Este estudio fue apoyado por el Fondo de Médico-Científico de la Alcaldía de la ciudad de Viena y biocirugía Ethicon, Inc. New Jersey, EE.UU.. Los autores expresan su agradecimiento al Profesor Heber Ferraz-Leite, Director del &quot;Taller Europeo sobre Microcirugía y revascularización cerebral en la Universidad Médica de Viena, Austria, por su enseñanza valiosa de microcirugía.

1. Colocación y preparación del animal Los experimentos fueron aprobados por el responsable del comité de ética local y realizado de acuerdo con las directrices de FELASA. <ol><li> Inicio anestesia general de la mujer de Nueva Zelandia conejo blanco (2.5 a 3.5 kg) con la inyección intramuscular de ketamina (30mg/kg) y xilazina (6mg/kg) y continuar después de la intubación mecánica (diámetro del tubo de 4 mm, longitud 18 mm) con anestesia de gas ( ) isoflurano en la monitorización del ECG. Realizar un control del dolor a través de una pizca pie los 15 minutos, y adaptar la anestesia en caso de respuesta positiva. </li><li> Fijar el conejo en posición de decúbito supino sobre una placa de bodywarm. </li><li> Prepare el área de la cirugía por la eliminación de cabello que van desde el ángulo de la mandíbula hasta la mitad del tórax. Realizar todos los procedimientos en condiciones estériles. </li></ol> 2. Preparación de la vena yugular externa <ol><li> Realizar una incisión desde el ángulo de la mandíbula hasta el manubrio del esternón. </li><li> Con el microscopio, seleccione un segmento de 1 cm de largo de la vena yugular externa izquierda sin ramas venosas y aislarlo microcirugía (Figura 1a). Durante toda la operación con frecuencia se aplican 4% papaverina solución de HCl y la solución de antibiótico (neomicina sulfato de 5mg/ml) por vía tópica en los vasos y las anastomosis para prevenir las infecciones vasoespasmo y local. </li><li> Ligar la vena proximal y distal con sutura polyfilament 4-0 (Vicryl, Ethicon Inc, New Jersey, EE.UU.), a continuación, resecar y mantenerlo en solución salina heparinizada (1000 UI de heparina en 20 ml de solución salina al 0,9% y 1 ml de HCl 4% papaverina ). </li></ol> 3. Preparación de las dos arterias carótidas comunes (ACC) <ol><li> Prepare un segmento de la izquierda CCA se extiende desde la bifurcación carotídea hasta el arco aórtico. Preservar hasta donde sea posible ramas arteriales corriendo en sentido medial y el suministro de estructuras de la laringe y la tráquea, así como todas las estructuras neurales. </li><li> Prepare el derecho de CCA. Movilizarla hasta la bifurcación de la carótida y por el tronco bracchiocephalic. </li><li> Administrar 1.000 UI de heparina por vía intravenosa. </li><li> Clip de la derecha CCA temporalmente justo debajo de la bifurcación de la carótida. </li><li> Ligar el derecho CCA proximal directamente sobre el tronco braquiocefálico. Cortar el derecho CCA sobre la ligadura y regar el muñón con solución salina heparinizada. </li><li> Cortar y extirpar cuidadosamente la adventicia en el extremo libre del derecho CCA. Libre meticulosamente el segmento de la izquierda CCA prevista para la anastomosis de la adventicia y el clip que distal y proximal. </li></ol> 4. Anastomosis de ambas evaluaciones comunes <ol><li> Realizar una arteriotomía elíptica de la izquierda CCA entre los clips de acuerdo con el tamaño de la anastomosis planeado con el derecho de la CCA y la bolsa venosa. Riego de la izquierda CCA con solución