This work was supported by Onderzoekstoelagen grant OT/13/090 of the KU Leuven and by grant G0A3114N of the FWO-Vlaanderen.

NOTE: Toutes les procédures expérimentales décrites dans cette section ont été approuvés par la protection des animaux et le Comité consultatif de recherche de la Katholieke Universiteit Leuven institutionnel (projet: 154/2013-B De Geest). 1. La ligature permanente de l&#39;artère interventriculaire antérieure coronaire <ol><li> Anesthésier la souris par administration intraperitoneale de 40 mg / kg à 70 mg / kg de pentobarbital de sodium. Assurez-vous de la souris atteint son bon plan de l&#39;anesthésie quand il ne réagit plus un pincement de l&#39;orteil entreprise. Toujours confirmer anesthésie appropriée de cette façon avant toute procédure ou une intervention chirurgicale. Utilisez pommade ophtalmique lubrifiante pour prévenir la sécheresse de la cornée sous anesthésie. Fournir une analgésie préopératoire 2-4 h avant le début de la procédure (buprénorphine 0,05 mg / kg SQ). <ol><li> Appliquer des techniques aseptiques cohérentes pendant la chirurgie de survie. Mettre en œuvre des procédures qui empêchent à un con microbienne maximum possible de mesurecontamination de sorte que l&#39;infection importante ou suppuration ne se produit pas. Ces procédures comprennent l&#39;utilisation d&#39;instruments stériles et les matériaux stériles, désinfection de la zone chirurgicale, et l&#39;enlèvement des poils / cheveux sur le site chirurgical et la désinfection de ce site. </li></ol></li><li> Intuber la souris avec un émoussé aiguille de calibre 20 auto-préparés. <ol><li> Mettez la souris en position couchée avec hyperextension de la tête. <ol><li> Concentrer la lumière sur la région du cou. Soulevez la langue avec un pincet émoussée. L&#39;entrée du larynx peut être clairement vu. </li><li> Passez l&#39;aiguille émoussée par le larynx dans la trachée sous vision directe. Évaluer correcte intubation en connectant la souris pour le ventilateur (volume de course dans ul: 3 x poids corporel (g) + 155, fréquence: 120 coups par minute). </li></ol></li><li> Alternativement, améliorer la visualisation de l&#39;intubation endotrachéale en exposant d&#39;abord soigneusement la trachée. <ol><li> Faire une incision de 5 mm à mi-cou et se rétracterle tissu musculaire juste au-dessus de la trachée. </li><li> Effectuer l&#39;intubation en utilisant un stéréomicroscope chirurgicale pour la visualisation directe de la trachée. Soulevez la langue et entrez l&#39;aiguille de calibre 20 auto-préparé émoussé dans la trachée. Confirmez intubation en connectant la souris pour le ventilateur (volume de course dans ul: 3 x poids corporel (g) + 155, fréquence: 120 coups par minute). </li></ol></li></ol></li><li> Gardez la souris en position couchée et fixer la souris avec du ruban adhésif. Effectuer une intervention chirurgicale sur un coussin chauffant pour prévenir l&#39;hypothermie. <ol><li> Rasage et désinfecter la peau à la Bétadine. Veillez à ce que la patte postérieure gauche traverse la patte arrière droite afin d&#39;obtenir une meilleure vue sur le ventricule gauche pendant la chirurgie. </li></ol></li><li> Faire une petite incision cutanée jusqu&#39;à transversale du sternum et de séparer la peau et les muscles sous-jacent. </li><li> Tirez de côté le m. pectoral et m. pectoral avec une suture de soie 5-0. </li><li> Faire une incision dans le troisième espace intercostal en insérant un pincet émoussée. </li><li> Déplacez le pincet sous les muscles intercostaux du dehors en dedans jusqu&#39;au sternum est atteint. Perforer la paroi thoracique en appuyant sur le pincet de l&#39;intérieur vers la peau. Remplissez la thoracotomie en coupant le muscle intercostal attentivement juste au-dessus de la pincet avec un petit ciseau. Utiliser cette technique pour empêcher la perforation des poumons. </li><li> Mettre une éponge immergée dans 0,9% de NaCl dans la cavité pour protéger les poumons. Présentez un épandeur de la plaie (la poitrine enrouleur) dans l&#39;espace intercostal pour obtenir une exposition du côté gauche du cœur. A partir de maintenant, l&#39;oreillette gauche, le ventricule gauche et l&#39;artère interventriculaire antérieure coronarienne sont visibles au microscope stéréoscopique. </li><li> Effectuez une ligature de l&#39;artère interventriculaire antérieure coronaire avec un seul 6-0 prolène ligature environ 1 mm sous la pointe de l&#39;oreillette gauche. Ce est distale de la première branche diagonale. REMARQUE: Sinon, 7-0 (00,05 mm de diamètre) ou de fils (8-0 0,04 mm de diamètre) peuvent être utilisés. L&#39;aiguille est une aiguille Point C-1 13 mm 3/8 cercle conique. Ligature réussie de la descendante antérieure gauche artère coronaire induit une décoloration immédiate, résultant dans un myocarde apparaissant pâle sur le territoire concerné. </li><li> Retirez l&#39;épandeur de la plaie (la poitrine de l&#39;enrouleur). <ol><li> Placez trois 6-0 sutures Ti-Cron autour de l&#39;espace intercostal. Avant de serrer les sutures, retirez l&#39;éponge de la cavité de la poitrine et re-développer les poumons en bloquant la sortie du ventilateur. Ce faisant, les poumons renouer avec la plèvre pariétale. </li><li> Ensuite, tirez les sutures serré et répéter ré-expansion en appuyant sur la poitrine. Confirmer la fermeture réussie du thorax à l&#39;aide d&#39;une petite quantité de solution saline (pas de bulles d&#39;air doivent être considérées lors de l&#39;application de pression sur la poitrine). </li><li> Regardez à travers le muscle intercostal pour confirmer expansion normale des