Los autores desean agradecer a los Institutos Canadienses de Investigación en Salud (MOP53116) y la Fundación del Patrimonio de Alberta para la investigación médica para la concesión de operación y financiar el establecimiento, respectivamente, para apoyar el desarrollo de este modelo experimental.

1. Anestesia <ol><li> Ajuste el caudal de la máquina de anestesia en 2L/min. Conecte el tubo de escape de succión al vacío. </li><li> Cargo máscara con gases anestésicos (isoflurano) en un 5% (~ 3 min). </li><li> Los lechones recién nacidos se inducirá con isoflurano inhalado 5% de oxígeno al 100% (~ 3 min). </li><li> Mantenimiento de la anestesia en un 2-3% de isoflurano. Ajuste fino de isoflurano en un 0,5% según el caso, sin embargo, puede variar de 0,5 a 5% dependiendo de la condición de los lechones. </li><li> Una vez que el acceso vascular se ha establecido, la anestesia inhalatoria se puede cambiar a anestesia intravenosa con fentanil (5-50 mcg / kg / h) y midazolam infusiones (200-500 mcg / kg / h). Pancuronio (50 a 100 mcg / kg / h) puede ser necesaria para controlar los movimientos excesivos del músculo durante la cirugía, mientras que la capacidad de observar el estado del animal se mantiene en el ajuste de los fármacos anestésicos. </li><li> El lechón es supervisado por la oximetría de pulso (saturación percutánea de oxígeno en el 95-100%) y ECG (frecuencia cardiaca en 130 a 170 latidos / min). </li><li> La temperatura rectal del lechón se mantiene a 38-40 º C con una manta de calefacción y calentador radiante. </li><li> El estado anestésico de los lechones se evalúan periódicamente durante todo el período experimental utilizando neurológicos (tamaño de la pupila, lagrimeo, movimientos corporales), conductuales (agitación), cardiovascular (taquicardia e hipertensión) y los parámetros respiratorios (taquipnea), según corresponda. Parálisis mínima se le da. La experiencia previa de la anestesia en los lechones con y sin parálisis sería útil para la evaluación. </li><li> El protocolo es un procedimiento no-supervivencia con la eutanasia de los animales al final del experimento con una sobredosis de pentobarbital (100 mg / kg) por vía intravenosa. </li></ol> 2. La colocación quirúrgica de catéteres vasculares en la ingle (Figura 1) <ol><li> Hacer un largo de 2-3cm incisión en la ingle derecha. </li><li> Diseccionar 1 cm de la venosa femoral derecha y 1 cm de la arteria femoral derecha. Coloque dos cuerdas alrededor de 3-0 cada buque. </li><li> Cateterización venosa femoral derecha: Ligar la parte distal de la vena. Insertar un catéter de Argyle (3,5 o 5 franceses, de doble lumen) (Covidien, Mansfield, MA) a 15 cm, siendo este lugar en la aurícula derecha. Ate las dos cadenas para asegurar el catéter. El catéter se puede usar para líquidos de mantenimiento y la infusión de medicamentos (puerto secundario) y venosa central / medición de la presión auricular derecha (puerto principal). </li><li> Cateterización arterial femoral derecho: Ligar la parte distal de la arteria. Levante la cadena proximal para detener el flujo de sangre. Insertar un catéter de Argyle (3,5 o 5 franceses, de una sola luz) a 5 cm. Esta acción coloca el catéter arterial en la aorta infra-renal de la medición continua de la presión arterial media y la extracción de sangre. Ate las dos cadenas para asegurar el catéter. </li><li> Cerca de la piel. </li></ol> 3. Establecer ventilación mecánica (Figura 2) <ol><li> Hacer un largo de 2-3cm incisión horizontal en el cuello. </li><li> Disección y exposición de 1 cm de la tráquea. Ponga dos cadenas 1-0 alrededor de la tráquea. </li><li> Insertar un tubo endotraqueal (3.0 o 3.5) a 1 cm en la tráquea. Conectarse a un respirador artificial y comenzar la ventilación mecánica. Asegure el tubo endotraqueal. </li><li> Diseccionar y exponer la arteria carótida común. Rodean el buque con una sonda de ultrasonido el tiempo de tránsito del