salina heparinizada. (Figura 1b) </li><li> Sutura de la circunferencia posterior del derecho CCA-muñón en la arteriotomía de la izquierda CCA, con cuatro a cinco organizaciones no reabsorbible monofilamento 10-0 (10-0 Ethilon, Ethicon Inc, New Jersey, EE.UU.). </li><li> Haga un corte longitudinal en el muñón de la derecha CCA para adaptarse a la mitad de la circunferencia de la bolsa venosa. Anastomosis de la parte de atrás de la pared venosa primera bolsa con la arteriotomía en la izquierda CCA, utilizando de nuevo 4-5 10-0. A continuación, se anastomosan la parte posterior de la bolsa venosa con la parte posterior de la derecha CCA con 3 a 4 puntos de sutura. (Figura 1c) </li><li> Realizar la anastomosis en el mismo orden en el lado anterior. (Figura 1d) </li><li> Retire el clip distal a la derecha del CCA. El aneurisma no suele ser completamente sellado, por lo tanto, lavar el aire atrapado y los desechos. </li><li> Sello de las líneas de sutura alrededor de la anastomosis y el cuello del aneurisma con una almohadilla de grasa y pegamento de fibrina (Evicel, Ethicon Inc. biocirugía, Nueva Jersey, EE.UU.). Quite los clips restantes. </li><li> Use 4-0 suturas reabsorbibles (Monocryl, Ethicon Inc, New Jersey, EE.UU.) para suturas interrumpidas por vía subcutánea y luego de una sutura cutáneo en funcionamiento. </li></ol> 5. El manejo postoperatorio <ol><li> Administrar 10 mg / kg de ácido acetilsalicílico por vía intravenosa, y 60 ml de glucosa al 5% por vía subcutánea. </li><li> Aplicar parches transdérmicos de fentanilo matriz de la liberación de 12,5 mg / hora en la región del cuello afeitado de los animales para la analgesia eficaz durante 72 horas. </li><li> Administrar 250 UI / kg de heparina de bajo peso molecular por vía subcutánea diariamente durante 2 semanas. </li></ol> 6. Los resultados representativos: Si el procedimiento se realiza correctamente, el aneurisma se quedará patente y los animales se recuperan en unos 3 días. En nuestra experiencia, un procedimiento de imagen se debe hacer como mínimo una semana más tarde. De lo contrario los animales, posiblemente, no va a tolerar el procedimiento y se podrían perder. Para la embolización, le recomendamos que esperar alrededor de 4 semanas de garantizar compleendotelización te del aneurisma neck.Using las técnicas presentadas y la gestión de los autores podría llegar a la permeabilidad de un aneurisma en el 85,7% y la mortalidad no en su serie publicada recientemente 14. Para minimizar el alto índice de denuncias de complicaciones intestinales de hasta un 20%, 12 que siempre un prolongado tratamiento postoperatorio analgésico de la analgesia de 72 horas comparado con el tratamiento de rutina analgesia.This 24 horas se intensificó no dio lugar a complicaciones gástricas. El manejo de la anticoagulación agresiva es importante llegar a los índices de permeabilidad suficiente aneurisma. Esto va junto con los resultados de Grunwald et al. mostrando los efectos positivos de la anticoagulación combinada. 17 A causa de la anticoagulación agresiva, es fundamental contar con un sellado eficaz de la anastomosis. Hicimos muy buena experiencia con nuevos pegamento de fibrina (Evicel, Ethicon Inc. biocirugía, Nueva Jersey, EE.UU.). Además se recomienda utilizar conejos pequeños (un máximo de 3,5 kg), como en nuestra experiencia las complicaciones suelen estar relacionados con los sujetos con sobrepeso.

