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

NOTA: Todos os procedimentos experimentais descritos nesta seção foram aprovados pelo Animal Care and Research Comité Consultivo da Katholieke Universiteit Leuven Institucional (Project: 154/2013-B De Geest). 1. A ligação permanente da artéria coronária descendente anterior esquerda <ol><li> Anestesiar o rato por administração intraperitoneal de 40 mg / kg a 70 mg / kg de pentobarbital de sódio. Verifique se o mouse atinge o seu bom plano de anestesia quando já não reage uma pitada dedo do pé firme. Sempre confirme anesthetization adequada dessa forma antes de qualquer procedimento cirúrgico ou intervenção. Use lubrificante pomada oftálmica para prevenir o ressecamento da córnea, enquanto sob anestesia. Proporcionar analgesia pré-operatória 2-4 h antes do início do procedimento (buprenorfina 0,05 mg / kg SQ). <ol><li> Aplicar técnicas de assepsia consistentes durante a cirurgia sobrevivência. Implementar procedimentos que inibem a um máximo possível extensão con microbianacontaminação por isso que a infecção significativa ou supuração não ocorre. Estes procedimentos incluem a utilização de instrumentos esterilizados e materiais estéreis, desinfecção da área cirúrgica, e remoção de pele / cabelo sobre o local da cirurgia e desinfecção deste site. </li></ol></li><li> Intubate do mouse com um embotado agulha de calibre 20 auto-preparado. <ol><li> Coloque o mouse em decúbito dorsal, com hiperextensão da cabeça. <ol><li> Focalizar a luz na região do pescoço. Levante a língua com uma pincet embotada. A entrada da laringe pode ser claramente visto. </li><li> Passe a agulha embotada pela laringe na traqueia sob visão direta. Avaliar intubação correta ligando o mouse para o ventilador (volume AVC em ul: 3 x peso corporal (g) + 155; frequência: 120 batidas por minuto). </li></ol></li><li> Alternativamente, melhorar a visualização de entubação endotraqueal, expondo primeiro cuidadosamente a traquéia. <ol><li> Faça um 5 milímetros incisão mid-neck e retrairtecido muscular, um pouco acima da traqueia. </li><li> Realize a intubação usando um microscópio estereoscópico cirúrgico para a visualização direta da traquéia. Levante a língua e entrar na agulha de calibre 20 auto-preparado embotados na traquéia. Confirme intubação correta ligando o mouse para o ventilador (volume AVC em ul: 3 x peso corporal (g) + 155; frequência: 120 batidas por minuto). </li></ol></li></ol></li><li> Mantenha o mouse na posição supina e corrigir o mouse com fita adesiva. Realizar a cirurgia em uma almofada de aquecimento para evitar a hipotermia. <ol><li> Raspar e desinfectar a pele com Betadine. Tome cuidado para que o membro posterior esquerdo cruza o membro posterior direito, a fim de obter uma melhor visão sobre o ventrículo esquerdo durante a cirurgia. </li></ol></li><li> Fazer uma pequena incisão cutânea transversal acima do esterno e separar a pele e os músculos subjacentes. </li><li> Puxe de lado a m. peitoral menor e m. peitoral maior com uma sutura 5-0 seda. </li><li> Faça um incision no terceiro espaço intercostal por inserção de um pincet embotada. </li><li> Mova o pincet sob os músculos intercostais de lateral para medial até o esterno é atingido. Perfurar a parede torácica, empurrando o pincet a partir do interior para a pele. Complete a toracotomia com cuidado cortando o músculo intercostal pouco acima do pincet com uma pequena tesoura. Utilizar esta técnica para prevenir puncionamento dos pulmões. </li><li> Coloque uma esponja imersos em NaCl a 0,9% na cavidade, para proteger os pulmões. Introduzir um espalhador de ferida (afastador peito) para o espaço intercostal para obter uma exposição do lado esquerdo do coração. A partir de agora, o átrio esquerdo, o ventrículo esquerdo, e descendente anterior esquerda da artéria coronária são visíveis ao microscópio estereoscópico. </li><li> Realize uma ligadura da artéria descendente anterior coronária com um único ligadura 6-0 prolene cerca de 1 mm sob a ponta do átrio esquerdo. Isto é distal a partir do primeiro ramo diagonal. NOTA: Como alternativa, 7-0 (00,05 milímetros de diâmetro) ou 8-0 segmentos (0,04 mm de diâmetro) podem ser utilizados. A agulha é um círculo Taper agulha Ponto C-1 13 milímetros 3/8. Ligação bem sucedida da artéria coronária descendente anterior da artéria coronária induz descoloração imediata, resultando em um miocárdio pálido aparecendo no território afectado. </li><li> Remova o espalhador de ferida (afastador no peito). <ol><li> Coloque três 6-0 Ti-Cron em torno do espaço intercostal. Antes de apertar as suturas, remova a esponja da cavidade torácica e re-expandir os pulmões, bloqueando a saída do ventilador. Ao fazer isso, os pulmões se reconectar com a pleura parietal. </li><li> Posteriormente, puxe os fios para suturas apertado e repetir re-expansão, pressionando para baixo no peito. Confirmar o encerramento bem sucedido do tórax usando uma pequena quantidade de solução salina (sem bolhas de ar deve ser visto quando se aplica pressão sobre o peito). </li><li> Olhe através do músculo intercostal para confirmar expansão normal dos pulmões. Reposicionar ambos os músculos peitorais, servindo como umbarreira