Les auteurs tiennent à remercier les Instituts de recherche en santé (MOP53116) et l&#39;Alberta Heritage Foundation for Medical Research de la subvention de fonctionnement et fonds d&#39;établissement, respectivement, pour soutenir le développement de ce modèle expérimental.

1. Anesthésie <ol><li> Régler le débit de la machine d&#39;anesthésie à 2L/min. Connectez l&#39;échappement à aspiration sous vide. </li><li> Masque charge avec anesthésie gazeuse (isoflurane) à 5% (~ 3 minutes). </li><li> Porcelets nouveau-nés sera induite par inhalation isoflurane 5% dans l&#39;oxygène à 100% (~ 3 minutes). </li><li> Maintenir l&#39;anesthésie à 2-3% d&#39;isoflurane. Réglage fin de l&#39;isoflurane de 0,5%, selon le cas, cependant, il peut aller de 0,5 à 5% en fonction de l&#39;état de porcelets. </li><li> Une fois l&#39;accès vasculaire a été mis en place, l&#39;anesthésie par inhalation peut être activé à l&#39;anesthésie par voie intraveineuse à l&#39;aide de fentanyl (5-50 mcg / kg / h) et le midazolam (200-500 mcg / kg / h) les injections. Pancuronium (50-100 mcg / kg / h) peut être nécessaire pour contrôler les mouvements musculaires excessives au cours de la chirurgie, tandis que la capacité d&#39;observer l&#39;état des animaux est préservé pour l&#39;ajustement des médicaments anesthésiques. </li><li> Le porcelet est contrôlée par oxymétrie de pouls (percutanée d&#39;oxygène saturation à 95-100%) et de l&#39;ECG (fréquence cardiaque à 130-170 battements / min). </li><li> La température rectale du porcelet est maintenue à 38-40 ° C avec une couverture de chauffage et chauffe radiant. </li><li> L&#39;état d&#39;anesthésie des porcelets est régulièrement évaluée tout au long de la période expérimentale utilisant neurologiques (taille de la pupille, déchirent les mouvements du corps,), comportement (agitation), cardiovasculaires (tachycardie et hypertension) et respiratoire (tachypnée) les paramètres selon les besoins. Paralysie minimale est donnée. L&#39;expérience antérieure de l&#39;anesthésie des porcelets avec ou sans paralysie serait utile pour l&#39;évaluation. </li><li> Le protocole est une procédure non-survie à l&#39;euthanasie de l&#39;animal à la fin de l&#39;expérience avec une overdose de pentobarbital (100 mg / kg) par voie intraveineuse. </li></ol> 2. Mise en place chirurgicale de cathéters vasculaires à l&#39;aine (Figure 1) <ol><li> Faire un 2-3cm de long incision dans l&#39;aine droite. </li><li> Disséquer 1cm de la veine fémorale droite et 1cm right artère fémorale. Mettez deux chaînes de 3-0 autour de chaque navire. </li><li> Droit cathétérisme veineux fémoral: ligaturer la partie distale de la veine. Insérer un cathéter Argyle (3,5 ou 5 français, à double lumière) (Covidien, Mansfield, MA) à 15 cm, ce qui mettra à l&#39;oreillette droite. Lier les deux chaînes pour fixer le cathéter. Le cathéter peut être utilisé pour l&#39;entretien et le fluide de perfusion médicaments (orifice secondaire) et veineuse centrale / mesure de la pression auriculaire droite (port primaire). </li><li> Droit cathétérisme artériel fémoral: ligaturer la partie distale de l&#39;artère. Soulevez la chaîne proximale pour arrêter l&#39;écoulement du sang. Insérer un cathéter Argyle (3,5 ou 5 français, à lumière unique) à 5cm. Cela permet de placer le cathéter artériel à l&#39;aorte sous-rénale pour une mesure continue de la pression artérielle moyenne et de prélèvement de sang. Lier les deux chaînes pour fixer le cathéter. </li><li> Fermez la peau. </li></ol> 3. Mettre en place une ventilation mécanique (Figure 2) <ol><li> Faire un 2-3cm de long horizontaleincision dans le cou. </li><li> Disséquer et exposer 1cm de la trachée. Mettez deux chaînes de 1-0 autour de la trachée. </li><li> Insérez un tube endotrachéal (3,0 ou 3,5) à 1 cm dans la trachée. Connectez-vous à un ventilateur et de commencer la ventilation mécanique. Fixer la sonde endotrachéale. </li><li> Disséquer et exposer l&#39;artère carotide commune. Encerclent le navire avec une sonde à ultrasons temps de transit de flux (2SB