<ol>
	<li>Molyneux, A., Kerr, R., Yu, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=International+subarachnoid+aneurysm+trial+(ISAT)+of+neurosurgical+clipping+versus+endovascular+coiling+in+2143+patients+with+ruptured+intracranial+aneurysms:+a+randomised+comparison+of+effects+on+survival,+dependency,+seizures,+rebleeding,+subgroups,+and+aneurysm+occlusion.">International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion.</a> Lancet. 366, 809-817 (2005).</li><li>Mitchell, P., Kerr, R., Mendelow, A., Molyneux, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Could+late+rebleeding+overturn+the+superiority+of+cranial+aneurysm+coil+embolization+over+clip+ligation+seen+in+the+International+Subarachnoid+Aneurysm+Trial.">Could late rebleeding overturn the superiority of cranial aneurysm coil embolization over clip ligation seen in the International Subarachnoid Aneurysm Trial.</a> J Neurosur. 108, 437-442 (2008).</li><li>Bavinzski, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histopathological+findings+in+experimental+aneurysms+embolized+with+conventional+and+thrombogenic/antithrombolytic+Guglielmi+coils.">Histopathological findings in experimental aneurysms embolized with conventional and thrombogenic/antithrombolytic Guglielmi coils.</a> Minim Invasive Neurosurg. 42, 167-174 (1999).</li><li>Bocher-Schwarz, H. 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Review of surgically constructed models and their laboratory applications.</a> Neurorad. 36, 537-546 (1994).</li><li>Anidjar, S., Salzmann, J., Gentric, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elastase+induced+experimental+aneurysms+in+rats.">Elastase induced experimental aneurysms in rats.</a> Circulation. 82, 973-981 (1990).</li><li>Wakhloo, A., Schellhammer, F., de Vries, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-expanding+and+balloon-expandable+stents+in+the+treatment+of+carotid+aneurysms:+an+experimental+study+in+a+canine+model.">Self-expanding and balloon-expandable stents in the treatment of carotid aneurysms: an experimental study in a canine model.</a> AJNR. 15, 493-502 (1994).</li><li>Dai, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histopathologic+and+immunohistochemical+comparison+of+human,+rabbit,+and+swine+aneurysms+embolized+with+platinum+coils.">Histopathologic and immunohistochemical comparison of human, rabbit, and swine aneurysms embolized with platinum coils.</a> AJNR Am J Neuroradiol. 26, 2560-2568 (2005).</li><li>Shin, Y. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Creation+of+four+experimental+aneurysms+with+different+hemodynamics+in+one+dog.">Creation of four experimental aneurysms with different hemodynamics in one dog.</a> AJNR. 26, 1764-1767 (2005).</li><li>Abruzzo, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histologic+and+morphologic+comparison+of+experimental+aneurysms+with+human+intracranial+aneurysms.">Histologic and morphologic comparison of experimental aneurysms with human intracranial aneurysms.</a> AJNR Am J Neuroradiol. 19, 1309-1314 (1998).</li><li>Bavinzski, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+bifurcation+aneurysm:+a+model+for+in+vivo+evaluation+of+endovascular+techniques.">Experimental bifurcation aneurysm: a model for in vivo evaluation of endovascular techniques.</a> Minim Invasive Neurosurg. 41, 129-132 (1998).</li><li>Spetzger, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microsurgically+produced+bifurcation+aneurysms+in+a+rabbit+model+for+endovascular+coil+embolization.">Microsurgically produced bifurcation aneurysms in a rabbit model for endovascular coil embolization.</a> J Neurosurg. 85, 488-495 (1996).</li><li>Sherif, C., Marbacher, S., Erhardt, S., Fandino, J., J, . <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+microsurgical+creation+of+venous-pouch+arterial-bifurcation+aneurysms+in+rabbits.">Improved microsurgical creation of venous-pouch arterial-bifurcation aneurysms in rabbits.</a> AJNR. , .</li><li>Marbacher, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complex+Bi-Lobular,+Bi-Saccular,+and+Broad-Necked+Microsurgical+Aneurysms+Formation+in+the+Rabbit+Bifurcation+Model+for+the+Study+of+Upcoming+Endovascular+Techniques.">Complex Bi-Lobular, Bi-Saccular, and Broad-Necked Microsurgical Aneurysms Formation in the Rabbit Bifurcation Model for the Study of Upcoming Endovascular Techniques.</a> AJNR. , .</li><li>Sherif, C., Plenk, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+angiographic+and+histopathologic+evaluation+of+experimental+aneurysms.">Quantitative angiographic and histopathologic evaluation of experimental aneurysms.</a> AJNR. , .</li><li>Grunwald, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anticoagulation+regimes+and+their+influence+on+the+occlusion+rate+of+aneurysms:+an+experimental+study+in+rabbits.">Anticoagulation regimes and their influence on the occlusion rate of aneurysms: an experimental study in rabbits.</a> Neurosurg. 57, 1048-1054 (2005).</li><li>Forrest, M. D., O'Reilly, G. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+experimental+aneurysms+at+a+surgically+created+arterial+bifurcation.">Production of experimental aneurysms at a surgically created arterial bifurcation.</a> AJNR Am J Neuroradiol. 10, 400-402 (1989).</li></ol>