adicional para a prevenção de um pneumotórax. </li></ol></li><li> Feche a pele com 5-0 silk-suturas. </li><li> Desconecte o mouse do ventilador e permitir a recuperação na almofada de aquecimento. Não deixe um animal sem supervisão até que ele recuperou a consciência suficiente para manter decúbito esternal. Não devolva um animal que passou por uma cirurgia para a companhia de outros animais até que esteja totalmente recuperado. </li><li> Consistentemente fornecer analgesia pós-operatória (buprenorfina 0,05 mg / kg SQ BID por pelo menos 48 horas após a cirurgia). </li></ol> 2. as medidas in vivo hemodinâmica invasiva em camundongos <ol><li> Antes do procedimento, submergir o cateter Millar 1.0 French pressão em água estéril a 37 ° C durante pelo menos 30 minutos para minimizar a variação de sinal. Eletronicamente calibrar o sensor de pressão a 0 mm Hg e 100 mm Hg e gravar dados a 2.000 Hz. </li><li> Realizar a anestesia por administração intraperitoneal de 1,4 g / kg de uretano. Verifique seo mouse atinge o seu bom plano de anestesia quando já não reage uma pitada dedo do pé firme. </li><li> Posicione o mouse anestesiados em decúbito dorsal. Fixe seus membros com fita adesiva. Manter a temperatura corporal com uma almofada de aquecimento e acompanhar com uma sonda retal. Raspar a região do pescoço e fazer uma incisão na linha média na região do pescoço para expor a glândula tireóide. </li><li> Fixar o pescoço com agulhas tortas. </li><li> Puxe de lado a glândula salivar e expor a artéria carótida comum direita. O nervo vago, que se assemelha a um fio branco, encontra-se ao longo da artéria. Separe cuidadosamente a artéria carótida do nervo vago com pinça curvas. </li><li> Passar uma pinça curva sob a artéria carótida comum direita para separá-lo de outros tecidos. Remover o tecido conjuntivo em torno da artéria. </li><li> Passe dois fios de seda 6-0 sob a artéria carótida comum direita. Faça um nó apertado no fio top, que é colocado na direção da cabeça, fechar e fixar com um kocher (ligadura oclusiva distal). Passar a proxifio mal duas vezes da esquerda para a direita e fixar com 2 kochers (fio não oclusivo proximal). </li><li> Manter a artéria carótida húmido soltando estéril 0,9% de NaCl. Seque o excesso de líquido com cotonetes. </li><li> Realizar uma incisão na artéria carótida comum direita com uma agulha de calibre 26 entre a ligadura distal e o fio não oclusivo proximal. </li><li> Introduzir o sensor de pressão no interior da artéria. Verificar que não há perda de sangue. Empurrar suavemente o cateter de pressão Francesa Millar 1.0 para a frente e ajustar o fio não oclusivo proximal de tal modo que o cateter pode passar cuidadosamente através do fio sob a clavícula. <ol><li> Minimizar a perda de sangue durante o ajuste do fio não oclusivo proximal. Não comprimir o sensor de pressão demasiada ao avançar, uma vez que é muito frágil. Desde o fio proximal não deve obstruir a artéria, o navio deve permanecer cheia de sangue. </li></ol></li><li> Comece a gravar o sinal de pressão. Um sinal de pressão arterial Fluctuates em um rato saudável entre a pressão diastólica de 60-70 mmHg e uma pressão sistólica de 100-120 mm Hg. </li><li> Direcionar o cateter através da artéria inominada e através da aorta para o ventrículo esquerdo. A pressão ventricular oscila entre 0 mmHg e 100-120 mm Hg. Permitir que o cateter para estabilizar no interior do ventrículo esquerdo. Registar o sinal durante 30 min a 60 min, dependendo dos requisitos experimentais. </li><li> Após a conclusão da experiência, embeber o cateter em Alconox 1% durante 30 min. Lavar o cateter com água Milli-Q. Guarde o cateter em um bloco de espuma. </li><li> Recuperar dados do software de gravação, para posterior análise. <ol><li> Para a análise dos dados, considere um intervalo de tempo em que o sinal de pressão é estável. Escolha pelo menos 10 ciclos cardíacos consecutivos de os dados gravados de interesse. </li><li> Use software LabChart versão 8.0 ou similar para analisar a freqüência cardíaca, a pressão sistólica ventricular esquerda máxima, o Ventr esquerda diastólica mínimapressão icular, a taxa de pico de contração isovolumétrica ventricular esquerda (dP / dt max), a taxa de pico de relaxamento isovolumétrica ventricular esquerda (dP / dt min), a pressão ventricular esquerda diastólica final, e a constante de tempo do isovolumétrica ventricular esquerda queda de pressão (tau) 7. NOTA: A pressão diastólica final corresponde à pressão no ponto de tempo imediatamente antes do aumento súbito de pressão induzida pela contração isovolumétrica. O cálculo de tau é baseada no ajustamento da pressão do ventrículo esquerdo para uma curva de decaimento monoexponencial, expressa como P (t) = P 0 e -t / tau + b, Nesta fórmula, P (t) é a pressão ventricular esquerda em vez t depois que o valor negativo máximo de dP / dt foi atingido. O parâmetro b correspondente à assimptota teórico, em que uma abordagem simplificada pode ser assumido como sendo zero. Relaxamento isovolumétrico aprimorada resulta em um valor menor do tau. </li></ol></li></ol&gt;

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None of the authors reports competing financial interests.

