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

NOTA: Todos los procedimientos experimentales descritos en esta sección fueron aprobados por el Cuidado de Animales y el Comité Asesor de Investigación de la Universidad Católica de Lovaina Institucional (proyecto: 154/2013-B De Geest). 1. La ligadura permanente de la arteria coronaria descendente anterior <ol><li> Anestesiar el ratón por administración intraperitoneal de 40 mg / kg a 70 mg / kg de pentobarbital sódico. Asegúrese de que el ratón llega su plano adecuado de anestesia cuando ya no reacciona una pizca dedo del pie firme. Siempre confirme anestesia adecuada de esta manera antes de cualquier procedimiento quirúrgico o intervención. Utilice lubricante pomada oftálmica para evitar la sequedad de la córnea, mientras que bajo anestesia. Proporcionar analgesia preoperatoria 2-4 hr antes del inicio del procedimiento (buprenorfina 0,05 mg / kg SQ). <ol><li> Aplicar las técnicas de asepsia consistentes durante la cirugía supervivencia. Implementar procedimientos que inhiben a un microbiana con máximo grado posiblecontaminación de modo que la infección o la supuración significativa no se produce. Estos procedimientos incluyen el uso de instrumentos estériles y materiales estériles, la desinfección del área quirúrgica y la eliminación de la piel / pelo sobre el sitio quirúrgico y desinfección de este sitio. </li></ol></li><li> Intubar al ratón con una aguja roma de calibre 20 de elaboración propia. <ol><li> Ponga el ratón en posición supina con la hiperextensión de la cabeza. <ol><li> Enfocar la luz en la región del cuello. Levante la lengua con un pincet romo. La entrada de la laringe puede verse claramente. </li><li> Pasar la aguja roma a través de la laringe dentro de la tráquea bajo visión directa. Evaluar la intubación correcta conectando el ratón para el ventilador (volumen sistólico en l: 3 x peso corporal (g) + 155; frecuencia: 120 golpes por minuto). </li></ol></li><li> Por otra parte, mejorar la visualización de la intubación endotraqueal exponiendo primero atentamente la tráquea. <ol><li> Hacer una incisión de 5 mm mediados de cuello y retraertejido muscular justo por encima de la tráquea. </li><li> Realice la intubación usando un estereomicroscopio quirúrgico para la visualización directa de la tráquea. Levante la lengua e introduzca la aguja de calibre 20 auto-preparado embotado en la tráquea. Confirme intubación correcta conectando el ratón para el ventilador (volumen sistólico en l: 3 x peso corporal (g) + 155; frecuencia: 120 golpes por minuto). </li></ol></li></ol></li><li> Mantenga el ratón en posición supina y fijar el ratón con cinta. Realizar una cirugía en una almohadilla térmica para evitar la hipotermia. <ol><li> Afeitado y desinfectar la piel con Betadine. Tenga cuidado de que la extremidad posterior izquierda cruza la extremidad posterior derecha con el fin de obtener una vista mejor en el ventrículo izquierdo durante la cirugía. </li></ol></li><li> Hacer una pequeña incisión cutánea transversal hasta el esternón y separar la piel y los músculos subyacentes. </li><li> Tire de lado el m. pectoral menor y m. pectoral mayor con una sutura de seda 5-0. </li><li> Hacer una incision en el tercer espacio intercostal mediante la inserción de un pincet romo. </li><li> Mueva el pincet debajo de los músculos intercostales de lateral a medial hasta que se alcanza el esternón. Perforar la pared torácica empujando el pincet desde el interior a la piel. Complete la toracotomía cortando cuidadosamente el músculo intercostal justo por encima del pincet con una pequeña