poumons. Repositionner les deux muscles pectoraux, servantbarrière supplémentaire pour la prévention d&#39;un pneumothorax. </li></ol></li><li> Fermez la peau avec 5-0 soie sutures. </li><li> Débranchez la souris de ventilateur et permettre la récupération sur le coussin chauffant. Ne pas laisser un animal sans surveillance tant qu&#39;il a repris conscience suffisante pour maintenir décubitus sternal. Ne retournez pas un animal qui a subi une intervention chirurgicale à la compagnie d&#39;autres animaux jusqu&#39;à guérison complète. </li><li> Fournir régulièrement analgésie postopératoire (buprénorphine 0,05 mg kg SQ BID / pendant au moins 48 heures après la chirurgie). </li></ol> 2. Dans vivo mesures hémodynamiques invasive chez les souris <ol><li> Avant la procédure, immerger le 1.0 français Millar cathéter de pression dans l&#39;eau stérile à 37 ° C pendant au moins 30 min pour minimiser la dérive du signal. Étalonner le capteur électronique de pression à 0 mm Hg et 100 mm Hg et enregistrer des données à 2000 Hz. </li><li> Effectuer une anesthésie par l&#39;administration intrapéritonéale de 1,4 g / kg d&#39;uréthane. Vérifier quela souris atteint son bon plan de l&#39;anesthésie quand il ne réagit plus d&#39;un pincement de l&#39;orteil entreprise. </li><li> Placez la souris anesthésiés en position couchée. Fixer ses membres avec du ruban adhésif. Maintenir la température du corps avec un coussin chauffant et de surveiller avec une sonde rectale. Raser la région du cou et de faire une incision médiane dans la région du cou pour exposer la glande thyroïde. </li><li> Fixer le cou avec aiguilles tordues. </li><li> Tirez côté de la glande salivaire et d&#39;exposer le droit artère carotide commune. Le nerf vague, qui ressemble à un fil blanc, se trouve le long de l&#39;artère. Soigneusement séparer l&#39;artère carotide du nerf vague aide d&#39;une pince courbes. </li><li> Passez une pince courbes sous le droit artère carotide commune pour le séparer des autres tissus. Retirer le tissu conjonctif autour de l&#39;artère. </li><li> Passer deux 6-0 fils de soie sous le droit artère carotide commune. Faites un noeud serré sur le fil supérieur, qui est placé vers la tête, à proximité, et fixer avec un kocher (occlusive ligature distale). Passez la proxifils mal deux fois de gauche à droite et de fixer avec 2 kochers (fil non occlusif proximale). </li><li> Gardez l&#39;artère carotide humide en laissant tomber NaCl 0,9% stérile. Séchez excès de liquide avec des cotons-tiges. </li><li> Faire une incision dans l&#39;artère carotide droite commun avec une aiguille de calibre 26 entre la ligature distale et le fil non-occlusive proximale. </li><li> Introduire le capteur de pression dans l&#39;artère. Vérifier qu&#39;il n&#39;y a aucune perte de sang. Poussez doucement le 1,0 française Millar pression cathéter avant et réglez le câble non occlusif proximale de telle manière que le cathéter peut passer attentivement le fil sous la clavicule. <ol><li> Minimiser la perte de sang pendant le réglage du fil non-occlusive proximale. Ne pas comprimer le capteur de pression trop tout en faisant progresser car il est très fragile. Puisque le fil proximale ne doit pas obstruer l&#39;artère, le navire doit rester rempli de sang. </li></ol></li><li> Commencer à enregistrer le signal de pression. Un signal de pression artérielle Fluctuates dans une souris saine entre une pression diastolique de 60 à 70 mm Hg et une pression systolique de 100 à 120 mm Hg. </li><li> Diriger le cathéter par l&#39;artère iliaque et via l&#39;aorte dans le ventricule gauche. La pression ventriculaire oscille entre 0 mm Hg et de 100 à 120 mm Hg. Permettre au cathéter de se stabiliser à l&#39;intérieur du ventricule gauche. Enregistrer le signal de 30 min à 60 min en fonction des exigences expérimentales. </li><li> Après l&#39;achèvement de l&#39;expérience, faire tremper le cathéter dans Alconox 1% pendant 30 minutes. Laver le cathéter avec de l&#39;eau Milli-Q. Rangez le cathéter dans un bloc de mousse. </li><li> Récupérer des données à partir du logiciel d&#39;enregistrement pour une analyse ultérieure. <ol><li> Pour l&#39;analyse des données, pensez à un intervalle de temps où le signal de pression est stable. Choisissez au moins 10 cycles cardiaques consécutifs des données enregistrées d&#39;intérêt. </li><li> Utilisation LabChart version logicielle 8.0 ou similaire pour analyser la fréquence cardiaque, la pression systolique ventriculaire gauche maximale, la VentR gauche diastolique minimalepression iculier, le taux de contraction ventriculaire isovolumique gauche (dP / dt max), le taux de isovolumétrique relaxation ventriculaire gauche (dP / dt min), la pression du ventricule gauche en fin de diastole pic pic, et la constante de temps du ventriculaire isovolumique gauche la pression chute (tau) 7. NOTE: La pression de fin de diastole correspond à la pression au point de temps immédiatement avant l&#39;augmentation de la pression induite par la contraction isovolumétrique. Le calcul de la protéine tau sont basées sur le montage de la pression ventriculaire gauche dans une courbe de décroissance monoexponentielle, exprimé sous la forme P (t) = P 0 e -t / tau + b, Dans cette formule, P (t) est la pression ventriculaire gauche au moment t après que la valeur maximale négative de la dP / dt a été atteint. Le paramètre b correspond à l&#39;asymptote théorique, qui, dans une approche simplifiée peut être considérée comme nulle. Relaxation isovolumique accrue se traduit par une valeur plus faible de la protéine tau. </li></ol></li></ol&gt;

