Gli autori desiderano ringraziare il Canadian Institutes of Health Research (MOP53116) e Alberta Heritage Foundation for Medical Research per la sovvenzione di funzionamento e del fondo stabilimento, rispettivamente, per sostenere lo sviluppo di questo modello sperimentale.

1. Anestesia <ol><li> Impostare la portata della macchina anestetica a 2l/min. Collegare lo scarico di aspirazione di vuoto. </li><li> Carica maschera viso con gas anestetico (isoflurano) al 5% (~ 3 min). </li><li> Suinetti appena nati saranno indotti per via inalatoria con isoflurano 5% in ossigeno al 100% (~ 3 min). </li><li> Mantenere l&#39;anestesia al 2-3% del isoflurano. Regolazione fine Isoflurane da 0,5% a seconda dei casi, tuttavia, può variare da 0,5 a 5% a seconda delle condizioni di maialini. </li><li> Una volta che l&#39;accesso vascolare è stata stabilita, l&#39;anestesia inalatoria può essere commutato anestesia endovenosa con fentanyl (5-50 mcg / kg / h) e midazolam (200-500 mcg / kg / h) infusioni. Pancuronium (50-100 mcg / kg / h), può essere richiesto di controllare i movimenti eccessivi durante l&#39;intervento chirurgico, mentre la capacità di osservare lo stato dell&#39;animale è conservato per la registrazione dei farmaci anestetici. </li><li> Il maialino è monitorato da pulsossimetria (percutanea di ossigeno saturation al 95-100%) e l&#39;ECG (frequenza cardiaca a 130-170 battiti / min). </li><li> Temperatura rettale Il maialino è mantenuta a 38-40 ° C con coperta termica e più caldo radiante. </li><li> Lo stato anestetico di maialino viene regolarmente valutata per tutto il periodo sperimentale utilizzando neurologici (diametro pupillare, lacrimazione, movimenti del corpo), comportamentali (agitazione), cardiovascolare (tachicardia e ipertensione) e respiratorio (tachipnea) i parametri a seconda dei casi. Paralisi minima è dato. Precedenti esperienze di anestesia per i suinetti con e senza paralisi sarebbe utile per la valutazione. </li><li> Il protocollo è un non-sopravvivenza procedura con euthanization dell&#39;animale alla fine dell&#39;esperimento con una overdose di pentobarbital (100 mg / kg) per via endovenosa. </li></ol> 2. Posizionamento chirurgico di cateteri vascolari all&#39;inguine (Figura 1) <ol><li> Fai un lungo 2-3cm incisione a livello inguinale destra. </li><li> Dissect 1 cm di venoso femorale destra e 1cm right arteria femorale. Metti due 3-0 stringhe attorno ad ogni nave. </li><li> Diritto cateterismo venoso femorale: Legare il distale della vena. Inserire un catetere Argyle (3.5 o 5 francese, a doppio lume) (Covidien, Mansfield, MA) a 15 cm e questo luogo presso l&#39;atrio destro. Tie entrambe le stringhe per fissare il catetere. Il catetere può essere utilizzato per la manutenzione e fluido di infusione di farmaci (porta secondaria) e venosa centrale / destra misurazione della pressione atriale (porta primaria). </li><li> Diritto cateterismo arterioso femorale: Legare il distale dell&#39;arteria. Sollevare la stringa prossimale per arrestare il flusso di sangue. Inserire un catetere Argyle (3.5 o 5 Francese, a lume singolo) a 5cm. Questo metterà il catetere arterioso alla infra-renale dell&#39;aorta per la misura continua della pressione arteriosa media e prelievo di sangue. Tie entrambe le stringhe per fissare il catetere. </li><li> Chiudere la pelle. </li></ol> 3. Stabilire ventilazione meccanica (Figura 2) <ol><li> Fai un lungo 2-3cm orizzontaleincisione nel collo. </li><li> Staccare ed esporre 1 cm di trachea. Mettere due stringhe 1-0 intorno alla trachea. </li><li> Inserire un tubo endotracheale (3.0 o 3.5) a 1 centimetro in trachea. Connettersi a un ventilatore e iniziare la ventilazione meccanica. Fissare il tubo endotracheale. </li><li> Sezionare ed esporre la carotide comune. Restringere la nave con una sonda ad ultrasuoni flusso del tempo di transito (o 2SB 