1. Texto protocolo <ol><li> Antes de prosseguir para a cirurgia, anestesiar um rato macho (C57BL / 6), que é de 6 semanas de idade ou mais velhos por inalação de 2-5% de isoflurano. Realizar uma pitada de igual para confirmar que o animal é suficientemente anestesiados. </li><li> O rato inconsciente é colocado de costas sobre uma almofada quente para manter uma temperatura constante de 37 ° C. O peito precordial no lado esquerdo é raspada. </li><li> Fixe o mouse para um dispositivo de intubação com uma câmara de isoflurano-cheia. Insira uma sonda de 0,2 de diâmetro interno para dentro da traqueia do rato através da boca, em seguida, colocar o rato intubado numa área asséptica cirúrgica (37 ° C por um controlador de temperatura) e ligar o tubo endotraqueal a um ventilador (taxa de 120 por minuto, a pressão de 4-6 mmH 2 O); desinfectar a área com betadine e etanol a 75%. </li><li> Aplicar pomada oftálmica para os olhos do rato. Coloque eletrodos padrão ECG nas patas e conecte o mouse para o gravador de ECG. </li&gt; <li> Use tesoura estéril para fazer uma incisão de 1,5 cm ao longo da linha axilar média. Tesoura são usados ​​em vez de um bisturi para evitar lesões no tecido subjacente, em ratos. Em seguida, use uma tesoura sem corte-ponta dos vasos de dissecar e retirar o músculo precordial da parede torácica. </li><li> Realizar uma toracotomia esquerda entre a terceira ea quarta costelas para visualizar a superfície anterior do coração e do pulmão esquerdo </li><li> Além disso retrair a parede torácica, utilizando um retractor adequado, a fim de melhorar a visualização e a acessibilidade. Retire o pericárdio, usando uma pinça dentada e atraumáticas tesouras. </li><li> Ligar a artéria coronária esquerda, colocando a agulha (ligada com fio de sutura 7-0 Ethilon) sob a artéria com uma banda de miocárdio entre a ligadura e a artéria. A oclusão da artéria coronária bem sucedida é verificada por hipocinesia / acinesia da parede ventricular anterior esquerda e pelas alterações de gravação de ECG (por exemplo, a elevação do segmento ST, QRS broadening) </li><li> Feche o peito, colocando dois pontos (6-0 Ethilon) nas costelas terceiro e quarto lugares. </li><li> Use 5-0 Ethilon para fechar a pele. </li><li> Para analgesia pós-operatória, administrar uma única injecção intraperitoneal de buprenorfina (0,05 mg / kg). Os animais se recupera espontaneamente dentro de 2-5 minutos depois de parar anestesia isoflurano. Por fim, colocar o rato em uma gaiola quente e proporcionar 0,6 mg / ml de buprenorfina na água de beber (sobreposição de texto: 0,6 mg / ml em água de beber), para evitar desconforto pós-operatório. Acompanhar de perto o mouse para as primeiras 24 horas após a cirurgia. </li><li> Ecocardiografia é realizada para avaliar a função cardíaca de 3 dias após infarto do miocárdio. Sucesso do procedimento é verificado por acinesia na parede ventricular anterior esquerda (veja o vídeo em anexo nos Resultados). No final da experiência, o coração irá ser recolhido e armazenado em-80oC para posteriores investigações. Expressão de genes ie. </li></ol>

<ol>
	<li>Tabrizchi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beta-blocker+therapy+after+acute+myocardial+infarction.">Beta-blocker therapy after acute myocardial infarction.</a> Expert Rev. Cardiovasc. Ther. 11, 293-296 (2013).</li><li>Pell, S., Fayerweather, W. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trends+in+the+incidence+of+myocardial+infarction+and+in+associated+mortality+and+morbidity+in+a+large+employed+population,+1957-1983.">Trends in the incidence of myocardial infarction and in associated mortality and morbidity in a large employed population, 1957-1983.</a> N. Engl. J. Med. 312, 1005-1011 (1985).</li><li>Ramunddal, T., Gizurarson, S., Lorentzon, M., Omerovic, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiarrhythmic+effects+of+growth+hormone--in+vivo+evidence+from+small-animal+models+of+acute+myocardial+infarction+and+invasive+electrophysiology.">Antiarrhythmic effects of growth hormone--in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology.</a> J. Electrocardiol. 41, 144-151 (2008).</li><li>Thom, T., Haase, N., Rosamond, W., Howard, V. J., Rumsfeld, J., Manolio, T., Zheng, Z. J., Flegal, K., O'Donnell, C., Kittner, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heart+disease+and+stroke+statistics--2006+update:+A+report+from+the+american+heart+association+statistics+committee+and+stroke+statistics+subcommittee.">Heart disease and stroke statistics--2006 update: A report from the american heart association statistics committee and stroke statistics subcommittee.</a> Circulation. 113, 85-151 (2006).</li><li>van den Bos, E. J., Mees, B. M., de Waard, M. C., de Crom, R., Duncker, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+model+of+cryoinjury-induced+myocardial+infarction+in+the+mouse:+A+comparison+with+coronary+artery+ligation.">A novel model of cryoinjury-induced myocardial infarction in the mouse: A comparison with coronary artery ligation.</a> Am. J. Physiol. Heart Circ. Physiol. 289, 1291-1300 (2005).</li><li>Omerovic, E., Ramunddal, T., Lorentzon, M., Nordlander, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+neuropeptide+y2+receptor+blockade+on+ventricular+arrhythmias+in+rats+with+acute+myocardial+infarction.">Effects of neuropeptide y2 receptor blockade on ventricular arrhythmias in rats with acute myocardial infarction.</a> Eur. J. Pharmacol. 565, 138-143 (2007).</li><li>Ahn, D., Cheng, L., Moon, C., Spurgeon, H., Lakatta, E. G., Talan, M. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Induction+of+myocardial+infarcts+of+a+predictable+size+and+location+by+branch+pattern+probability-assisted+coronary+ligation+in+c57bl/6+mice.">Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in c57bl/6 mice.</a> Am. J. Physiol. Heart Circ. Physiol. 286, 1201-1207 (2004).</li><li>Lindbom, M., Ramunddal, T., Camejo, G., Waagstein, F., Omerovic, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+effects+of+myocardial+creatine+depletion+on+left+ventricular+function+morphology+and+lipid+metabolism:+Study+in+a+mouse+model.">In vivo effects of myocardial creatine depletion on left ventricular function morphology and lipid metabolism: Study in a mouse model.</a> J. Card Fail. 14, 161-166 (2008).</li><li>Omerovic, E., Bollano, E., Basetti, M., Kujacic, V., Waagstein, L., Hjalmarson, A., Waagstein, F., Soussi, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bioenergetic,+functional+and+morphological+consequences+of+postinfarct+cardiac+remodeling+in+the+rat.">Bioenergetic, functional and morphological consequences of postinfarct cardiac remodeling in the rat.</a> J. Mol. Cell. Cardiol. 31, 1685-1695 (1999).</li><li>Gao, E., Lei, Y. H., Shang, X., Huang, Z. M., Zuo, L., Boucher, M., Fan, Q., Chuprun, J. K., Ma, X. L., Koch, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+and+efficient+model+of+coronary+artery+ligation+and+myocardial+infarction+in+the+mouse.">A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse.</a> Circ. Res. 107, 1445-1453 (2010).</li></ol>

Não há conflitos de interesse declarados.

O procedimento cirúrgico de laqueadura LCA, como demonstrado neste relatório é um método confiável e reprodutível para a indução de infarto do miocárdio experimental em ratos 3, 6. A ligadura da ACE de acordo com este protocolo induz isquemia miocárdica envolvendo tipicamente ~ 40% do ventrículo esquerdo 3. Isso induz alterações significativas de ECG do segmento ST 7 e palidez visível na superfície anterior do coração. Devido ao enfarte do miocárdio grande, a mortalidad...

modified technique for coronary artery ligation in mice

Enfarte do miocárdio (MI) é uma das mais importantes causas de mortalidade em humanos 1-3. A fim de melhorar a morbidade e mortalidade em pacientes com MI precisamos de melhor conhecimento sobre a fisiopatologia da isquemia miocárdica. Esse conhecimento pode ser útil para definir novos alvos terapêuticos para inovadoras terapias cardiovasculares 4. Modelo MI experimental em camundongos é um modelo cada vez mais popular de pequenos animais em pesquisa pré-clínica em que MI é induzida por meio de ligadura permanente ou temporária da artéria coronária esquerda (ACE) 5. Neste vídeo, descrevemos o método passo-a-passo de como induzir MI experimental em ratos. O animal é primeiro anestesiadas com isoflurano a 2%. O rato inconsciente é então intubados e conectados a um ventilador para a ventilação artificial. O lado esquerdo do peito é raspada e de 1,5 cm ao longo da incisão média axilar linha é feita na pele. O músculo peitoral maior esquerdo é sem rodeios dissociated até que as nervuras se encontram expostos. As camadas musculares são puxados para o lado e fixadas com um retractor de pálpebras. Após estas preparações, toracotomia esquerda é realizada entre as costelas, terceiro e quarto, a fim de visualizar a superfície anterior do coração e do pulmão esquerdo. O segmento proximal da artéria LCA é então ligado com um fio de sutura 7-0 Ethilon que normalmente induz uma dimensão do enfarte ~ 40% do ventrículo esquerdo. No final, a caixa é fechada e os animais recebem analgesia pós-operatória (Temgesic, 0,3 mg/50 ml, ip). Os animais são mantidos numa gaiola quente até recuperação espontânea.

<html><table border="1" ><tbody><tr><td> Instrumento </td><td> Descrição da função </td></tr><tr><td> Blunt-ponta tesoura </td><td> Usado para cortar a pele, músculo peitoral intercostal, e suturas </td></tr><tr><td> Retrator olho </td><td> Usado para expor vista cirúrgico </td></tr><tr><td> Blunt-ponta fórceps </td><td> Usados ​​para agarrar a pele eo músculo </td></tr><tr><td> Suporte da agulha </td><td> Para segurar uma agulha </td></tr><tr><td> 5-0 </td><td> Utilizados para a sutura da pele </td...