flujo (2SB o 2RB, Transonic Systems Inc., Ithica, NY) para medir continuamente el flujo de sangre. </li></ol> 4. Colocación de sondas de flujo a mesentérica superior (Figura 3) y renal izquierda (Figura 4) las arterias <ol><li> Dosis adicionales de fentanilo (5-10 mcg / kg) y acepromacina (0,01-0,02 mg / kg) son obligatorios antes de la incisión de la piel. </li><li> Hacer una larga incisión subcostal flanco y diseccionar cuidadosamente las capas musculares. </li><li> Exponer la aorta abdominal. </li><li> Minimizar la manipulación vascular (vasoespasmo) y lesiones linfático. </li><li> Diseccionar 0.5-1cm arteria mesentérica superior y poner una sonda de flujo Transonic (3SB) a su alrededor. </li><li> Diseccionar 0.5-1cm arteria renal izquierda y poner una sonda de flujo Transonic (2SB) a su alrededor. </li><li> Cerca de la piel y seguro que la sonda de flujo. </li></ol> 5. Colocación de catéter de arteria pulmonar (Figura 5) y caudal de la sonda (Figura 6) <ol><li> Dosis adicionales de fentanilo (5-10 mcg / kg) y acepromacina (0,01-0,02 mg / kg) son obligatorios antes de la incisión de la piel. </li><li> Se encuentran los animales en la posición de lateral derecho. </li><li> Toracotomía en el cuarto espacio intercostal izquierdo. </li><li> Tenga cuidado con la arteria mamaria interna y la vena, si es necesario ligar. </li><li> Use un hisopo dental para presionar hacia abajo el pulmón izquierdo y el aumento de oxígeno según sea necesario. </li><li> Abrir el pericardio. </li><li> Identificar el conducto arterioso, que va desde la arteria pulmonar con la aorta. </li><li> Ductus arterioso puede ligarse mediante la colocación de un clip o por una gruesa &quot;3-O de la seda&quot; empate en su origen. </li><li> Libre de la arteria pulmonar principal y pasar avhonda ascular con un grosor &quot;0&quot; empate. </li><li> Realice una bolsa de tabaco (5-0 Prolene) de sutura en la base para la colocación de catéter de arteria pulmonar. </li><li> Inserte un 20G angiocath (con 3 orificios laterales a menos de 1 cm desde la punta del catéter) a través de la bolsa de tabaco a un máximo de 1 cm. </li><li> Compruebe que el libre flujo de la sangre venosa. </li><li> Conectarse a un transductor de presión, control de la presión arterial pulmonar y la forma de onda. </li><li> Apriete la bolsa de tabaco y asegurar el catéter pulmonar. </li><li> Colocar una sonda de flujo Transonic (6SB) alrededor de la arteria pulmonar principal. </li><li> Coloque el gel ultrasónico entre la sonda de flujo y de la arteria para permitir que para la transducción de señal óptima. </li><li> Cubra la herida con una gasa húmeda salina. </li></ol> 6. La hipoxia y reoxigenación protocolo <ol><li> Disminuir la concentración de oxígeno inspirado del 10% al aumentar la concentración de nitrógeno gaseoso inhalado para inducir a la hipoxemia. </li><li> Ajustar la concentración de oxígeno inspirado entre 10% y 15% para obtener una PaO 2 de 20-40 mmHg o SaO 2 de 30-40% durante 2 horas. </li><li> Realizar un análisis de sangre arterial para evaluar la PaCO 2 y ajustar la velocidad del ventilador en consecuencia. </li><li> Con la inducción de la hipoxemia, la primera hora se dedica a la inducción de una taquicardia constante (y el gasto cardíaco) respuesta. </li><li> Continuará monitoreando los cambios en el flujo sanguíneo en la arteria carótida común, mesentérica superior y la izquierda las arterias renales. </li><li> Durante la segunda hora de la hipoxia, el estrés hipóxico es mayor para reducir progresivamente el gasto cardíaco al 30-40% del valor basal, presión arterial media de 30 a 35 mmHg y pH arterial 6,95 a 7,05. </li><li> Estrés hipóxico puede ser terminado prematuramente o ampliarse en 15 min, según corresponda. </li><li> Aumentar la concentración de oxígeno inspirado abruptamente al 100% por la interrupción abrupta de gas nitrógeno, sin dejar de oxígeno puro. </li><li> Monitorear el gasto