<ol>
	<li>He, 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=Risk+factors+for+congestive+heart+failure+in+US+men+and+women:+NHANES+I+epidemiologic+follow-up+study.">Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.</a> Arch Intern Med. 161, 996-1002 (2001).</li><li>Anversa, P., Sonnenblick, E. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ischemic+cardiomyopathy:+pathophysiologic+mechanisms.">Ischemic cardiomyopathy: pathophysiologic mechanisms.</a> Prog Cardiovasc Dis. 33, 49-70 (1990).</li><li>Erlebacher, J. A., Weiss, J. L., Weisfeldt, M. L., Bulkley, B. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+dilation+of+the+infarcted+segment+in+acute+transmural+myocardial+infarction:+role+of+infarct+expansion+in+acute+left+ventricular+enlargement.">Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement.</a> J Am Coll Cardiol. 4, 201-208 (1984).</li><li>Shimizu, I., 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=Excessive+cardiac+insulin+signaling+exacerbates+systolic+dysfunction+induced+by+pressure+overload+in+rodents.">Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents.</a> J Clin Invest. 120, 1506-1514 (2010).</li><li>Tirziu, D., 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+hypertrophy+in+the+absence+of+external+stimuli+is+induced+by+angiogenesis+in+mice.">Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice.</a> J Clin Invest. 117, 3188-3197 (2007).</li><li>Theilmeier, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-density+lipoproteins+and+their+constituent,+sphingosine-1-phosphate,+directly+protect+the+heart+against+ischemia/reperfusion+injury+in+vivo+via+the+S1P3+lysophospholipid+receptor.">High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor.</a> Circulation. 114, 1403-1409 (2006).</li><li>Weiss, J. L., Frederiksen, J. W., Weisfeldt, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+determinants+of+the+time-course+of+fall+in+canine+left+ventricular+pressure.">Hemodynamic determinants of the time-course of fall in canine left ventricular pressure.</a> J Clin Invest. 58, 751-760 (1976).</li><li>Bohl, S., 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=Refined+approach+for+quantification+of+in+vivo+ischemia-reperfusion+injury+in+the+mouse+heart.">Refined approach for quantification of in vivo ischemia-reperfusion injury in the mouse heart.</a> Am J Physiol Heart Circ Physiol. 297, 2054-2058 (2009).</li><li>Van Craeyveld, E., Jacobs, F., Gordts, S. C., De Geest, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-density+lipoprotein+receptor+gene+transfer+in+hypercholesterolemic+mice+improves+cardiac+function+after+myocardial+infarction.">Low-density lipoprotein receptor gene transfer in hypercholesterolemic mice improves cardiac function after myocardial infarction.</a> Gene Ther. 19, 860-871 (2012).</li><li>Gordts, S. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beneficial+effects+of+selective+HDL-raising+gene+transfer+on+survival,+cardiac+remodelling+and+cardiac+function+after+myocardial+infarction+in+mice.">Beneficial effects of selective HDL-raising gene transfer on survival, cardiac remodelling and cardiac function after myocardial infarction in mice.</a> Gene Ther. 20, 1053-1061 (2013).</li><li>Junqueira, L. C., Bignolas, G., Brentani, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Picrosirius+staining+plus+polarization+microscopy,+a+specific+method+for+collagen+detection+in+tissue+sections.">Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections.</a> Histochem J. 11, 447-455 (1979).</li><li>Patten, R. D., Hall-Porter, 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=Small+animal+models+of+heart+failure:+development+of+novel+therapies,+past+and+present.">Small animal models of heart failure: development of novel therapies, past and present.</a> Circ Heart Fail. 2, 138-144 (2009).</li><li>Zolotareva, A. G., Kogan, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+experimental+occlusive+myocardial+infarction+in+mice.">Production of experimental occlusive myocardial infarction in mice.</a> Cor Vasa. 20, 308-314 (1978).</li><li>Michael, L. H., 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+ischemia+and+reperfusion:+a+murine+model.">Myocardial ischemia and reperfusion: a murine model.</a> Am J Physiol. 269, 2147-2154 (1995).</li><li>Salto-Tellez, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Myocardial+infarction+in+the+C57BL/6J+mouse:+a+quantifiable+and+highly+reproducible+experimental+model.">Myocardial infarction in the C57BL/6J mouse: a quantifiable and highly reproducible experimental model.</a> Cardiovasc Pathol. 13, 91-97 (2004).