ou 2RB, Transonic Systems Inc, Ithaque, NY) pour mesurer en continu le débit sanguin. </li></ol> 4. Placement des sondes de débit à mésentérique supérieure (figure 3) et rénale gauche (Figure 4) artères <ol><li> Doses supplémentaires de fentanyl (5-10 mcg / kg) et l&#39;acépromazine (0,01-0,02 mg / kg) sont nécessaires avant l&#39;incision. </li><li> Faire un long sous-costale-flanc incision et soigneusement disséquer les couches musculaires. </li><li> Exposer l&#39;aorte abdominale. </li><li> Minimiser la manipulation vasculaire (spasme) et les blessures lymphatique. </li><li> Disséquer 0,5-1cm artère mésentérique supérieure etmettre une sonde de débit Transonic (3SB) autour de lui. </li><li> Disséquer 0,5-1cm artère rénale gauche et mettre une sonde de débit Transonic (2SB) autour de lui. </li><li> Fermez la peau et fixez la sonde de débit. </li></ol> 5. Mise en place de la sonde cathéter dans l&#39;artère pulmonaire (figure 5) et le débit (figure 6) <ol><li> Doses supplémentaires de fentanyl (5-10 mcg / kg) et l&#39;acépromazine (0,01-0,02 mg / kg) sont nécessaires avant l&#39;incision. </li><li> Lie l&#39;animal à la position latérale droite. </li><li> Thoracotomie à l&#39;espace intercostal gauche 4e. </li><li> Méfiez-vous de l&#39;artère mammaire interne et la veine, ligaturer si nécessaire. </li><li> Utilisez un coton-tige dentaire à appuyer sur le poumon gauche et augmenter l&#39;oxygène si nécessaire. </li><li> Ouvrez le péricarde. </li><li> Identifier le canal artériel qui va de l&#39;artère pulmonaire à l&#39;aorte. </li><li> Canal artériel peut être ligaturée en plaçant un clip ou d&#39;un épais &quot;3-O soie&quot; cravate à son origine. </li><li> Libérez la principale artère pulmonaire et passe avécharpe ascular l&#39;aide d&#39;un épais &quot;0&quot; cravate. </li><li> Effectuer une chaîne porte-monnaie (5-0 prolène) de suture à la base pour la mise en place de cathéter de l&#39;artère pulmonaire. </li><li> Insérez un Angiocath 20G (avec 3 orifices latéraux moins 1 cm de l&#39;extrémité du cathéter) par l&#39;intermédiaire du cordon de bourse un maximum de 1 cm. </li><li> Vérifiez la libre circulation du sang veineux. </li><li> Connectez-vous à transducteur de pression, vérifier la pression artérielle pulmonaire et de forme d&#39;onde. </li><li> Serrer la chaîne de sac à main et fixer le cathéter pulmonaire. </li><li> Placer une sonde de débit Transonic (6SB) autour de l&#39;artère pulmonaire. </li><li> Placez gel ultrasonore entre la sonde de débit et de l&#39;artère afin de permettre la transduction du signal optimale. </li><li> Recouvrez la plaie avec de la gaze humide saline. </li></ol> 6. L&#39;hypoxie réoxygénation et le protocole <ol><li> Diminuer la concentration d&#39;oxygène inspiré à 10%, en augmentant la concentration de l&#39;azote gazeux inhalé pour induire une hypoxémie. </li><li> Réglez l&#39;oxygène inspiréconcentration comprise entre 10% et 15% pour obtenir une PaO 2 de 20-40 mmHg ou SaO 2 de 30-40% pendant 2 heures. </li><li> Effectuer des analyses de sang artériel pour évaluer la PaCO 2 et régler le taux ventilateur en conséquence. </li><li> Avec l&#39;induction de l&#39;hypoxie, la première heure est consacrée à l&#39;induction d&#39;une tachycardie régulière (et le débit cardiaque) réponse. </li><li> Continuer à surveiller les changements dans la circulation sanguine à la carotide commune, mésentérique supérieure et gauche artères rénales. </li><li> Au cours de la deuxième heure de l&#39;hypoxie, le stress hypoxique est porté à la sortie constamment inférieure cardiaque à 30-40% du niveau de référence, la pression artérielle moyenne à 30-35 mmHg et un pH artériel 6,95 à 7,05. </li><li> Stress hypoxique peut être mis fin prématurément ou prolongée de 15 minutes, selon le cas. </li><li> Augmenter la concentration d&#39;oxygène inspiré brusquement à 100% en cessant brusquement de l&#39;azote gazeux, tout en continuant d&#39;oxygène pur. </li><li> Surveiller le débit cardiaque, la pression artérielle moyenne et hémodynamique par d&#39;autresmètres pour