Los autores recomiendan a consideración los siguientes pasos quirúrgicos críticos clave para lograr buenos resultados y los aneurismas de patente: <ol><li> Disección cuidadosa de un largo segmento de la izquierda CCA para la anastomosis fácil, sin destrucción de los nervios y los vasos pequeños. </li><li> La extracción cuidadosa de los tejidos fibrosos altamente trombogénicos periadventicia antes de la creación de la anastomosis. </li><li> Creación de una anastomosis sin tensión. </li><li> Menos suturas:...

<table border="1"><tbody><tr><th> Nombre del reactivo </th><th> Empresa </th><th> Número de catálogo </th><th> Comentarios </th></tr><tr><td> Vicryl4-0 polyfilament suturas recuperables </td><td> Ethicon Inc </td><td> J386H </td><td></td></tr><tr><td> Ethilon 10-0 monofilamento reabsorbible suturas no </td><td> Ethicon Inc </td><td> 2814 </td><td> aguja de punta cónica </td></tr><tr><td> Evicel BioGlue </td><td> Ethicon Inc. biocirugía </td><td> 3901 </td><td></td></tr><tr><td> Fentanilo parche dérmico 12,5 mg / h </td><td></td><td></td><td> Cualquier genericon </td></tr><tr><td> Heparina </td><td></td><td></td><td> Cualquier genericon </td></tr><tr><td> Salina al 0,9% </td><td></td><td></td><td> Cualquier genericon </td></tr><tr><td> 4% papaverina HCl </td><td></td><td></td><td> Cualquier genericon </td></tr><tr><td> Neomicina sulfato de 5 mg / ml </td><td></td><td></td><td> Cualquier genericon </td></tr><tr><td> Ketamina 50mg/ml </td><td></td><td></td><td> Cualquier genericon </td></tr><tr><td> Xilazina 20mg/ml </td><td></td><td></td><td> Cualquier genericon </td></tr></tbody></table>

microsurgical venous pouch arterial-bifurcation aneurysms in the rabbit model: technical aspects

Por rotura de aneurismas cerebrales humanos embolización endovascular se ha convertido en una alternativa equivalente a un recorte del aneurisma. 1 Sin embargo, los grandes ensayos clínicos han demostrado decepcionantes resultados a largo plazo con inaceptables altas tasas de recanalización del aneurisma y la rotura de un aneurisma retraso. 2 Para superar estos problemas, estudios en animales de experimentación son cruciales para el desarrollo de mejores dispositivos endovasculares 3-5. Varios modelos animales en ratas, conejos, perros y cerdos están disponibles. 8.6 Las comparaciones de los diferentes modelos animales demostró la superioridad del modelo de conejo con respecto a la hemodinámica y la comparabilidad del sistema de coagulación y la rentabilidad. 9-11 El modelo de bolsa de bifurcación arterial venosa en conejos está formado por una bolsa venosa sutura en una bifurcación creado artificialmente el caso de las dos arterias carótidas comunes (CCA). La principal ventaja de este modelo son verdaderas hemodinámica bifurcational. 12 Los principales inconvenientes son las exigencias de microcirugía hasta la fecha se alto nivel técnico y una alta morbilidad y mortalidad de hasta un 50%. 13 Estas limitaciones se han traducido en un menor uso frecuente de este modelo de aneurisma en el reciente años. Estas deficiencias podrían superarse con la mejora de los procedimientos quirúrgicos y modificado peri-y postoperatorio analgésico y anticoagulante. 14-16 Nuestras técnicas se informa en este trabajo demuestran que esta técnica optimizada para la creación de microcirugía de los aneurismas de la bifurcación arterial.