cardiaco, presión arterial media y otros parámetros hemodinámicos para una rápida recuperación. </li><li> Reanimación con oxígeno al 100% se puede continuar por 0.5h. Después de este período de tiempo, reducir la concentración de oxígeno inspirado rápidamente al 21%. </li><li> Continuar con la reoxigenación del 21% de oxígeno para el resto del período del experimento. La concentración de oxígeno inspirado se puede valorar a un 25% si es necesario. </li><li> Bolos de líquido de 10 ml / kg de solución de Ringer lactato puede ser necesaria en su caso durante el período experimental. Su uso debe ser protocolizado. </li></ol> 7. Los resultados representativos: La inducción de la hipoxemia en el lechón recién nacido durante la primera hora de la hipoxia debe aumentar el gasto cardiaco (flujo arterial pulmonar) al 120% -130% del valor basal (Figura 7) y la frecuencia cardiaca (Figura 7). Por lo general, el gasto cardíaco debe alcanzar su pico de compensación entre la primera y la 1h 0.5h de la hipoxia. Además, el flujo de sangre debe ser centralizado que resulta en disminución de la perfusión renal y mesentérico pero conservado o aumentado el flujo de la arteria carótida común (Figura 8). Durante la segunda hora de la hipoxia, hay una disminución constante del gasto cardíaco, el desarrollo de hipotensión (Figura 9), la desaceleración de la frecuencia cardíaca con o sin arritmia ocurrió. Hipoxia debe inducir a la hipertensión pulmonar con aumento de la presión arterial pulmonar (Figura 9), que a veces puede disminuir en los últimos 30 min de hipoxia a medida que disminuye el gasto cardíaco. Tras la reanimación, todos los parámetros hemodinámicos de inmediato se recuperará con el inicio normoxic, a excepción del flujo sanguíneo renal que poco a poco se recupera durante la primera hora de reoxigenación. Sin embargo, los parámetros hemodinámicos, especialmente para el gasto cardíaco y la presión arterial media se deteriora gradualmente durante las primeras 2 horas de la reoxigenación de cerca de 70-75% del valor basal normoxic y 35-45 mmHg, respectivamente. Esta disfunción cardiovascular por lo menos en parte, por el aturdimiento miocárdico y garantiza tratamientos cardiovasculares de apoyo tales como vasoactivos e inotrópicos. <img alt="Figura 1" src="/files/ftp_upload/3166/3166fig1.jpg" /> Figura 1: en la ingle de la incisión con la colocación de catéteres femorales arterial y venosa <img alt="Figura 2" src="/files/ftp_upload/3166/3166fig2.jpg" /> Figura 2: incisión en el cuello con la colocación de un tubo endotraqueal y una sonda de flujo alrededor de la arteria carótida común <img alt="Figura 3" src="/files/ftp_upload/3166/3166fig3.jpg" /> Figura 3: en el flanco de la incisión con el aislamiento de la arteria mesentérica superior <img alt="Figura 4" src="/files/ftp_upload/3166/3166fig4.jpg" /> Figura 4: flanco de la incisión con el aislamiento de la arteria renal izquierda <img alt="Figura 5" src = &quot;/ files/ftp_upload/3166/3166fig5.jpg&quot; /&gt; Figura 5: La toracotomía con la colocación de catéter de arteria pulmonar <img alt="Figura 6" src="/files/ftp_upload/3166/3166fig6.jpg" /> Figura 6: La toracotomía con la colocación de una sonda de flujo Transonic alrededor de la arteria pulmonar principal <img alt="Figura 7" src="/files/ftp_upload/3166/3166fig7.jpg" /> Figura 7: Los cambios temporales en (A) el gasto cardiaco (flujo arterial pulmonar) y (B) de la frecuencia cardíaca durante la hipoxia y reoxigenación <img alt="Figura 8" src="/files/ftp_upload/3166/3166fig8.jpg" /> Figura 8: Los cambios temporales en el flujo de sangre en (A) carótida común, (B) y la mesentérica superior (C) las arterias renal izquierda durante la hipoxia y reoxigenación <img alt="Figura 9" src="/files/ftp_upload/3166/3166fig9.jpg" /> Figura 9: Los cambios temporales en (A) la presión arterial media y (B) la presión arterial pulmonar durante la hipoxia y reoxigenación