une récupération rapide. </li><li> Réanimation avec 100% d&#39;oxygène peut être poursuivi pendant 0,5 heure. Après cette période de temps, de réduire la concentration d&#39;oxygène inspiré rapidement à 21%. </li><li> Continuer réoxygénation avec 21% d&#39;oxygène pour la période restante de l&#39;expérience. La concentration d&#39;oxygène inspiré peut être augmentée à 25% si nécessaire. </li><li> Bolus de liquide de 10 ml solution de lactate / kg de Ringer peut être nécessaire, le cas échéant au cours de la période expérimentale. Son utilisation doit être protocolized. </li></ol> 7. Les résultats représentatifs: L&#39;induction de l&#39;hypoxémie chez le porcelet nouveau-né au cours de la première heure de l&#39;hypoxie devrait augmenter le débit cardiaque (débit artériel pulmonaire) à 120% -130% du niveau de référence (figure 7A) et la fréquence cardiaque (figure 7B). Typiquement, le débit cardiaque devrait atteindre son pic de rémunération entre la première et 0,5 h 1h de l&#39;hypoxie. En outre, le flux sanguin devrait être centralisée résultant en moi a diminuéperfusion rénale et senteric mais une nature préservée ou augmentée ordinaires accréditives carotide (figure 8). Au cours de la deuxième heure de l&#39;hypoxie, il ya une diminution constante du débit cardiaque, de l&#39;hypotension développement (Figure 9A), ralentissement du rythme cardiaque, avec ou sans arythmie s&#39;est produite. L&#39;hypoxie devrait induire une hypertension artérielle pulmonaire avec augmentation de la pression artérielle pulmonaire (Figure 9B), ce qui peut parfois réduire dans la finale de 30 min d &#39;hypoxie que les diminutions du débit cardiaque. Après la réanimation, tous les paramètres hémodynamiques sera immédiatement rétabli à la valeur initiale normoxique, à l&#39;exception du débit sanguin rénal, qui récupère peu à peu au cours de la première heure de réoxygénation. Toutefois, les paramètres hémodynamiques en particulier pour le débit cardiaque et la pression artérielle moyenne va progressivement se détériorer au cours des 2 premières heures de la réoxygénation à environ 70-75% du niveau de référence normoxique et 35-45 mmHg, respectivement. Cette cardiovasculaires dysfunctisur au moins en partie, pour la sidération myocardique et garantit cardiovasculaires thérapies de soutien tels que vasoactif et agents inotropes. <img alt="Figure 1" src="/files/ftp_upload/3166/3166fig1.jpg" /> Figure 1: incision inguinale avec la mise en place de cathéters fémoraux artériels et veineux <img alt="Figure 2" src="/files/ftp_upload/3166/3166fig2.jpg" /> Figure 2: incision du cou avec la mise en place d&#39;une sonde endotrachéale et une sonde de flux autour de l&#39;artère carotide commune <img alt="Figure 3" src="/files/ftp_upload/3166/3166fig3.jpg" /> Figure 3: incision du flanc de l&#39;isolement de l&#39;artère mésentérique supérieure <img alt="Figure 4" src="/files/ftp_upload/3166/3166fig4.jpg" /> Figure 4: incision du flanc avec l&#39;isolement de l&#39;artère rénale gauche <img alt="Figure 5" src = &quot;/ files/ftp_upload/3166/3166fig5.jpg&quot; /&gt; Figure 5: thoracotomie avec la mise en place d&#39;un cathéter artériel pulmonaire <img alt="Figure 6" src="/files/ftp_upload/3166/3166fig6.jpg" /> Figure 6: thoracotomie avec la mise en place d&#39;une sonde de flux transsonique autour artère pulmonaire principale <img alt="Figure 7" src="/files/ftp_upload/3166/3166fig7.jpg" /> Figure 7: Changements dans le temps (A) du débit cardiaque (débit artériel pulmonaire) et la fréquence cardiaque (B) au cours de l&#39;hypoxie réoxygénation et <img alt="Figure 8" src="/files/ftp_upload/3166/3166fig8.jpg" /> Figure 8: Changements temporels dans la circulation sanguine à (A) carotide commune, (B) et mésentériques supérieure (C) gauche artères rénales au cours de l&#39;hypoxie réoxygénation et <img alt="Figure 9" src="/files/ftp_upload/3166/3166fig9.jpg" /> Figure 9: Temporalvariation de (A) la pression artérielle moyenne et (B) la pression artérielle pulmonaire au cours de l&#39;hypoxie réoxygénation et