</li><li>Fernandez, B., 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=The+coronary+arteries+of+the+C57BL/6+mouse+strains:+implications+for+comparison+with+mutant+models.">The coronary arteries of the C57BL/6 mouse strains: implications for comparison with mutant models.</a> J Anat. 212, 12-18 (2008).</li><li>Kumar, D., 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=Distinct+mouse+coronary+anatomy+and+myocardial+infarction+consequent+to+ligation.">Distinct mouse coronary anatomy and myocardial infarction consequent to ligation.</a> Coron Artery Dis. 16, 41-44 (2005).</li><li>Clauss, S. B., Walker, D. L., Kirby, M. L., Schimel, D., Lo, C. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patterning+of+coronary+arteries+in+wildtype+and+connexin43+knockout+mice.">Patterning of coronary arteries in wildtype and connexin43 knockout mice.</a> Dev Dyn. 235, 2786-2794 (2006).</li><li>Icardo, J. M., Colvee, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Origin+and+course+of+the+coronary+arteries+in+normal+mice+and+in+iv/iv+mice.">Origin and course of the coronary arteries in normal mice and in iv/iv mice.</a> J Anat. 199, 473-482 (2001).</li><li>Yoldas, A., Ozmen, E., Ozdemir, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Macroscopic+description+of+the+coronary+arteries+in+Swiss+albino+mice+(Mus+musculus).">Macroscopic description of the coronary arteries in Swiss albino mice (Mus musculus).</a> J S Afr Vet Assoc. 81, 247-252 (2010).</li><li>James, T. N., Burch, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood+supply+of+the+human+interventricular+septum.">Blood supply of the human interventricular septum.</a> Circulation. 17, 391-396 (1958).</li><li>Gao, X. M., Xu, Q., Kiriazis, H., Dart, A. M., Du, X. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+model+of+post-infarct+ventricular+rupture:+time+course,+strain-+and+gender-dependency,+tensile+strength,+and+histopathology.">Mouse model of post-infarct ventricular rupture: time course, strain- and gender-dependency, tensile strength, and histopathology.</a> Cardiovasc Res. 65, 469-477 (2005).</li><li>Muthuramu, I., Jacobs, F., Singh, N., Gordts, S. C., De Geest, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+homocysteine+lowering+gene+transfer+improves+infarct+healing,+attenuates+remodelling,+and+enhances+diastolic+function+after+myocardial+infarction+in+mice.">Selective homocysteine lowering gene transfer improves infarct healing, attenuates remodelling, and enhances diastolic function after myocardial infarction in mice.</a> PLoS One. 8, 63710 (2013).</li><li>Eaton, L. W., Weiss, J. L., Bulkley, B. H., Garrison, J. B., Weisfeldt, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regional+cardiac+dilatation+after+acute+myocardial+infarction:+recognition+by+two-dimensional+echocardiography.">Regional cardiac dilatation after acute myocardial infarction: recognition by two-dimensional echocardiography.</a> N Engl J Med. 300, 57-62 (1979).</li><li>Erlebacher, J. 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=Late+effects+of+acute+infarct+dilation+on+heart+size:+a+two+dimensional+echocardiographic+study.">Late effects of acute infarct dilation on heart size: a two dimensional echocardiographic study.</a> Am J Cardiol. 49, 1120-1126 (1982).</li><li>Schuster, E. H., Bulkley, B. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expansion+of+transmural+myocardial+infarction:+a+pathophysiologic+factor+in+cardiac+rupture.">Expansion of transmural myocardial infarction: a pathophysiologic factor in cardiac rupture.</a> Circulation. 60, 1532-1538 (1979).</li><li>Jugdutt, B. I., Michorowski, B. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+infarct+expansion+in+rupture+of+the+ventricular+septum+after+acute+myocardial+infarction:+a+two-dimensional+echocardiographic+study.">Role of infarct expansion in rupture of the ventricular septum after acute myocardial infarction: a two-dimensional echocardiographic study.</a> Clin Cardiol. 10, 641-652 (1987).</li><li>Pacher, P., Nagayama, T., Mukhopadhyay, P., Batkai, S., Kass, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+cardiac+function+using+pressure-volume+conductance+catheter+technique+in+mice+and+rats.">Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats.</a> Nat Protoc. 3, 1422-1434 (2008).</li><li>Vanden Bergh, A., Flameng, W., Herijgers, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parameters+of+ventricular+contractility+in+mice:+influence+of+load+and+sensitivity+to+changes+in+inotropic+state.">Parameters of ventricular contractility in mice: influence of load and sensitivity to changes in inotropic state.</a> Pflugers Arch. 455, 987-994 (2008).</li></ol>