tijera. Utilice esta técnica para evitar la perforación de los pulmones. </li><li> Ponga una esponja sumergida en 0,9% de NaCl en la cavidad para proteger los pulmones. Introducir un esparcidor de la herida (retractor pecho) en el espacio intercostal para obtener la exposición del lado izquierdo del corazón. A partir de ahora, la aurícula izquierda, el ventrículo izquierdo y la arteria descendente anterior coronaria son visibles bajo el microscopio estereoscópico. </li><li> Realice una ligadura de la arteria descendente anterior coronaria con un solo 6-0 prolene ligadura sobre 1 mm por debajo de la punta de la aurícula izquierda. Esto es distal de la primera rama diagonal. NOTA: Como alternativa, 7-0 (00,05 mm de diámetro) o 8-0 roscas (0,04 mm de diámetro) se pueden utilizar. La aguja es una aguja Point círculo Taper C-1 13 mm 3/8. Ligadura exitosa de la arteria descendente anterior coronaria induce decoloración inmediata, lo que resulta en un miocardio aparece pálido en el territorio afectado. </li><li> Retire el separador de la herida (retractor en el pecho). <ol><li> Coloque tres 6-0 suturas Ti-Cron alrededor del espacio intercostal. Antes de apretar las suturas, retire la esponja de la cavidad torácica y volver a expandir los pulmones mediante el bloqueo de la salida del ventilador. Al hacerlo, los pulmones se vuelven a conectar con la pleura parietal. </li><li> Posteriormente, tirar de las suturas apretado y repetir reexpansión presionando hacia abajo en el pecho. Confirmar el cierre exitoso del tórax usando una pequeña cantidad de solución salina (no hay burbujas de aire deben considerarse cuando se aplica presión en el pecho). </li><li> Mira a través del músculo intercostal confirmar expansión normal de los pulmones. Vuelva a colocar los dos músculos pectorales, que actúa como unbarrera adicional para la prevención de un neumotórax. </li></ol></li><li> Cierre la piel con seda 5-0 suturas. </li><li> Desconecte el ratón del ventilador y permitir la recuperación sobre el cojín eléctrico. No deje a un animal sin vigilancia hasta que se haya recuperado el conocimiento suficiente para mantener decúbito esternal. No devuelva un animal que ha sido sometido a cirugía para la compañía de otros animales hasta que se recupere completamente. </li><li> Constantemente proporcionar analgesia postoperatoria (buprenorfina 0,05 mg / kg BID SQ durante al menos 48 horas después de la cirugía). </li></ol> 2. En vivo hemodinámico invasivo Mediciones en ratones <ol><li> Antes del procedimiento, sumergir el 1,0 francesa Millar catéter de presión en agua estéril a 37 ° C durante al menos 30 minutos para minimizar la deriva de la señal. Calibrar electrónicamente el sensor de presión a 0 mm Hg y 100 mm Hg y registrar datos en 2000 Hz. </li><li> Realizar la anestesia mediante la administración intraperitoneal de 1,4 g / kg de uretano. Compruebe queel ratón llega a su plano adecuado de anestesia cuando ya no reacciona una pizca dedo del pie firme. </li><li> Coloca el ratón anestesiado en posición supina. Asegure sus extremidades con cinta adhesiva. Mantenga la temperatura del cuerpo con una almohadilla térmica y monitor con una sonda rectal. Afeitarse la región del cuello y hacer una incisión en la línea media en la región del cuello para exponer la glándula tiroides. </li><li> Fijar el cuello con agujas dobladas. </li><li> Tire de un lado de la glándula salival y exponer la arteria carótida común derecha. El nervio vago, que se asemeja a un hilo blanco, se encuentra a lo largo de la arteria. Separe con cuidado la arteria carótida del nervio vago usando unas