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Le protocole expérimental actuel a l&#39;avantage d&#39;examiner les changements systémiques et régionales hémodynamiques chez les sujets nouveau-nés pendant le processus de l&#39;hypoxie et de la réoxygénation. Nous pouvons aussi examiner l&#39;effet respectif des interventions visant à améliorer la fonction cardio-vasculaire lors de la récupération. Nous et d&#39;autres ont rapporté l&#39;expérience et les résultats de l&#39;étude de l&#39;asphyxie néonatale concernant les effets cardiovasculaires à <...

a swine model of neonatal asphyxia

Chaque année, plus de 1 million de nouveau-nés meurent dans le monde entier comme liée à l&#39;asphyxie. Nouveau-nés asphyxiés ont généralement une défaillance multiviscérale, y compris déficit de perfusion hypotension,, encéphalopathie hypoxique-ischémique, l&#39;hypertension pulmonaire, entérocolite vasculopathic, l&#39;insuffisance rénale et de complications thrombo-emboliques. Les modèles animaux sont mis au point pour nous aider à comprendre la physiopathologie et de la pharmacologie de l&#39;asphyxie néonatale. En comparaison avec les rongeurs et les agneaux nouveau-nés, le porcelet nouveau-né a été prouvé d&#39;être un modèle utile. Le porcelet nouveau-né présente plusieurs avantages, notamment le développement similaire à celle de 36-38 semaines de grossesse le fœtus humain avec les systèmes du corps comparables, la taille du corps de grande taille (~ 1,5 à 2 kg à la naissance), qui permet l&#39;instrumentation et le contrôle de l&#39;animal et de contrôler les variables confondantes de dérangements hypoxie et hémodynamiques. Nous décrivons ici un protocole expérimental pour simuler l&#39;asphyxie néonatale et nous permettent d&#39;examiner la systématisationmicro et régionales changements hémodynamiques au cours du processus asphyxiant et réoxygénation ainsi que les effets respectifs des interventions. En outre, le modèle a l&#39;avantage d&#39;étudier une défaillance multiviscérale ou un dysfonctionnement simultanément et l&#39;interaction avec les différents systèmes du corps. Le modèle expérimental est une procédure non-survie qui implique l&#39;instrumentation chirurgicale des porcelets nouveau-nés (1-3 day-old et 1,5-2,5 kg de poids, race mixte) afin de permettre la mise en place de la ventilation mécanique, vasculaire (artériel et veineux central) accès et la mise en place de cathéters et les sondes d&#39;écoulement transsonique (rl) pour la surveillance en continu de la pression intra-vasculaire et la circulation sanguine dans différentes artères pulmonaires incluant principal, la carotide commune, mésentérique supérieure et gauche artères rénales. L&#39;utilisation de ces porcelets chirurgicalement instrumentés, après stabilisation pendant 30-60 minutes tels que définis par la variation de Z &lt;10% dans les paramètres hémodynamiques et les gaz sanguins normaux, nous commençons un protocole expérimentald&#39;hypoxémie sévère qui est induite par l&#39;hypoxie alvéolaire normocapnic. Le porcelet est ventilé avec de l&#39;oxygène à 10-15% en augmentant la concentration d&#39;azote inhalé pendant 2h, dans le but de saturation en oxygène artériel de 30-40%. Ce degré d&#39;hypoxémie va produire l&#39;asphyxie clinique avec une acidose métabolique sévère, hypotension systémique et choc cardiogénique avec une hypoperfusion des organes vitaux. L&#39;hypoxie est suivie d&#39;une réoxygénation de l&#39;oxygène à 100% pendant 0,5 heure, puis 21% d&#39;oxygène pour 3.5h. Les interventions pharmacologiques peuvent être introduits en temps voulu et de leurs effets étudiés en aveugle, randomisée bloc-mode.