2RB, Transonic Systems Inc., Ithica, NY) per misurare in continuo il flusso di sangue. </li></ol> 4. Posizionamento di sonde di flusso alla mesenterica superiore (Figura 3) e renale sinistra (Figura 4) arterie <ol><li> Dosi di fentanil (5-10 mcg / kg) e acepromazina (0,01-0,02 mg / kg) sono necessari prima della incisione cutanea. </li><li> Fai un lungo sottocostale fianco di incisione e con attenzione sezionare strati muscolari. </li><li> Esporre l&#39;aorta addominale. </li><li> Ridurre al minimo la manipolazione vascolare (vasospasmo) e lesioni linfatico. </li><li> Dissect 0,5-1cm arteria mesenterica superiore emettere una sonda di flusso Transonic (3SB) intorno ad esso. </li><li> Dissect 0,5-1cm arteria renale sinistra e mettere una sonda di flusso Transonic (2SB) intorno ad esso. </li><li> Chiudere la pelle e fissare la sonda di flusso. </li></ol> 5. Posizionamento del catetere arterioso polmonare (Figura 5) e portata della sonda (Figura 6) <ol><li> Dosi di fentanil (5-10 mcg / kg) e acepromazina (0,01-0,02 mg / kg) sono necessari prima della incisione cutanea. </li><li> Lie l&#39;animale nella posizione di laterale destro. </li><li> Toracotomia sinistra al 4 ° spazio intercostale. </li><li> Attenzione per l&#39;arteria mammaria interna e la vena, legare se necessario. </li><li> Usare un tampone dentale per premere il polmone sinistro e aumentare l&#39;ossigeno, se necessario. </li><li> Aprire il pericardio. </li><li> Identificare il dotto arterioso che va da l&#39;arteria polmonare all&#39;aorta. </li><li> Dotto arterioso può essere legato mettendo una clip o da una spessa &quot;3-O di seta&quot; legame alla sua origine. </li><li> Libera la principale arteria polmonare e passaggio avfionda ascular usando una spessa cravatta &quot;0&quot;. </li><li> Eseguire una stringa borsa (5-0 prolene) sutura alla base per l&#39;inserimento di catetere in arteria polmonare. </li><li> Inserire un catetere venoso 20G (con tre fori laterali inferiori a 1 cm dalla punta del catetere) attraverso la stringa borsa per un massimo di 1 cm. </li><li> Verificare la presenza di libero flusso di sangue venoso. </li><li> Connettersi a trasduttore di pressione, verificare la presenza di pressione arteriosa polmonare e la forma d&#39;onda. </li><li> Stringere la stringa borsa e fissare il catetere polmonare. </li><li> Posizionare una sonda Transonic flusso (6SB) attorno alla principale arteria polmonare. </li><li> Inserire gel per ultrasuoni tra la sonda di flusso e l&#39;arteria per consentire trasduzione del segnale ottimale. </li><li> Coprire la ferita con garza umida soluzione fisiologica. </li></ol> 6. L&#39;ipossia e riossigenazione protocollo <ol><li> Diminuire la concentrazione inspirata di ossigeno al 10% aumentando la concentrazione di gas azoto inalato per indurre ipossiemia. </li><li> Regolare l&#39;ossigeno inspiratoconcentrazione tra il 10% e il 15% per ottenere una PaO2 di 20-40 mmHg o SaO2 del 30-40% per 2h. </li><li> Eseguire l&#39;analisi del sangue arterioso per valutare PaCO2 e regolare la velocità del ventilatore di conseguenza. </li><li> Con l&#39;induzione di ipossiemia, la prima ora è dedicata costantemente indurre una tachicardia (e della gittata cardiaca) risposta. </li><li> Continuare a monitorare i cambiamenti del flusso sanguigno alla carotide comune, mesenterica superiore e sinistra arterie renali. </li><li> Durante la seconda ora di ipossia, lo stress ipossico è aumentato a uscita costantemente inferiore cardiaca al 30-40% della linea di base, la pressione arteriosa media a 30-35 mmHg e pH arterioso 6,95-7,05. </li><li> Stress ipossico può essere terminato prematuramente o prorogato di 15 min a seconda dei casi. </li><li> Aumenta la concentrazione di ossigeno inspirato bruscamente al 100% interrompendo bruscamente gas di azoto, pur continuando ossigeno puro. </li><li> Monitorare la gittata