Alterações crônicas na estrutura e função do miocárdio, o desenvolvimento de disfunção ventricular esquerda, e progressão para insuficiência cardíaca pode ser investigado em vários modelos de murino 12. A remodelação cardíaca e disfunção pode ser induzida pela lesão do miocárdio ou por pressão sobrecarregar secundário para transversal constrição da aorta, ou podem ser investigados em modelos genéticos de cardiomiopatia dilatada 12. Obviamente, o benefício mais pronunciado d...

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

A insuficiência cardíaca é uma síndrome em que o coração não consegue bombear o sangue a uma taxa proporcional aos requisitos celulares de oxigênio em repouso ou durante o estresse. É caracterizada pela retenção de líquidos, falta de ar e fadiga, em particular no esforço. A insuficiência cardíaca é um problema crescente de saúde pública, a principal causa de hospitalização, e uma das principais causas de mortalidade. Doença isquêmica do coração é a principal causa de insuficiência cardíaca. A remodelação ventricular refere-se a alterações na estrutura, tamanho e forma do ventrículo esquerdo. Esta remodelação arquitetônica do ventrículo esquerdo é induzida por lesão (por exemplo, infarto do miocárdio), por sobrecarga de pressão (por exemplo, hipertensão arterial sistêmica ou estenose aórtica), ou por sobrecarga de volume. Uma vez que a remodelação ventricular afecta o stress da parede, que tem um profundo impacto sobre a função cardíaca e no desenvolvimento de insuficiência cardíaca. Um modelo de ligadura permanente da descendin anterior esquerdag artéria coronária em ratos é usado para investigar o remodelamento ventricular e função cardíaca pós-infarto do miocárdio. Este modelo é fundamentalmente diferente, em termos de objetivos e relevância fisiopatológica em comparação com o modelo de ligadura transiente da artéria descendente anterior coronária. Neste último modelo de lesão de isquemia / reperfusão, o grau inicial do enfarte pode ser modulado por factores que afectam o salvamento do miocárdio após a reperfusão. Em contraste, a área de enfarte em 24 horas após a ligação permanente da artéria coronária descendente anterior da artéria coronária é fixo. A função cardíaca neste modelo será afetado por 1) o processo de expansão do infarto, a cura do infarto, e formação de cicatriz; e 2) o desenvolvimento concomitante de dilatação do ventrículo esquerdo, hipertrofia cardíaca, e remodelamento ventricular. Além do modelo de ligadura permanente da artéria coronária descendente anterior da artéria coronária, a técnica de mea hemodinâmica invasivame- em ratinhos é apresentado em pormenor.

A extensão do infarto do miocárdio pode ser avaliada por Evans azul / cloreto de 2,3,5-trifeniltetrazólio (TTC) dupla marcação. TTC é um indicador redox, o qual é convertido para vermelho escuro 1,3,5-triphenylformazan em tecidos, devido à actividade de várias desidrogenases, na presença de NADH 8 vivo. A Figura 1 mostra uma secção representativa do coração às 24 h após ligadura da artéria descendente anterior coronária. As áreas azuis manchados de indicar regiões não-isq...

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.

A ligação permanente da artéria coronária descendente anterior esquerda em Ratos: Um Modelo de Remodelação pós-infarto do miocárdio e insuficiência cardíaca

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

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27.5K visualizações.  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.

Vídeo: 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 da artéria coronária e injeção intramiocárdica em um 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 ...

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.

A aplicação de ligadura da artéria Cerebral Média Permanente no 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 ...

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 ligação da artéria coronária em ratos

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.

Um modelo murino de isquemia-reperfusão, através da ligadura da artéria Descendente Anterior Esquerda

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 Esquerda (LAD) ligação da artéria coronária: um modelo melhorado e simplificado para Infarto do Miocárdio

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.

Re-implantação direta de Esquerda da Artéria Coronária para a aorta em adultos com Origem Anômala da Coronária Esquerda da Artéria da artéria 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 do miocárdio murino usando ligadura permanente da artéria coronária descendente anterior esquerda

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.

Estabelecendo um modelo suíno de insuficiência cardíaca pós-miocárdio para tratamento de células-tronco

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.

Insuficiência cardíaca pós-miocárdio em oclusão coronariana de peito fechado/modelo de reperfusão em Miniporcos de Göttingen e Poros 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.

Geração e Caracterização do Infarto do Miocárdio Ventricular Direito Induzido pela Ligação Permanente da Artéria Coronária Direita em Camundongos

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