Watch this Scientific Journal Video about Microsurgical Venous Pouch Arterial-Bifurcation Aneurysms in the Rabbit Model: Technical Aspects at JoVE.com

Microsurgical Venous Pouch Arterial-Bifurcation Aneurysms in the Rabbit Model: Technical Aspects

Una técnica optimizada para la creación de microcirugía de los aneurismas de la bifurcación arterial imitando bifurcación aneurisma cerebral humana se describe. Una bolsa venosa se sutura en una bifurcación creado artificialmente el caso de las dos arterias carótidas comunes. Facilitó las técnicas microquirúrgicas y la anticoagulación agresiva postoperatorio y analgesia conducir a minimizar las tasas de morbilidad y altas tasas de permeabilidad de un aneurisma.

Microcirugía venosa bolsa arterial-Bifurcación Los aneurismas en el modelo de conejo: Aspectos Técnicos

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.1 However, large clinical trials ...

microsurgical-venous-pouch-arterial-bifurcation-aneurysms-rabbit

Research

JoVE Journal

Medicine

13.9K vistas.  Hospital Rudolfstiftung. Una técnica optimizada para la creación de microcirugía de los aneurismas de la bifurcación arterial imitando bifurcación aneurisma cerebral humana se describe. Una bolsa venosa se sutura en una bifurcación creado artificialmente el caso de las dos arterias carótidas comunes. Facilitó las técnicas microquirúrgicas y la anticoagulación agresiva postoperatorio y analgesia conducir a minimizar las tasas de morbilidad y altas tasas de permeabilidad de un aneurisma....

Video: Microsurgical Venous Pouch Arterial-Bifurcation Aneurysms in the Rabbit Model: Technical Aspects

Technical Aspects of the Mouse Aortocaval Fistula

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta and inferior vena cava (IVC) are exposed. The proximal infrarenal aorta and the distal aorta are dissected for clamp placement and needle puncture, respectively. Special attention is paid to avoid dissection between the aorta and the IVC. After clamping the aorta, a 25 G needle is used to puncture both walls of the aorta into the IVC. The surrounding connective tissue is used for hemostatic compression. Successful creation of the AVF will show pulsatile arterial blood flow in the IVC. Further confirmation of successful AVF can be achieved by post-operative Doppler ultrasound.

The goal is to produce an arteriovenous fistula that is simple and reproducible. This method does not use sutures or glue adhesive. Therefore the samples can be used with the least amount of foreign materials for analysis.

Aspectos técnicos de la aortocava Fístula Ratón

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta ...

Investigación

Medicina

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms.
Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions.
The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat&#39;s descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta.
We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat.

Microsurgical sidewall aneurysms in rats are created by end-to-side anastomosis of an aortic graft to the abdominal aorta. We present step-by-step instructions and discuss anatomical and surgical details for successful experimental saccular aneurysm creation.

El Helsinki Rata microquirúrgica flanco Aneurisma Modelo

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced ...

The Rabbit Blood-shunt Model for the Study of Acute and Late Sequelae of Subarachnoid Hemorrhage: Technical Aspects

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH.
This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

The experimental intracranial pressure-controlled blood shunt subarachnoid hemorrhage (SAH) model in the rabbit combines the standard procedures &#8212; subclavian artery cannulation and transcutaneous cisterna magna puncture, which enables close mimicking of human pathophysiological conditions after SAH. We present step-by-step instructions and discuss key surgical points for successful experimental SAH creation.

El Conejo Modelo Blood-shunt para el Estudio de la aguda y secuelas tardías de Hemorragia subaracnoidea: Aspectos Técnicos

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and ...