Watch this Scientific Journal Video about A Swine Model of Neonatal Asphyxia at JoVE.com

A Swine Model of Neonatal Asphyxia

Modèles animaux de grande taille ont de bonnes valeurs de translation dans l&#39;examen de la physiologie et de la pharmacologie de l&#39;asphyxie néonatale. Utilisation porcelets nouveau-nés, nous développons un protocole expérimental pour simuler l&#39;asphyxie néonatale, qui a des avantages de l&#39;étude des paramètres hémodynamiques systémiques et régionales, transport de l&#39;oxygène aux voies biochimiques et pathologiques et des corrélations.

Un modèle porcin de l&#39;asphyxie néonatale

Annually more than 1 million neonates die worldwide as related to asphyxia. Asphyxiated neonates commonly have multi-organ failure including hypotension, ...

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14.2K vues.  University of Alberta. Modèles animaux de grande taille ont de bonnes valeurs de translation dans l'examen de la physiologie et de la pharmacologie de l'asphyxie néonatale. Utilisation porcelets nouveau-nés, nous développons un protocole expérimental pour simuler l'asphyxie néonatale, qui a des avantages de l'étude des paramètres hémodynamiques systémiques et régionales, transport de l'oxygène aux voies biochimiques et pathologiques et des corrélations.

Vidéo: A Swine Model of Neonatal Asphyxia

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world&#8217;s 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials1,2. The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (&#60; 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

Hypoxic-ischemic encephalopathy following perinatal asphyxia can be studied using animal models. We demonstrate the procedures necessary for establishing a piglet model of neonatal hypoxic-ischemic encephalopathy.

Un modèle de Porcinet néonatale encéphalopathie hypoxique-ischémique

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the ...

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Médecine

A Neonatal Mouse Spinal Cord Compression Injury Model

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal cord. A major current area of research is focused on the mechanisms of adaptive plasticity that underlie spontaneous or induced functional recovery following SCI. Spontaneous functional recovery is reported to be greater early in life, raising interesting questions about how adaptive plasticity changes as the spinal cord develops. To facilitate investigation of this dynamic, we have developed a SCI model in the neonatal mouse. The model has relevance for pediatric SCI, which is too little studied. Because neural plasticity in the adult involves some of the same mechanisms as neural plasticity in early life1, this model may potentially have some relevance also for adult SCI. Here we describe the entire procedure for generating a reproducible spinal cord compression (SCC) injury in the neonatal mouse as early as postnatal (P) day 1. SCC is achieved by performing a laminectomy at a given spinal level (here described at thoracic levels 9-11) and then using a modified Yasargil aneurysm mini-clip to rapidly compress and decompress the spinal cord. As previously described, the injured neonatal mice can be tested for behavioral deficits or sacrificed for ex vivo physiological analysis of synaptic connectivity using electrophysiological and high-throughput optical recording techniques1. Earlier and ongoing studies using behavioral and physiological assessment have demonstrated a dramatic, acute impairment of hindlimb motility followed by a complete functional recovery within 2 weeks, and the first evidence of changes in functional circuitry at the level of identified descending synaptic connections1.

This article describes a method for generating a reproducible spinal cord compression injury (SCI) in the neonatal mouse. The model provides an advantageous platform for studying mechanisms of adaptive plasticity that underlie spontaneous functional recovery.

Un nouveau-né de la moelle épinière de souris Compression Modèle de lésion

Spinal cord injury (SCI) typically causes devastating neurological deficits, particularly through damage to fibers descending from the brain to the spinal ...

Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by isoflurane and placed on an ice pad to induce hypothermia. After the chest is opened, and the left anterior descending coronary artery (LAD) is visualized, a suture is placed around the LAD to inflict myocardial ischemia in the left ventricle. The surgical procedure takes 10-15 min. Visualizing the coronary artery is crucial for accurate suture placement and reproducibility. Myocardial infarction and cardiac dysfunction are confirmed by triphenyl-tetrazolium chloride (TTC) staining and echocardiography, respectively. Complete regeneration 21 days post myocardial infarction is verified by histology. This protocol can be used to as a tool to elucidate mechanisms of mammalian cardiac regeneration after myocardial infarction.

This protocol describes a highly reproducible model of cardiac regeneration by surgical induction of myocardial infarction in the left ventricle of postnatal day 1 mice. The method involves induction of hypothermic anesthesia and ligation of the left anterior descending coronary artery.

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

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and ...

A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor

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

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

Un modèle d’ischémie cardiaque chronique chez les porcs à l’aide d’un Constrictor Améroïde

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

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine.
A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. 
After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing.
This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.