pinzas curvas. </li><li> Pasar un pinzas curvas debajo de la arteria carótida común derecha para separarlo de otros tejidos. Quitar el tejido conectivo alrededor de la arteria. </li><li> Pasar dos 6-0 cables de seda debajo de la arteria carótida común derecha. Hacer un nudo apretado en el alambre superior, que se coloca a la cabeza, cerrar y fijar con un Kocher (ligadura distal oclusiva). Pase el proxialambre mal dos veces de izquierda a derecha y fijar con 2 kochers (alambre no oclusiva proximal). </li><li> Mantenga la arteria carótida húmedo dejando caer un 0,9% de NaCl estéril. Seque el exceso de líquido con bastoncillos de algodón. </li><li> Hacer una incisión en la arteria carótida común derecha con una aguja de calibre 26 entre la ligadura distal y el alambre no oclusivo proximal. </li><li> Introducir el sensor de presión en la arteria. Verifique que no hay pérdida de sangre. Empuje suavemente el catéter de presión Millar 1.0 French adelante y ajustar el alambre no oclusiva proximal de tal manera que el catéter puede pasar cuidadosamente a través del cable por debajo de la clavícula. <ol><li> Minimizar la pérdida de sangre durante el ajuste del alambre no oclusivo proximal. No comprima el sensor de presión demasiado mientras avanzaba ya que es muy frágil. Como el hilo proximal no debe ocluir la arteria, el recipiente debe permanecer llena de sangre. </li></ol></li><li> Comience a grabar la señal de presión. Una señal de la presión arterial fluctuates en un ratón sano entre una presión diastólica de 60 a 70 mm Hg y una presión sistólica de 100 a 120 mm Hg. </li><li> Dirigir el catéter a través de la arteria innominada y a través de la aorta hacia el ventrículo izquierdo. La presión ventricular fluctúa entre 0 mm Hg y 100 a 120 mm Hg. Permitir que el catéter se estabilice el interior del ventrículo izquierdo. Grabar la señal durante 30 min a 60 min dependiendo de los requisitos experimentales. </li><li> Después de la terminación del experimento, en remojo el catéter en Alconox 1% durante 30 min. Lave el catéter con agua Milli-Q. Guarde el catéter en un bloque de espuma. </li><li> Recuperar datos del software de grabación para su posterior análisis. <ol><li> Para el análisis de datos, tenga en cuenta un intervalo de tiempo en que la señal de presión es estable. Elija por lo menos 10 ciclos cardíacos consecutivos de los datos registrados de interés. </li><li> Utilice software LabChart versión 8.0 o similar para analizar el ritmo cardíaco, la presión sistólica izquierda presión ventricular máxima, la mínima ventr izquierda diastólicapresión icular, la tasa pico de la contracción isovolumétrica ventricular izquierda (dP / dt max), la tasa pico de la relajación isovolumétrica ventricular izquierda (dP / dt min), la presión ventricular izquierda diastólica final, y la constante de tiempo de la ventricular izquierda isovolumétrica caída de presión (tau) 7. NOTA: La presión diastólica final corresponde a la presión en el punto de tiempo inmediatamente antes del aumento de la presión inducida por la contracción isovolumétrica. El cálculo de tau se basa en el ajuste de la presión ventricular izquierda en una curva de decaimiento monoexponencial, expresado como P (t) = p 0 e -t / tau + b, En esta fórmula, P (t) es la presión ventricular izquierda en el momento se ha llegado a t después de que el valor negativo máximo de dP / dt. El parámetro b corresponde a la asíntota teórico, que en un enfoque simplificado se puede suponer que es cero. Relajación isovolumétrica mejorada se traduce en un valor más pequeño de tau. </li></ol></li></ol&gt;