None of the authors reports competing financial interests.

Changements chroniques dans la structure et la fonction du myocarde, le développement d&#39;une dysfonction ventriculaire gauche, et la progression de l&#39;insuffisance cardiaque peuvent être étudiés dans plusieurs modèles murins 12. Le remodelage cardiaque et un dysfonctionnement peut être induite par une lésion myocardique ou par la pression secondaire à une surcharge constriction aortique transverse, ou peuvent être étudiés dans des modèles génétiques de 12 cardiomyopathie dilaté...

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with the cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure1.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. In other words, ventricular remodelling concerns an alteration of the left ventricular architecture. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload (e.g., mitral insufficiency). Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure.
Loss of myocardial tissue following acute myocardial infarction results in a decreased systolic ejection and an increased left ventricular end-diastolic volume and pressure. The Frank-Starling mechanism, implying that an increased end-diastolic volume results in an increased pressure developed during systole, may help to restore cardiac output. However, the concomitant increased wall stress may induce regional hypertrophy in the non-infarcted segment, whereas in the infarcted area expansion and thinning may occur. Experimental animal studies show that the infarcted ventricle hypertrophies and that the degree of hypertrophy is dependent on the infarct size2. 
The loss of myocardial tissue following acute myocardial infarction results in a sudden increase in loading conditions. Post-infarct remodelling occurs in the setting of volume overload, since the stretched and dilated infarcted tissue increases the left ventricular volume. An increased ventricular volume not only implies increased preload (passive ventricular wall stress at the end of diastole) but also increased afterload (total myocardial wall stress during systolic ejection). Afterload is increased since the systolic radius is increased. Therefore, ventricular remodelling post-myocardial infarction is characterized by mixed features of volume overload and pressure overload.
The myocardium consists of 3 integrated components: cardiomyocytes, extracellular matrix, and the capillary microcirculation. All 3&#160;components are involved in the remodelling process. Matrix metalloproteinases produced by inflammatory cells induce degradation of intermyocyte collagen struts and cardiomyocyte slippage. This leads to infarct expansion characterized by the disproportionate thinning and dilatation of the infarct segment3. In later stages of remodelling, interstitial fibrosis is induced, which negatively affects the diastolic properties of the heart. 
The vascular and cardiomyocyte compartment in the myocardium should remain balanced in the process of ventricular remodelling to avoid tissue hypoxia4,5. Whether hypertrophy progresses to heart failure or not may be critically dependent on this balance between the vascular and cardiomyocyte compartment in the myocardium. 
A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion6. In contrast, the infarct area at 24 hours after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.

<table border="0" cellpadding="0" cellspacing="0" width="1061">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Reagents</td>
			<td style="width:223px;"></td>
			<td style="width:123px;"></td>
			<td style="width:495px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Buprenorphine (Buprenex&#174;)</td>
			<td style="width:223px;">Bedford Laboratories</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="52">
			<td height="52" style="height:52px;width:221px;">Sodium Pentobarbital (Nembutal&#174;)</td>
			<td style="width:223px;">Ceva</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="31">
			<td height="31" style="height:31px;width:221px;">Betadine&#174;</td>
			<td style="width:223px;">VWR internationals</td>
			<td>200065-400</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">5 - 0 silk suture</td>
			<td>Ethicon, Johnson &#38; Johnson Medical</td>
			<td>K890H</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">6 - 0 prolene suture&#160;</td>
			<td>Ethicon, Johnson &#38; Johnson Medical</td>
			<td>F1832</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">6 - 0 Ti- Cron suture</td>
			<td>Ethicon, Johnson &#38; Johnson Medical</td>
			<td>F1823</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Urethane&#160;</td>
			<td style="width:223px;">Sigma</td>
			<td>94300</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Alconox</td>
			<td>Alconox Inc.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;"></td>
			<td style="width:223px;"></td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Equipment</td>
			<td style="width:223px;"></td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:221px;">Ventilator, MiniVent Model 845</td>
			<td style="width:223px;">Hugo Sachs</td>
			<td style="width:123px;">73-0043</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:221px;">Chest retractor or Thorax retractor</td>
			<td style="width:223px;">Kent Scientific corporation</td>
			<td style="width:123px;">INS600240</td>
			<td>ALM Self-retaining, serrated, 7cm long, 4 x 4 &#34;L&#34; shaped prongs, 3mm x 3mm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">1.0 French Millar pressure catheter&#160;</td>
			<td style="width:223px;">Millar Instruments&#160;</td>
			<td style="width:123px;">SPR - 1000/NR</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Powerlab</td>
			<td style="width:223px;">ADInstruments Pty Ltd.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">LabChart&#174; software</td>
			<td style="width:223px;">ADInstruments Pty Ltd.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:221px;">Rectal probe</td>
			<td style="width:223px;">ADInstruments Pty Ltd.</td>
			<td style="width:123px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure

L&#39;insuffisance cardiaque est un syndrome dans lequel le cœur ne parvient pas à pomper le sang à un taux correspondant aux exigences d&#39;oxygène cellulaires au repos ou lors d&#39;un stress. Elle est caractérisée par la rétention d&#39;eau, de l&#39;essoufflement et de la fatigue, en particulier à l&#39;effort. L&#39;insuffisance cardiaque est un problème croissant de santé publique, la principale cause d&#39;hospitalisation, et une cause majeure de mortalité. La cardiopathie ischémique est la principale cause de l&#39;insuffisance cardiaque. Remodelage ventriculaire se réfère à des changements dans la structure, la taille et la forme du ventricule gauche. Ce remodelage architectural du ventricule gauche est induit par une blessure (par exemple, infarctus du myocarde), par une surcharge de pression (par exemple, hypertension artérielle systémique ou une sténose aortique), ou par une surcharge de volume. Depuis le remodelage ventriculaire affecte stress de la paroi, il a un impact profond sur la fonction cardiaque et sur le développement de l&#39;insuffisance cardiaque. Un modèle de ligature permanente de la descendin antérieure gaucheg artère coronaire chez la souris est utilisée pour étudier le remodelage ventriculaire et la fonction cardiaque post-infarctus du myocarde. Ce modèle est fondamentalement différente en termes d&#39;objectifs et la pertinence physiopathologique par rapport au modèle de ligature transitoire de l&#39;artère interventriculaire antérieure coronaire. Dans ce dernier modèle de lésion d&#39;ischémie / reperfusion, l&#39;étendue de l&#39;infarctus initial peut être modulée par des facteurs qui affectent le sauvetage myocardique suivant reperfusion. En revanche, la zone de l&#39;infarctus à 24 h après la ligature permanente de l&#39;artère interventriculaire antérieure coronaire est fixe. La fonction cardiaque dans ce modèle sera affectée par 1) le processus d&#39;expansion de l&#39;infarctus, infarctus guérison, et la formation de cicatrices; et 2) le développement concomitant de la dilatation ventriculaire gauche, hypertrophie cardiaque et le remodelage ventriculaire. Outre le modèle de ligature permanente de la descendante antérieure gauche artère coronaire, la technique de mea hémodynamique invasiveme- chez la souris est présenté en détail.

L&#39;étendue de l&#39;infarctus du myocarde peut être évaluée par Evans bleu / chlorure de 2,3,5-triphényltétrazolium (TTC) double coloration. TTC est un indicateur redox, qui est converti en 1,3,5-triphenylformazan rouge foncé dans les tissus en raison de l&#39;activité de diverses déshydrogénases, en présence de NADH vie 8. La figure 1 montre une section représentative du coeur à 24 h après ligature de l&#39;artère interventriculaire antérieure coronaire. Les zones colorée...

Watch this Scientific Journal Video about Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure at JoVE.com

Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Heart failure is the leading cause of hospitalization and a major cause of mortality. A model of permanent ligation of the left anterior descending coronary artery in mice is applied to investigate ventricular remodelling and cardiac dysfunction post-myocardial infarction. The technique of invasive hemodynamic measurements in mice is presented.

Ligature permanente de l&#39;artère interventriculaire antérieure coronaire chez la souris: Un modèle de post-infarctus du myocarde et de remodelage de l&#39;insuffisance cardiaque

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It ...

permanent-ligation-left-anterior-descending-coronary-artery-mice

Research

JoVE Journal

Medicine

27.5K vues.  Catholic University of Leuven. Heart failure is the leading cause of hospitalization and a major cause of mortality. A model of permanent ligation of the left anterior descending coronary artery in mice is applied to investigate ventricular remodelling and cardiac dysfunction post-myocardial infarction. The technique of invasive hemodynamic measurements in mice is presented.

Vidéo: Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling. 
Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy. 
Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed. 
Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical.

Numerous genetic manipulations and/or intramyocardial injections of genes, proteins, cells, and/or biomaterials are superimposed upon the dimension of time in studies of acute ischemia/ reperfusion injury and chronic remodeling in mice. This video illustrates the microsurgical procedures for ischemia/reperfusion, permanent coronary artery ligation, and intramyocardial injection studies.

Ligature de l&#39;artère coronaire et injection intramyocardique dans un modèle murin d&#39;infarctus

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo.  With the advent of genetic modifications to ...