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to atherosclerotic plaque development or the rupturing of established plaques, interrupts normal blood flow leading to various morbidities such as myocardial infarction and stroke. In the clinic endovascular procedures such as angioplasty are commonly performed to reopen the lumen. However, these treatments inevitably damage the vessel wall as well as the vascular endothelium, triggering an excessive healing response and the development of a neointimal plaque that extends into the lumen causing vessel restenosis (re-narrowing). Restenosis remains a major cause of failure of endovascular treatments for atherosclerosis. Thus, preclinical animal models of restenosis are vitally important for investigating the pathophysiological mechanisms as well as translational approaches to vascular interventions. Among several murine experimental models, femoral artery wire injury is widely accepted as the most suitable for studies of post-angioplasty restenosis because it closely resembles the angioplasty procedure that injures both endothelium and vessel wall. However, many researchers have difficulty utilizing this model due to its high degree of technical difficulty. This is primarily because a metal wire needs to be inserted into the femoral artery, which is approximately three times thinner than the wire, to generate sufficient injury to induce prominent neointima. Here, we describe the essential surgical details to effectively overcome the major technical difficulties of this model. By following the presented procedures, performing the mouse femoral artery wire injury becomes easier. Once familiarized, the whole procedure can be completed within 20 min.

The mouse femoral artery wire injury model of restenosis is technically challenging. In this protocol we show the key technical details essential for successfully performing wire injury to induce consistent&#160;neointima for studies of restenosis.

Un modelo murino de restenosis arterial: Aspectos Técnicos del femoral Lesiones alambre

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to ...

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 ...

Transthoracic Echocardiographic Examination in the Rabbit Model

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Here we describe, step by step, a detailed protocol for performing echocardiography in the rabbit model. We show how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Examen Ecocardiográfico Transtorácico en el Modelo Conejo

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to ...

A Rabbit Venous Interposition Model Mimicking Revascularization Surgery using Vein Grafts to Assess Intimal Hyperplasia under Arterial Blood Pressure

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor because of the acceleration of intimal hyperplasia due to the exposure to arterial blood pressure. The present protocol is designed for the establishment of experimental venous intimal hyperplasia by interposing rabbit jugular veins to the ipsilateral carotid arteries. The protocol does not require surgical procedures deep in the body trunk and the extent of the incision is limited, which is less invasive for the animals, allowing long-term observation after implantation. This simple procedure enables researchers to investigate strategies to attenuate the progression of intimal hyperplasia of the implanted vein grafts. Using this protocol, we reported the effects transduction of microRNA-145 (miR-145), which is known to control the phenotype of vascular smooth muscle cells (VSMCs) from the proliferative to the contractile state, into harvested vein grafts. We confirmed the attenuation of intimal hyperplasia of vein grafts by transducing miR-145 before implantation surgery through the phenotype change of the VSMCs. Here we report a less invasive experimental platform to investigate the strategies that can be used to attenuate intimal hyperplasia of vein grafts in revascularization surgeries.

The present protocol aims to experimentally create venous intimal hyperplasia by subjecting veins to arterial blood pressure for developing strategies to attenuate venous intimal hyperplasia following revascularization surgery using vein grafts.

Un modelo de interposición venosa de conejo imitando la cirugía de revascularización usando injertos de vena para evaluar la hiperplasia intimal bajo presión arterial arterial

Although vein grafts have been commonly used as autologous grafts in revascularization surgeries for ischemic diseases, the long-term patency remains poor ...

Creation of Two Saccular Elastase-Digested Aneurysms with Different Hemodynamics in One Rabbit

Preclinical animal models with hemodynamic, morphologic, and histologic characteristics close to human intracranial aneurysms play a key role in the understanding of the pathophysiological processes and the development and testing of new therapeutic strategies. This study aims to describe a new rabbit aneurysm model that allows the creation of two elastase-digested saccular aneurysms with different hemodynamic conditions within the same animal.
Five female New Zealand white rabbits with a mean weight of 4.0 (&#177; 0.3) kg and mean age of 25 (&#177;5) weeks underwent microsurgical stump and bifurcation aneurysm creation. One aneurysm (stump) was created by right common carotid artery (CCA) exposure at its origin at the brachiocephalic trunk. A temporary clip was applied at the CCA origin and another, 2 cm above. This segment was treated with a local injection of 100 U of elastase for 20 min. A second aneurysm (bifurcation) was created by suturing an elastase-treated arterial pouch into the end-to-side anastomosis of the right CCA to left CCA. Patency was controlled by fluorescence angiography immediately after creation.
The average duration of surgery was 221 min. The creation of two aneurysms in the same animal was successful in all rabbits without complication. All aneurysms were patent immediately after surgery except for one bifurcation aneurysm, which showed an extreme tissue reaction due to elastase incubation and an immediate intraluminal thrombosis. No mortality was observed during surgery and up to one-month follow-up. Morbidity was limited to a transient vestibular syndrome (one rabbit), which recovered spontaneously within one day.
Demonstrated here for the first time is the feasibility of creating a two-aneurysm rabbit model with stump and bifurcation hemodynamic characteristics and highly degenerated wall conditions. This model allows the study of the natural course and potential treatment strategies on the basis of aneurysm biology under different flow conditions.