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No hay conflictos de interés declarado.

El protocolo experimental actual tiene una ventaja para examinar los cambios hemodinámicos sistémicos y regionales en temas neonatal durante el proceso de hipoxia y reoxigenación. También puede examinar el efecto correspondiente de las intervenciones utilizadas para mejorar la función cardiovascular durante la recuperación. Nosotros y otros han informado de la experiencia y los resultados en el estudio de la asfixia neonatal respecto a los efectos cardiovasculares de 1, 2 pulmonares, neurológicos ...

a swine model of neonatal asphyxia

Anualmente más de 1 millón de recién nacidos mueren en el mundo en relación a la asfixia. Recién nacidos asfixiados suelen tener un fallo multiorgánico, incluyendo hipotensión, déficit de perfusión, la encefalopatía hipóxico-isquémica, hipertensión pulmonar, enterocolitis vasculopática, insuficiencia renal y las complicaciones tromboembólicas. Los modelos animales se han desarrollado para ayudarnos a comprender la fisiopatología y farmacología de la asfixia neonatal. En comparación con los roedores y los corderos recién nacidos, los lechones recién nacidos ha demostrado ser un valioso modelo. El lechón recién nacido tiene varias ventajas, incluyendo el desarrollo similar a la de 36 a 38 semanas el feto humano con los sistemas del cuerpo comparable, el tamaño corporal grande (~ 1,5-2 kg al nacer) que permite la instrumentación y el seguimiento de los animales y el control de las variables de confusión alteraciones hemodinámicas y la hipoxia. Se describen un protocolo experimental para simular asfixia neonatal y nos permite examinar los cambios hemodinámicos sistémicos y regionales durante el proceso de asfixia y reoxigenación, así como los respectivos efectos de las intervenciones. Además, el modelo tiene la ventaja de estudiar un fallo multiorgánico o disfunción de forma simultánea y la interacción con varios sistemas del cuerpo. El modelo experimental es un procedimiento no-supervivencia que consiste en la instrumentación quirúrgica de los lechones recién nacidos (1-3 días de edad y de 1.5 a 2.5 kg de peso, de raza mixta) para permitir el establecimiento de ventilación mecánica, vascular (arterial y venosa central) el acceso y la colocación de catéteres y sondas de flujo (Transonic Inc.) para el seguimiento continuo de la presión intra-vascular y el flujo sanguíneo a través de las arterias carótidas principales diferentes, incluyendo pulmonar, común, mesentérica superior y la izquierda las arterias renales. El uso de estos lechones cirugía instrumentada, después de la estabilización de 30-60 minutos como se define por la variación de Z &lt;10% en los parámetros hemodinámicos y los gases sanguíneos normales, se iniciará un protocolo experimental de hipoxemia grave que es inducida por la hipoxia alveolar normocápnicos. El lechón se ventila con un 10-15% de oxígeno al aumentar la concentración inhalada de gas nitrógeno durante 2 horas, con el objetivo de saturación arterial de oxígeno del 30-40%. Este grado de hipoxemia se produce la asfixia clínica con acidosis metabólica severa, hipotensión sistémica y shock cardiogénico con hipoperfusión de los órganos vitales. La hipoxia es seguido por la reoxigenación con oxígeno al 100% de 0.5h y 21% de oxígeno para 3.5h. Las intervenciones farmacológicas pueden ser introducidos en su momento y sus efectos investigados en un estudio ciego, aleatorizado en bloques de la moda.

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

A Swine Model of Neonatal Asphyxia

Modelos de animales grandes tienen buenos valores de traslación en el examen de fisiología y farmacología de la asfixia neonatal. Utilizando los lechones recién nacidos, desarrollamos un protocolo experimental para simular asfixia neonatal que tiene ventajas de estudiar la hemodinámica sistémica y regional, el transporte de oxígeno a las vías bioquímicas y patológicas y correlaciones.

Un modelo porcino de la asfixia neonatal

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

Research

JoVE Journal

Medicine

14.2K vistas.  University of Alberta. Modelos de animales grandes tienen buenos valores de traslación en el examen de fisiología y farmacología de la asfixia neonatal. Utilizando los lechones recién nacidos, desarrollamos un protocolo experimental para simular asfixia neonatal que tiene ventajas de estudiar la hemodinámica sistémica y regional, el transporte de oxígeno a las vías bioquímicas y patológicas y correlaciones.

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 modelo del cochinillo de Neonatología encefalopatía hipóxico-isquémica

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

Investigación

Medicina

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 ratón neonatal lesión de médula espinal de compresión Modelo

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.

El infarto de miocardio en ratones recién nacidos, un modelo de regeneración 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 modelo de isquemia cardíaca crónica en cerdos usando 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.

Cardiomiopatía Taquicardia-inducida como un modelo de insuficiencia cardíaca crónica en porcino

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.

Quemaduras severas en un modelo porcino para la preparación clínica evaluación

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.

Medición de la contractilidad isométrica de la arteria mesentérica de ratón con cable miografía

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.

Establecer un modelo porcino de infarto de infarto post-miocardio insuficiencia cardíaca para el tratamiento de células madre

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 de miocardio por despliegue de bobina de embolización percutánea en un modelo porcino

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 modelo de ratón BALB/c neonatal de enterocolitis necrosante

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