cardiaca, la pressione arteriosa media e di altri emodinamica parametri per un rapido recupero. </li><li> Rianimazione con il 100% di ossigeno può essere continuato per 0.5h. Dopo questo periodo di tempo, di ridurre la concentrazione di ossigeno inspirato rapidamente al 21%. </li><li> Continuare riossigenazione con il 21% di ossigeno per il restante periodo di esperimento. La concentrazione di ossigeno inspirato può essere titolato al 25%, se necessario. </li><li> Boli Fluid da 10 ml di soluzione di lattato / kg di Ringer può essere necessario a seconda dei casi durante il periodo di sperimentazione. Il suo uso deve essere protocolized. </li></ol> 7. Rappresentante dei risultati: L&#39;induzione di ipossiemia nel suinetto neonato sulla prima ora di ipossia dovrebbe aumentare la portata cardiaca (flusso arterioso polmonare) al 120% -130% del valore basale (Figura 7A) e frequenza cardiaca (Figura 7B). In genere, la gittata cardiaca raggiunge il suo picco di compensazione tra il primo e il 1h 0.5h di ipossia. Inoltre, il flusso di sangue dovrebbe diventare centralizzata con conseguente diminuzione meperfusione senteric e renale, ma una preservata comune o un aumento del flusso arterioso carotideo (Figura 8). Durante la seconda ora di ipossia, vi è una costante diminuzione della gittata cardiaca, di ipotensione (Figura 9A), rallentamento della frequenza cardiaca con o senza aritmia verificato. L&#39;ipossia dovrebbe indurre ipertensione polmonare con un aumento della pressione arteriosa polmonare (Figura 9B), che talvolta può abbassare in finale 30 minuti di ipossia al diminuire della gittata cardiaca. Su rianimazione, tutti i parametri emodinamici si recupera immediatamente al basale normossica, tranne per il flusso sanguigno renale che recupera gradualmente la prima ora di riossigenazione. Tuttavia, i parametri emodinamici soprattutto per la gittata cardiaca e la pressione arteriosa media peggiorerà gradualmente il primo 2 ore della riossigenazione a circa il 70-75% del basale normossia e 35-45 mmHg, rispettivamente. Questo cardiovascolare dysfunction è almeno in parte per miocardio terapie cardiovascolari mozzafiato e garantisce di supporto quali vasoattivo e agenti inotropi. <img alt="Figura 1" src="/files/ftp_upload/3166/3166fig1.jpg" /> Figura 1: incisione inguinale con il posizionamento di cateteri femorali arteriose e venose <img alt="Figura 2" src="/files/ftp_upload/3166/3166fig2.jpg" /> Figura 2: incisione del collo con il posizionamento di un tubo endotracheale e una sonda di flusso intorno alla carotide comune <img alt="Figura 3" src="/files/ftp_upload/3166/3166fig3.jpg" /> Figura 3: incisione Fianco con l&#39;isolamento dell&#39;arteria mesenterica superiore <img alt="Figura 4" src="/files/ftp_upload/3166/3166fig4.jpg" /> Figura 4: incisione Fianco con l&#39;isolamento di sinistra dell&#39;arteria renale <img alt="Figura 5" src = &quot;/ files/ftp_upload/3166/3166fig5.jpg&quot; /&gt; Figura 5: toracotomia con il posizionamento del catetere in arteria polmonare <img alt="Figura 6" src="/files/ftp_upload/3166/3166fig6.jpg" /> Figura 6: toracotomia con l&#39;inserimento di una sonda di flusso Transonic intorno principale arteria polmonare <img alt="Figura 7" src="/files/ftp_upload/3166/3166fig7.jpg" /> Figura 7: variazioni temporali in (A), la gittata cardiaca (flusso arterioso polmonare) e (B) la frequenza cardiaca durante l&#39;ipossia e riossigenazione <img alt="Figura 8" src="/files/ftp_upload/3166/3166fig8.jpg" /> Figura 8: variazioni temporali del flusso sanguigno a (A) carotide comune, (B) e mesenterica superiore (C) delle arterie renali sinistra durante ipossia e riossigenazione <img alt="Figura 9" src="/files/ftp_upload/3166/3166fig9.jpg" /> Figura 9: temporalevariazioni (A) pressione arteriosa media e (B) la pressione arteriosa polmonare durante l&#39;ipossia e riossigenazione