Recherche

Médecine

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques include transient or permanent, focal or global ischemia models using many different animal models, with the most common being rodents.
The permanent MCA ligation method which is also referred as pMCAo in the literature is used extensively as a focal ischemia model in rodents 1-6. This method was originally described for rats by Tamura et al. in 1981 7. In this protocol a craniotomy was used to access the MCA and the proximal regions were occluded by electrocoagulation. The infarcts involve mostly cortical and sometimes striatal regions depending on the location of the occlusion. This technique is now well established and used in many laboratories 8-13. Early use of this technique led to the definition and description of &#x201C;infarct core&#x201D; and &#x201C;penumbra&#x201D; 14-16, and it is often used to evaluate potential neuroprotective compounds 10, 12, 13, 17. Although the initial studies were performed in rats, permanent MCA ligation has been used successfully in mice with slight modifications 18-20 .
This model yields reproducible infarcts and increased post-survival rates. Approximately 80% of the ischemic strokes in humans happen in the MCA area 21 and thus this is a very relevant model for stroke studies. Currently, there is a paucity of effective treatments available to stroke patients, and thus there is a need for good models to test potential pharmacological compounds and evaluate physiological outcomes. This method can also be used for studying intracellular hypoxia response mechanisms in vivo. 
Here, we present the MCA ligation surgery in a C57/BL6 mouse. We describe the pre-surgical preparation, MCA ligation surgery and 2,3,5 Triphenyltetrazolium chloride (TTC) staining for quantification of infarct volumes.

Middle cerebral artery (MCA) ligation is a technique to study focal cerebral ischemia in animal models. In this method, the middle cerebral artery is exposed by craniotomy and ligated by cauterization. This method gives highly reproducible infarct volumes and increased post-operative survival rates compared to other methods available.

L&#39;application de la ligature permanente artère cérébrale moyenne chez la souris

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to ...

Modified Technique for Coronary Artery Ligation in Mice

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI we need better knowledge about pathophysiology of myocardial ischemia. This knowledge may be valuable to define new therapeutic targets for innovative cardiovascular therapies4. Experimental MI model in mice is an increasingly popular small-animal model in preclinical research in which MI is induced by means of permanent or temporary ligation of left coronary artery (LCA)5. In this video, we describe the step-by-step method of how to induce experimental MI in mice.
The animal is first anesthetized with 2% isoflurane. The unconscious mouse is then intubated and connected to a ventilator for artificial ventilation. The left chest is shaved and 1.5 cm incision along mid-axillary line is made in the skin. The left pectoralis major muscle is bluntly dissociated until the ribs are exposed. The muscle layers are pulled aside and fixed with an eyelid-retractor. After these preparations, left thoracotomy is performed between the third and fourth ribs in order to visualize the anterior surface of the heart and left lung. The proximal segment of LCA artery is then ligated with a 7-0 ethilon suture which typically induces an infarct size ~40% of left ventricle. At the end, the chest is closed and the animals receive postoperative analgesia (Temgesic, 0.3 mg/50 ml, ip). The animals are kept in a warm cage until spontaneous recovery.

The surgical procedure used to induce experimental myocardial infarction in mice begins with left thoracotomy between the third and the fourth ribs in order to visualize the anterior surface of the heart and left lung. The left coronary artery is ligated, the chest is closed and the mouse is allowed to recover spontaneously.

Technique de modification de ligature de l&#39;artère coronaire chez la souris

Myocardial infarction (MI) is one of the most important causes of mortality in humans1-3. In order to improve morbidity and mortality in patients with MI ...

A Murine Model of Myocardial Ischemia-reperfusion Injury through Ligation of the Left Anterior Descending Artery

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms at work during MI and developing effective therapeutic approaches requires methodology to reproducibly simulate the clinical incidence and reflect the pathophysiological changes associated with MI. Here, we describe a surgical method to induce MI in mouse models that can be used for short-term ischemia-reperfusion (I/R) injury as well as permanent ligation. The major advantage of this method is to facilitate location of the left anterior descending artery (LAD) to allow for accurate ligation of this artery to induce ischemia in the left ventricle of the mouse heart. Accurate positioning of the ligature on the LAD increases reproducibility of infarct size and thus produces more reliable results. Greater precision in placement of the ligature will improve the standard surgical approaches to simulate MI in mice, thus reducing the number of experimental animals necessary for statistically relevant studies and improving our understanding of the mechanisms producing cardiac dysfunction following MI. This mouse model of MI is also useful for the preclinical testing of treatments targeting myocardial damage following MI.

We introduce a surgical method to induce experimental ischemia/reperfusion (I/R) injury to simulate myocardial infarction (MI) in mouse models that allows for more clarity in positioning of the ligation on the left anterior descending artery (LAD) to increase the reproducibility of MI experiments in mice.