This protocol describes the steps for the creation of a rabbit model with two elastase-digested aneurysms with different hemodynamics (stump and bifurcation constellation). This allows the testing of novel endovascular devices in aneurysms with different angioarchitecture and hemodynamic conditions within a single animal.

Creación de dos aneurismas digeridos por elastasa sacular con diferente hemodinámica en un conejo

Preclinical animal models with hemodynamic, morphologic, and histologic characteristics close to human intracranial aneurysms play a key role in the ...

Isolated Lung Perfusion System in the Rabbit Model

The isolated lung perfusion system has been widely used in pulmonary research, contributing to elucidate the lungs&#39; inner workings, both micro and macroscopically. This technique is useful in the characterization of pulmonary physiology and pathology by measuring metabolic activities and respiratory functions, including interactions between circulatory substances and the effects of inhaled or perfused substances, as in drug testing. While in vitro methods involve the slicing and culturing of tissues, the isolated ex vivo lung perfusion system allows to work with a complete functional organ making possible the study of a continuous physiological function while recreating ventilation and perfusion. However, it should be noted that the effects of the absence of central innervation and lymphatic drainage still have to be fully assessed. This protocol aims to describe the assembly of the isolated lung apparatus, followed by the surgical extraction and cannulation of lungs and heart from experimental lab animals, as well as to display the perfusion technique and signal processing of data. The average viability of the isolated lung ranges between 5-8 h; during this period, the pulmonary capillary permeability increases, causing edema and lung injury. The functionality of preserved pulmonary tissue is measured by the capillary filtration coefficient (Kfc), used to determine the extent of pulmonary edema through time.

The isolated rabbit lung preparation is a gold standard tool in pulmonary research. This publication aims to describe the technique as developed for the study of physiological and pathological mechanisms involved in airway reactivity, lung preservation, and preclinical research in lung transplantation and pulmonary edema.

Sistema de perfusión pulmonar aislada en el modelo de conejo

The isolated lung perfusion system has been widely used in pulmonary research, contributing to elucidate the lungs&#39; inner workings, both micro and ...

A Rabbit Aortic Valve Stenosis Model Induced by Direct Balloon Injury

Animal models are emerging as an important tool to understand the pathologic mechanisms underlying aortic valve stenosis (AVS) because of the lack of access to reliable sources of diseased human aortic valves. Among the various animal models, AVS rabbit models are one of the most commonly used in large animal studies. However, traditional AVS rabbit models require a long-term period of dietary supplementation and genetic manipulation to induce significant stenosis in the aortic valve, limiting their use in experimental studies. To address these limitations, a new AVS rabbit model is proposed, in which stenosis is induced by a direct balloon injury to the aortic valve. The present protocol describes a successful technique for inducing AVS in New Zealand white (NZW) rabbits, with step-by-step procedures for the preparation, the surgical procedure, and the post-operative care. This simple and reproducible model offers a promising approach for studying the initiation and progression of AVS and provides a valuable tool for investigating the underlying pathological mechanisms of the disease.

An appropriate animal model is needed to understand the pathologic mechanisms underlying aortic valve stenosis (AVS) and to evaluate the efficacy of therapeutic interventions. The present protocol describes a new procedure for developing the AVS rabbit model via a direct balloon injury in vivo.

Un modelo de estenosis valvular aórtica de conejo inducida por lesión directa con balón

Animal models are emerging as an important tool to understand the pathologic mechanisms underlying aortic valve stenosis (AVS) because of the lack of ...