Here, we present a protocol to produce tachycardia-induced cardiomyopathy in swine. This model represents a potent way to study the hemodynamics of progressive chronic heart failure and the effects of applied treatment.

Cardiomyopathie induite par la tachycardie comme un modèle de l’insuffisance cardiaque chronique chez le porc

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment ...

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological pathways impair the inflammation response, resulting in delayed wound healing. Impaired wound healing frequently occurs in patients with diabetes leading to unfavorable outcomes such as amputation. Hence, dressings having beneficial effect in promoting burn wound repair are needed. However, studies on burn wound treatment are limited due to lack of proper animal models. Our previous study demonstrated wound-healing performance in rat and swine models using a minimally invasive surgical technique. This study aimed to demonstrate a swine model of severe burn injury that eliminates wound contraction and more closely approximates the human processes of re-epithelialization and new tissue formation. This protocol provides a detailed procedure for creating consistent burn wounds and examining the wound-healing performance under the treatment of an experimental dressing in a swine model. Six burn wounds were created symmetrically on the dorsum, which were covered with a clinical dressing composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. Upon the completion of experiments, wound closure, wound area, and Vancouver Scar Scale score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin staining. Antibacterial activity of each dressing in the context of wound healing was also examined. The application of the clinical dressing to the wounds in swine model mimics the biological processes of human wound healing with respect to the processes of epithelialization, cellular proliferation, and angiogenesis. Therefore, this swine model provides an easy-to-learn, cost-effective, and robust method to assess the effect of clinical dressings in severe burn injury.

To closely mimic the mode of burn injuries requires the interplay between clinical observation and studies in animal models. In this study, a swine model of severe burn injury was established to assess an experimental dressing in physiological and pathophysiological settings.

Brûlures graves dans un modèle de porcs pour évaluation clinique vinaigrette

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

Mesure de la contractilité isométrique de l’artère mésentérique de souris à l’aide de fil myographie

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

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 ...

Myocardial Infarction by Percutaneous Embolization Coil Deployment in a Swine Model

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization and cardiovascular drugs, a significant proportion of patients develop pathological left-ventricular remodeling and progressive heart failure following MI. Therefore, new therapeutic options, such as cellular and gene therapies, among others, have been developed to repair and regenerate injured myocardium. In this context, animal models of MI are crucial in exploring the safety and efficacy of these experimental therapies before clinical translation. Large animal models such as swine are preferred over smaller ones due to the high similarity of swine and human hearts in terms of coronary artery anatomy, cardiac kinetics, and the post-MI healing process. Here, we aimed to describe an MI model in pig by permanent coil deployment. Briefly, it comprises a percutaneous selective coronary artery cannulation through retrograde femoral access. Following coronary angiography, the coil is deployed at the target branch under fluoroscopic guidance. Finally, complete occlusion is confirmed by repeated coronary angiography. This approach is feasible, highly reproducible, and emulates the pathogenesis of human non-revascularized MI, avoiding the traditional open-chest surgery and the subsequent postoperative inflammation. Depending on the time of follow-up, the technique is suitable for acute, sub-acute, or chronic MI models.

Myocardial infarction (MI) animal models that emulate the natural process of the disease in humans are crucial to understanding pathophysiological mechanisms and testing the safety and efficacy of new emergent therapies. Here, we describe an MI swine model created by deploying a percutaneous embolization coil.

Infarctus du myocarde par déploiement de bobine d’embolisation percutanée dans un modèle porcin

Myocardial infarction (MI) is the leading cause of mortality worldwide. Despite the use of evidence-based treatments, including coronary revascularization ...

A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight infants, with high mortality and unclear pathogenesis. The cause of NEC may be related to inflammatory immune regulatory system abnormalities. An NEC animal model is an indispensable tool for NEC disease immune research. NEC animal models usually use C57BL/6J neonatal mice; BALB/c neonatal mice are rarely used. Related studies have shown that when mice are infected, Th2 cell differentiation is predominant in BALB/c mice compared to C57BL/6J mice. Studies have suggested that the occurrence and development of NEC are associated with an increase in T helper type 2 (Th2) cells and are generally accompanied by infection. Therefore, this study used neonatal BALB/c mice to induce an NEC model with similar clinical characteristics and intestinal pathological changes as those observed in children with NEC. Further study is warranted to determine whether this animal model could be used to study Th2 cell responses in NEC.

Un modèle murin BALB/c néonatal d’entérocolite nécrosante

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight ...