Vidéo: Operating Transverse Aortic Constriction with Absorbable Suture to Obtain Transient Myocardial Hypertrophy

A Research Method For Detecting Transient Myocardial Ischemia In Patients With Suspected Acute Coronary Syndrome Using Continuous ST-segment Analysis

Each year, an estimated 785,000 Americans will have a new coronary attack, or acute coronary syndrome (ACS). The pathophysiology of ACS involves rupture of an atherosclerotic plaque; hence, treatment is aimed at plaque stabilization in order to prevent cellular death. However, there is considerable debate among clinicians, about which treatment pathway is best: early invasive using percutaneous coronary intervention (PCI/stent) when indicated or a conservative approach (i.e., medication only with PCI/stent if recurrent symptoms occur).
There are three types of ACS: ST elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI), and unstable angina (UA). Among the three types, NSTEMI/UA is nearly four times as common as STEMI. Treatment decisions for NSTEMI/UA are based largely on symptoms and resting or exercise electrocardiograms (ECG). However, because of the dynamic and unpredictable nature of the atherosclerotic plaque, these methods often under detect myocardial ischemia because symptoms are unreliable, and/or continuous ECG monitoring was not utilized.
Continuous 12-lead ECG monitoring, which is both inexpensive and non-invasive, can identify transient episodes of myocardial ischemia, a precursor to MI, even when asymptomatic. However, continuous 12-lead ECG monitoring is not usual hospital practice; rather, only two leads are typically monitored. Information obtained with 12-lead ECG monitoring might provide useful information for deciding the best ACS treatment.
Purpose. Therefore, using 12-lead ECG monitoring, the COMPARE Study (electroCardiographic evaluatiOn of ischeMia comParing invAsive to phaRmacological trEatment) was designed to assess the frequency and clinical consequences of transient myocardial ischemia, in patients with NSTEMI/UA treated with either early invasive PCI/stent or those managed conservatively (medications or PCI/stent following recurrent symptoms). The purpose of this manuscript is to describe the methodology used in the COMPARE Study.
Method. Permission to proceed with this study was obtained from the Institutional Review Board of the hospital and the university. Research nurses identify hospitalized patients from the emergency department and telemetry unit with suspected ACS. Once consented, a 12-lead ECG Holter monitor is applied, and remains in place during the patient's entire hospital stay. Patients are also maintained on the routine bedside ECG monitoring system per hospital protocol. Off-line ECG analysis is done using sophisticated software and careful human oversight.

Continuous 12-lead electrocardiographic (ECG) monitoring can identify transient myocardial ischemia, even when asymptomatic, among patients with suspected acute coronary syndrome (ACS). In this article we describe our method for initiating patient monitoring using a Holter device, downloading the ECG data for off-line analysis, and how to utilize the ECG software to identify transient ischemia.

Une méthode de recherche pour la détection de l&#39;ischémie myocardique transitoire chez les patients présentant une suspicion de syndrome coronarien aigu L&#39;utilisation continue du segment ST analyse

Each year, an estimated 785,000 Americans will have a new coronary attack, or acute coronary syndrome (ACS). The pathophysiology of ACS involves rupture ...

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Médecine

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50&#8211;60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.

We describe a stepwise procedure for creating pressure overload and left ventricular hypertrophy in Wistar rats by constriction of the ascending aorta using a small metallic clip. This model is extensively used for studying remodeling changes during cardiac hypertrophy and for identifying and evaluating strategies for regression of such changes.

Aortique ascendant constriction chez les rats pour la création de la surcharge de pression hypertrophie cardiaque Modèle

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart ...

Murine Isolated Heart Model of Myocardial Stunning Associated with Cardioplegic Arrest

The following protocol is of use to evaluate impaired cardiac function or myocardial stunning following moderate ischemic insults. The technique is useful for modeling ischemic injury associated with numerous clinically relevant phenomenon including cardiac surgery with cardioplegic arrest and cardiopulmonary bypass, off-pump CABG, transplant, angina, brief ischemia, etc. The protocol presents a general method to model hypothermic hyperkalemic cardioplegic arrest and reperfusion in rodent hearts focusing on measurement of myocardial contractile function. In brief, a mouse heart is perfused in langendorff mode, instrumented with an intraventricular balloon, and baseline cardiac functional parameters are recorded. Following stabilization, the heart is then subject to brief infusion of a cardioprotective hypothermic cardioplegia solution to initiate diastolic arrest. Cardioplegia is delivered intermittently over 2 hr. The heart is then reperfused and warmed to normothermic temperatures and recovery of myocardial function is monitored. Use of this protocol results in reliable depressed cardiac contractile function free from gross myocardial tissue damage in rodents.

The goal of this protocol to assess myocardial stunning following ischemic cardioplegic arrest in rodents.

Murin isolé Modèle de Cœur de sidération myocardique liée à l&#39;arrêt cardioplégique

The following protocol is of use to evaluate impaired cardiac function or myocardial stunning following moderate ischemic insults. The technique is useful ...

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function2. Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease.

The goal of this protocol is to noninvasively assess cardiac structural and functional changes in a mouse model of heart disease created by transverse aortic constriction, using B- and M-mode echocardiography and color/pulse wave Doppler imaging.

Évaluation des cardiaques morphologiques et fonctionnelles changements dans le modèle de souris de Transverse Aortic Constriction par échocardiographie Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable ...

Minimally Invasive Transverse Aortic Constriction in Mice

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.

Minimally invasive transverse aortic constriction (MTAC) conserves the essentials of regular transverse aortic constriction (TAC) while eliminating the use of a ventilator with tracheal intubation. It proves to be a highly desirable method for high-throughput studies on left ventricular overload, particularly in translational studies.

Minimalement invasive Transverse Aortic constriction chez la souris

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard ...

Full-root Aortic Valve Replacement by Stentless Aortic Xenografts in Patients with Small Aortic Roots

In patients with small aortic roots who need an aortic valve replacement with biological valve substitutes, the implantation of the stented pericardial valve might not meet the functional needs. The implantation of a too-small stented pericardial valve, leading to an effective orifice area indexed to a body surface area less than 0.85 cm2/m2, is regarded as prosthesis-patient mismatch (PPM). A PPM negatively affects the regression of left ventricular hypertrophy and thus the normalization of left ventricular function and the alleviation of symptoms. Persistent left ventricular hypertrophy is associated with an increased risk of arrhythmias and sudden cardiac death. In the case of predictable PPM, there are three options: 1) accept the PPM resulting from the implantation of a stented pericardial valve when comorbidities of the patient forbid the more technically demanding operative technique of implanting a larger prosthesis, 2) enlarge the aortic root to accommodate a larger stented valve substitute, or 3) implant a stentless biological valve or a homograft. Compared to classical aortic valve replacement with stented pericardial valves, the full-root implantation of stentless aortic xenografts offers the possibility of implanting a 3-4 mm larger valve in a given patient, thus allowing significant reduction in transvalvular gradients. However, a number of cardiac surgeons are reluctant to transform a classical aortic valve replacement with stented pericardial valves into the more technically challenging full-root implantation of stentless aortic xenografts. Given the potential hemodynamic advantages of stentless aortic xenografts, we have adopted full-root implantation to avoid PPM in patients with small aortic roots necessitating an aortic valve replacement. Here, we describe in detail a technique for the full-root implantation of stentless aortic xenografts, with emphasis on the management of the proximal suture line and coronary anastomoses. Limitations of this technique and alternative options are discussed.

Full-root aortic valve replacement by stentless aortic xenograft is a viable option in patients with small aortic roots. We describe, a technique for the full-root implantation of stentless aortic xenografts, with emphasis on the management of the proximal suture line and coronary anastomoses, and discuss its limitations and alternative options.

Remplacement de la vanne aortique à racines complètes par des xénogreffes d&#39;aorte stentless chez des patients ayant de petites racines aortiques

In patients with small aortic roots who need an aortic valve replacement with biological valve substitutes, the implantation of the stented pericardial ...

Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure overload-induced left ventricular hypertrophy (LVH) and its progression to heart failure. In the majority of the reported investigations, this procedure is performed with intubation and ventilation of the animal which renders it demanding and time-consuming and adds to the surgical burden to the animal. The aim of this protocol is to describe a simplified technique of minimally invasive TAC without intubation and ventilation of mice. Critical steps of the technique are emphasized in order to achieve low mortality and high efficiency in inducing LVH.
Male C57BL/6 mice (10-week-old, 25-30 g, n=60) were anesthetized with a single intraperitoneal injection of a mixture of ketamine and xylazine. In a spontaneously breathing animal following a 3-4 mm upper partial sternotomy, a segment of 6/0 silk suture threaded through the eye of a ligation aid was passed under the aortic arch and tied over a blunted 27-gauge needle. Sham-operated animals underwent the same surgical preparation but without aortic constriction. The efficacy of the procedure in inducing LVH is attested by a significant increase in the heart/body weight ratio. This ratio is obtained at days 3, 7, 14 and 28 after surgery (n = 6 - 10 in each group and each time point). Using our technique, LVH is observed in TAC compared to sham animals from day 7 through day 28. Operative and late (over 28 days) mortalities are both very low at 1.7%.
In conclusion, our cost-effective technique of minimally invasive TAC in mice carries very low operative and post-operative mortalities and is highly efficient in inducing LVH. It simplifies the operative procedure and reduces the strain put on the animal. It can be easily performed by following the critical steps described in this protocol.