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None of the authors reports competing financial interests.

Cambios crónicos en la estructura y la función miocárdica, el desarrollo de la disfunción ventricular izquierda, y la progresión a la insuficiencia cardíaca pueden ser investigados en varios modelos murinos 12. La remodelación cardiaca y la disfunción puede ser inducida por lesión miocárdica o por sobrecarga de presión secundaria a la constricción de la aorta transversal, o pueden ser investigados en modelos genéticos de la miocardiopatía dilatada 12. Obviamente, el beneficio más pro...

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

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

La insuficiencia cardíaca es un síndrome en el que el corazón deja de bombear sangre a un ritmo acorde con las necesidades de oxígeno celular en reposo o durante el estrés. Se caracteriza por la retención de líquidos, falta de aliento, y la fatiga, en particular en el esfuerzo. La insuficiencia cardiaca es un problema creciente de salud pública, la principal causa de hospitalización, y una causa importante de mortalidad. La cardiopatía isquémica es la principal causa de insuficiencia cardíaca. Remodelación ventricular se refiere a cambios en la estructura, el tamaño, y la forma del ventrículo izquierdo. Esta remodelación arquitectónica del ventrículo izquierdo es inducida por lesión (por ejemplo, infarto de miocardio), por sobrecarga de presión (por ejemplo, hipertensión arterial sistémica o estenosis aórtica), o por sobrecarga de volumen. Desde la remodelación ventricular afecta el estrés de pared, tiene un profundo impacto en la función cardiaca y en el desarrollo de insuficiencia cardíaca. Un modelo de ligadura permanente de la descendin anterior izquierdag arteria coronaria en ratones se utiliza para investigar el remodelado ventricular y la función cardiaca después de un infarto de miocardio. Este modelo es fundamentalmente diferente en términos de objetivos y relevancia fisiopatológica en comparación con el modelo de la ligadura transitoria de la arteria descendente anterior coronaria. En este último modelo de lesión por isquemia / reperfusión, la medida inicial del infarto puede ser modulada por factores que afectan recuperación miocárdica después de la reperfusión. En contraste, la zona del infarto a las 24 horas después de la ligadura permanente de la arteria descendente anterior coronaria es fijo. La función cardiaca en este modelo se verá afectado por 1) el proceso de expansión del infarto, la curación del infarto, y la formación de cicatrices; y 2) el desarrollo concomitante de la dilatación ventricular izquierda, hipertrofia cardiaca, y remodelación ventricular. Además del modelo de ligadura permanente de la arteria descendente anterior coronaria, la técnica de mea hemodinámica invasivamedicio- en ratones se presenta en detalle.

El grado de infarto de miocardio puede ser evaluada por azul de Evans / cloruro de 2,3,5-trifeniltetrazolio (TTC) doble tinción. TTC es un indicador redox, que se convierte en 1,3,5-triphenylformazan-rojo profundo en los tejidos debido a la actividad de diversas deshidrogenasas en presencia de NADH 8 viviente. La figura 1 muestra una sección representativa del corazón a las 24 horas después de la ligadura de la arteria descendente anterior coronaria. Zonas azules manchados indican regione...

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

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

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

La ligadura permanente de la arteria coronaria descendente anterior en ratones: un modelo de remodelación post infarto de miocardio e insuficiencia cardiaca

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

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

Research

JoVE Journal

Medicine

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

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

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

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

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

Ligadura de las arterias coronarias y la inyección intramiocárdica en un modelo murino de infarto

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

Investigación

Medicina

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

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

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

La aplicación de la Permanente Ligadura arteria cerebral media en el ratón

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

Modified Technique for Coronary Artery Ligation in Mice

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

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

Técnica modificada para la ligadura de la arteria coronaria en ratones

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

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

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

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

Un modelo murino de isquemia-reperfusión miocárdica lesión a través de la ligadura de la arteria descendente anterior

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

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

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

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

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

Murino descendente anterior (LAD) ligadura de la arteria coronaria: un modelo mejorado y simplificado para el infarto de miocardio

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

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

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

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

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

Directa reimplantación de la arteria coronaria izquierda en la aorta en adultos con origen anómalo de la arteria coronaria izquierda desde la arteria pulmonar (ALCAPA)

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

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

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

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

Modelo de infarto de miocardio murino usando ligadura permanente de la arteria coronaria descendente anterior izquierda

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

Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major causes of mortality and morbidity around the world. Cell-based therapies for cardiac repair and improvement of left ventricular function after MI have attracted considerable attention. Accordingly, the safety and efficacy of these cell transplantations should be tested in a preclinical large animal model of HF prior to clinical use. Pigs are widely used for cardiovascular disease research due to their similarity to humans in terms of heart size and coronary anatomy. Therefore, we sought to present an effective protocol for the establishment of a porcine chronic HF model using closed-chest coronary balloon occlusion of the left circumflex artery (LCX), followed by rapid ventricular pacing induced with pacemaker implantation. Eight weeks later, the stem cells were administered by intramyocardial injection in the peri-infarct area. Then the infarct size, cell survival, and left ventricular function (including echocardiography, hemodynamic parameters, and electrophysiology) were evaluated. This study helps establish a stable preclinical large animal HF model for stem cell treatment.

We sought to establish a swine model of heart failure induced by left circumflex artery blockage and rapid pacing to test the effect and safety of intramyocardial administration of stem cells for cell-based therapies.

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 ...

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

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

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

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

Insuficiencia cardíaca de infarto post-miocárdico en el modelo de oclusión coronaria/reperfusión coronaria de pecho cerrado en Göttingen Minipigs y Cerdos Landrace

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

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

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

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

Generación y caracterización del infarto de miocardio del ventrículo derecho inducido por ligadura permanente de la arteria coronaria derecha en ratones

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