Un modèle murin d&#39;ischémie myocardique-reperfusion par ligature de l&#39;artère interventriculaire antérieure

Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by reduced blood supply to the heart, resulting in the loss of oxygen to and the ensuing necrosis of the heart muscle. The MI model has gained popularity for its use as a short-term ischemia-reperfusion model and a long-term permanent ligation model. Below, we describe a reliable method for the permanent ligation of the LAD. With mouse genetic engineering technology becoming more advanced, and with an increasing availability of quality murine surgical instruments, the mouse has become a popular model for MI surgeries. Our surgical model incorporates the use of an easily reversible anesthetic for the rapid recovery of the mouse; a minimally invasive endotracheal intubation without involving a tracheotomy; and a thoracentesis through the original thoracotomy site without creating an additional incision in the chest, as is done in some other methods, to effectively remove excess blood and air from the chest cavity. This method is comparatively less invasive than other methods, which dramatically reduces surgical and post-surgical complications and mortality and improves reproducibility.

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

We provide a reliable method for left anterior descending artery (LAD) ligation in a mouse model. This method is comparatively less invasive than other methods, involving endotracheal intubation, a left-sided thoracotomy approach, and thoracentesis. This method can be used as a model for both acute and chronic myocardial infarction (MI).

Murine gauche interventriculaire antérieure (LAD) Coronary Artery Ligature: un modèle amélioré et simplifié pour Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ischemia and infarction in children. If left untreated, it results in a 90% mortality rate in the first year of life. In patients who survive to the adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow provide a substrate for chronic subendocardial ischemia, which may lead to left ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular arrhythmias, and sudden cardiac death. The average age of life-threatening presentation is 33 years and of sudden cardiac death 31 years. Therefore, surgical correction is highly recommended as soon as the diagnosis is made, regardless of age. In adult-type ALCAPA originating from the right-facing sinus of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is the more physiologically sound repair technique to re-establish the dual-coronary perfusion system and is recommended. This protocol describes the technique of direct re-implantation of adult-type ALCAPA into the aorta.

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

Surgical correction of ALCAPA is highly recommended, regardless of age or the degree of intercoronary collateralization. This protocol presents a technique for the direct re-implantation of adult-type ALCAPA into the aorta to re-establish the dual-coronary perfusion. Whenever feasible, direct re-implantation is preferred to other surgical correction techniques.

Re-implantation directe de gauche de l&#39;artère coronaire dans l&#39;aorte chez les adultes atteints de gauche Origine anomale coronarienne de l&#39;artère pulmonaire (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

Modèle d'infarctus myocarde de Murine utilisant la ligation permanente de l'artère coronaire descendante antérieure gauche

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...

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.

Établissement d’un modèle porcin d’insuffisance cardiaque d’infarctus post-myocardique pour le traitement des cellules souches

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major ...

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&#246;ttingen Minipigs and Landrace Pigs

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development.
Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult G&#246;ttingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model.
MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in G&#246;ttingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in G&#246;ttingen minipigs and at 2 months in Landrace pigs, respectively.
Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in G&#246;ttingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, G&#246;ttingen minipigs showed a slight increase in LVED mass only at 6 months.
In summary, this is the first characterization of post-MI HF in G&#246;ttingen minipigs in comparison to Landrace pigs, showing that the G&#246;ttingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the G&#246;ttingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in G&amp;#246;ttingen Minipigs and Landrace Pigs

The overall goal of the current study is to present the techniques of induction of myocardial infarction (MI) and post-myocardial infarction heart failure (post-MI HF) in closed-chest, adult G&#246;ttingen minipigs and the characterization of post-MI HF model in G&#246;ttingen minipigs as compared to Landrace pigs.

Insuffisance cardiaque d’infarctus post-myocardique dans le modèle d’occlusion coronaire/reperfusion à poitrine fermée chez les minipigs de Göttingen et les porcs landrace

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an ...

Generation and Characterization of Right Ventricular Myocardial Infarction Induced by Permanent Ligation of the Right Coronary Artery in Mice

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In contrast to the extensively used mouse myocardial infarction (MI) model generated by left coronary artery ligation, the RVI mouse model is rarely employed due to the difficulty associated with model generation. Research on the mechanisms and treatment of RVI-induced RV remodeling and dysfunction requires animal models to mimic the pathophysiology of RVI in patients. This study introduces a feasible procedure for RVI model generation in C57BL/6J mice. Further, this model was characterized based on the following: infarct size evaluation at 24 h after MI, assessment of cardiac remodeling and function with echocardiography, RV hemodynamics assessment, and histology of the infarct zone at 4 weeks after RVI. In addition, a coronary vasculature cast was performed to observe the coronary arterial arrangement in RV. This mouse model of RVI would facilitate the research on mechanisms of right heart failure and seek new therapeutic targets of RV remodeling.

There are several differences between the right and left ventricles. However, the pathophysiology of right ventricular infarction (RVI) has not been clarified. In the present protocol, a reproducible method for RVI mouse model generation is introduced, which may provide a means to explain the mechanism of RVI.

Génération et caractérisation de l’infarctus du myocarde ventriculaire droit induit par la ligature permanente de l’artère coronaire droite chez la souris

Right ventricular infarction (RVI) is a common presentation in clinical practice. Severe RVI can lead to fatal hemodynamic dysfunction and arrhythmia. In ...