The aim of this protocol is to describe step-by-step the technique of minimally invasive transverse aortic constriction (TAC) in mice. By elimination of intubation and ventilation which are mandatory for the commonly used standard procedure, minimally invasive TAC simplifies the operative procedure and reduces the strain put on the animal.

Technique mini-Invasive transversal constriction aortique chez les souris pour l’Induction de l’hypertrophie ventriculaire gauche

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to perform a partial thoracotomy to visualize the transverse aortic arch. However, the surgical trauma caused by the thoracotomy in open-chest models changes the respiratory physiology as the ribs are dissected and left unattached after chest closure. To prevent this, we established a minimally invasive, closed chest approach via lateral thoracotomy. Herein we approach the aortic arch via the 2nd intercostal space without entering the chest cavities, leaving the mouse with a less traumatic injury to recover from. We perform this operation using standard laboratory settings for open chest TAC procedures with equal survival rates. Apart from maintaining physiological breathing patterns due to the closed chest approach, the mice seem to benefit by showing rapid recovery, as the less invasive technique appears to facilitate a fast healing process and to reduce immune response after trauma.

Here, we present a protocol of Transverse Aortic constriction (TAC) via a lateral thoracotomy. This technique is a minimally invasive, closed chest surgical procedure aiming to simulate pressure overload and heart failure in mice utilizing standard TAC laboratory settings.

Un modèle à thorax fermé pour induire la Constriction de l’aorte transversale chez les souris

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. However, only minor improvement in the long-term results of transplanted solid organs could be observed over the past decades. In this context, chronic allograft vasculopathy (CAV) still represents the leading cause of late organ failure in cardiac, renal and pulmonary transplantation.
Thus far, the underlying pathogenesis of CAV development remains unclear, explaining why effective treatment strategies are presently missing and emphasizing a need for relevant experimental models in order to study the underlying pathophysiology leading to CAV formation. The following protocol describes a murine heterotopic cervical aortic transplantation model using a modified non-suture cuff technique. In this technique, a segment of the thoracic aorta is interpositioned in the right common carotid artery. With the use of the non-suture cuff technique, an easy to learn and reproducible model can be established, minimizing the possible heterogeneity of sutured vascular micro anastomoses.

Here, we present a protocol of heterotopic aortic transplantation in mice using the non-suture cuff technique in a cervical murine model. This model can be used to study the underlying pathology of chronic allograft vasculopathy (CAV) and can help evaluate new therapeutic agents in order to prevent its formation.

Modèle de transplantation aortique cervicale de Murine utilisant une technique modifiée de manchette de non-suture

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. ...

Using Q Suture to Enhance Resistance to Gap Formation and Tensile Strength of Repaired Flexor Tendons

Peripheral epitendinous sutures are believed to enhance core suture strength in tendon repair and decrease the risk of gapping between tendon ends. Here Q suture, an alternative to peripheral sutures, is presented for the use in tendon repair. Its effects on gap formation and tensile strength of the repaired tendons were compared with conventional running peripheral sutures. Three 2-strand sutures and three 4-strand sutures were used in repairing porcine tendons. The time required for performing 2Q and running sutures were recorded. The repaired tendons were subjected to a cyclic loading test, and the cycle number, during which a 2-mm gap was formed, was determined. After the cyclic loading, the gap size at the tendon ends and the ultimate strength of the repaired tendons were measured. Augmentation with the Q sutures reduced the number of tendons showing 2-mm gaps at tendon ends during cyclic loading. With addition of Q sutures 2-strand sutures significantly increased the ultimate strength of the repaired tendons and 4-strand sutures decreased the gap distance at the repair site of tendons. The time required for performing 2Q sutures was significantly less than that for running sutures. Therefore, we conclude that the Q suture is efficient in enhancing the tensile resistance and tendon repair strength and can be an alternative to conventional peripheral sutures.

Here, we present a &#8220;Q&#8221; suture technique that can be performed in tendon repair and its effects on the gap formation and tensile strength of the repaired tendons. Q suture is shown to be efficient in enhancing the tensile resistance and tendon repair strength.

Utilisation de la suture Q pour renforcer la résistance à la formation d’écart et la résistance à la traction des tendons fléchisseurs réparés

Peripheral epitendinous sutures are believed to enhance core suture strength in tendon repair and decrease the risk of gapping between tendon ends. Here Q ...