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L&#39;attuale protocollo sperimentale ha un vantaggio per esaminare i cambiamenti sistemici e regionali emodinamici nei soggetti neonatale durante il processo di ipossia e riossigenazione. Possiamo anche esaminare l&#39;effetto relativo di interventi utilizzati per migliorare la funzione cardiovascolare durante il recupero. Noi e altri hanno riportato l&#39;esperienza e risultati nello studio di asfissia neonatale quanto riguarda gli effetti cardiovascolari in 1, polmonare 2, neurologica 3,</s...

a swine model of neonatal asphyxia

Ogni anno più di 1 milione di neonati muoiono in tutto il mondo in relazione alla asfissia. Neonati asfittici hanno comunemente insufficienza multi-organo tra cui ipotensione, deficit di perfusione, encefalopatia ipossico-ischemica, ipertensione polmonare, enterocolite alterazioni vasculopatiche, insufficienza renale e complicazioni tromboemboliche. I modelli animali sono stati sviluppati per aiutarci a capire la fisiopatologia e la farmacologia di asfissia neonatale. In confronto a roditori e gli agnelli appena nato, il maialino appena nato ha dimostrato di essere un modello valido. Il maialino neonato ha diversi vantaggi tra cui lo sviluppo simile a quello di 36-38 settimane feto umano di sistemi a casse comparabili, dimensione del corpo di grandi dimensioni (~ 1,5-2 kg alla nascita), che permette la strumentazione e il controllo degli animali e controlla le variabili confondenti di ipossia e alterazioni emodinamiche. Noi qui descrivono un protocollo sperimentale per simulare asfissia neonatale e ci permettono di esaminare la systemicrofono e regionali modificazioni emodinamiche durante il processo asfissiante e riossigenazione nonché i rispettivi effetti di interventi. Inoltre, il modello ha il vantaggio di studiare multi-organo o disfunzione simultaneamente e l&#39;interazione con i diversi sistemi dell&#39;organismo. Il modello sperimentale è un non-sopravvivenza procedura che comporta la strumentazione chirurgica dei suinetti neonati (1-3 pulcini di un giorno e di 1,5-2,5 kg di peso, razza mista) per consentire la creazione di ventilazione meccanica, vascolare (arterioso e venoso centrale) a e il posizionamento di cateteri e sonde di flusso Transonic (Inc.) per il monitoraggio continuo della pressione intra-vascolare e del flusso sanguigno attraverso le arterie differenti compreso polmonare principale, carotide comune, mesenterica superiore e sinistro arterie renali. L&#39;utilizzo di questi chirurgicamente suinetti strumentati, dopo la stabilizzazione per 30-60 minuti, come definiti dalla variazione Z &lt;10% dei parametri emodinamici ed emogasanalisi normali, abbiamo varato un protocollo sperimentaledi grave ipossiemia che è indotto tramite normocapnic ipossia alveolare. Il maialino è ventilato con 10-15% di ossigeno aumentando la concentrazione di gas azoto inalato per 2h, mirando saturazione arteriosa di ossigeno del 30-40%. Questo grado di ipossiemia produrrà asfissia clinica con grave acidosi metabolica, ipotensione sistemica e shock cardiogeno con ipoperfusione agli organi vitali. L&#39;ipossia è seguita da riossigenazione con il 100% di ossigeno per 0.5h e quindi 21% di ossigeno per 3,5 ore. Interventi farmacologici possono essere introdotte a tempo debito e loro effetti studiato in cieco, randomizzati a blocchi della moda.

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

A Swine Model of Neonatal Asphyxia

Modelli animali di grandi dimensioni hanno buoni valori di traslazione nell&#39;esame della fisiologia e farmacologia di asfissia neonatale. Utilizzando suinetti appena nati, sviluppiamo un protocollo sperimentale per simulare asfissia neonatale che presenta i vantaggi di studiare l&#39;emodinamica sistemica e regionali, trasporti ossigeno con vie biochimiche e patologiche e correlazioni.

Un modello di asfissia neonatale suina

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

Research

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Medicine

14.2K Views.  University of Alberta. Modelli animali di grandi dimensioni hanno buoni valori di traslazione nell'esame della fisiologia e farmacologia di asfissia neonatale. Utilizzando suinetti appena nati, sviluppiamo un protocollo sperimentale per simulare asfissia neonatale che presenta i vantaggi di studiare l'emodinamica sistemica e regionali, trasporti ossigeno con vie biochimiche e patologiche e correlazioni.

Video: 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 modello di Piglet neonatale Hypoxic-ischemica Encefalopatia

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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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 neonatale mouse Spinal Cord Injury compressione Modello

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.

Infarto del miocardio in topi neonati, un modello di rigenerazione cardiaca

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 modello di Ischemia cardiaca cronica nei suini utilizzando un Constrictor Ameroid

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.

Cardiomiopatia tachicardia-indotta come un modello di insufficienza cardiaca cronica in maiali

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.

Lesione grave ustione in un modello di suina per valutazione clinica Dressing

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.

Misurazione di contrattilità isometrica dell'arteria mesenterica Mouse con filo Myography

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.

Istituzione di un modello suina di infarto post-miocardico per il trattamento delle cellule staminali

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.

Infarto miocardico mediante dispiegamento della bobina di embolizzazione percutanea in un modello suino

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 modello murino BALB/c neonatale di enterocolite necrotizzante

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