Watch this Scientific Journal Video about Modified Technique for Coronary Artery Ligation in Mice at JoVE.com

Modified Technique for Coronary Artery Ligation in Mice

O procedimento cirúrgico utilizado para induzir o enfarte do miocárdio experimental em ratos começa com toracotomia esquerda entre a terceira e quarta das nervuras, a fim de visualizar a superfície anterior do coração e do pulmão esquerdo. A artéria coronária esquerda é ligada, a caixa é fechada e o rato é deixado a recuperar-se espontaneamente.

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 ...

modified-technique-for-coronary-artery-ligation-in-mice

Research

JoVE Journal

Medicine

25.3K visualizações.  Sahlgrenska Academy, University of Gothenburg. O procedimento cirúrgico utilizado para induzir o enfarte do miocárdio experimental em ratos começa com toracotomia esquerda entre a terceira e quarta das nervuras, a fim de visualizar a superfície anterior do coração e do pulmão esquerdo. A artéria coronária esquerda é ligada, a caixa é fechada e o rato é deixado a recuperar-se espontaneamente.

Vídeo: Modified Technique for Coronary Artery Ligation in Mice

Use of a Hanging Weight System for Coronary Artery Occlusion in Mice

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available 1-38. Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of knockout mouse studies is particularly important 7, 14, 30, 39. Despite the fact that previous studies have already successfully performed cardiac ischemia and reperfusion in mice, this model is technically very challenging. Particularly, visual identification of the coronary artery, placement of the suture around the vessel and coronary occlusion by tying off the vessel with a supported knot is technically difficult. In addition, re-opening the knot for intermittent reperfusion of the coronary artery during IP without causing surgical trauma adds additional challenge. Moreover, if the knot is not tied down strong enough, inadvertent reperfusion due to imperfect occlusion of the coronary may affect the results. In fact, this can easily occur due to the movement of the beating heart.
Based on potential problems associated with using a knotted coronary occlusion system, we adopted a previously published model of chronic cardiomyopathy based on a hanging weight system for intermittent coronary artery occlusion during IP 39. In fact, coronary artery occlusion can thus be achieved without having to occlude the coronary by a knot. Moreover, reperfusion of the vessel can be easily achieved by supporting the hanging weights which are in a remote localization from cardiac tissues.
We tested this system systematically, including variation of ischemia and reperfusion times, preconditioning regiments, body temperature and genetic backgrounds39. In addition to infarct staining, we tested cardiac troponin I (cTnI)
as a marker of myocardial infarction in this model. In fact, plasma levels of cTnI correlated with infarct sizes (R2=0.8). Finally, we could show in several studies that this technique yields highly reproducible infarct sizes during murine IP and myocardial infarction6, 8, 30, 40, 41. Therefore, this technique may be helpful for researchers who pursue molecular mechanisms involved in cardioprotection by IP using a genetic approach in mice with targeted gene deletion. Further studies on cardiac IP using transgenic mice may consider this technique.

A murine model for myocardial ischemia and ischemic preconditioning is an important tool study cardioprotective mechanisms in vivo. Here, we report an easy applicable in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion.

Uso de um Sistema de Peso de suspensão para oclusão da artéria coronária em ratos

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available 1-38. ...

Medicina

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 ...

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

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 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 failure.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. 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. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. 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 reperfusion. In contrast, the infarct area at 24 hr 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.
Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.

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 ...

Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. 
During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). 
The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. 
The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.

Coronary flow reserve (CFR) is useful for assessment of myocardial oxygen demand and evaluation of cardiovascular risk. This study establishes a step-by-step transthoracic Doppler echocardiographic (TTDE) method for longitudinal monitoring of the changes in CFR, as measured from coronary artery in mice, under the experimental pressure overload of aortic banding.

Avaliação ultra-som base de Artéria Coronária Flow e Fluxo Coronariano Reserve Usando o modelo de sobrecarga de pressão no Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow ...

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 ...

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 ...

Left Coronary Artery Ligation: A Surgical Murine Model of Myocardial Infarction

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In order to explore the pathophysiological changes after myocardial infarction and design future treatments, research models of MI are required. Permanent ligation of the left coronary artery (LCA) in mice is a popular model to investigate cardiac function and ventricular remodeling post MI. Here we describe a less invasive, reliable, and reproducible surgical murine MI model by permanent ligation of the LCA. Our surgical model comprises of an easily reversible general anesthesia, endotracheal intubation that does not require a tracheotomy, and a thoracotomy. Electrocardiography and troponin measurement should be performed to ensure MI. Echocardiography at day 28 after MI will discern heart function and heart failure parameters. The degree of cardiac fibrosis can be evaluated by Masson's trichrome staining and cardiac MRI. This MI model is useful for studying the pathophysiological and immunological alterations after MI.

Presented here is a surgical procedure for permanent ligation of the left coronary artery in mice. This model can be used to investigate the pathophysiology and associated inflammatory response after myocardial infarction.

Laqueadura da Artéria Coronária Esquerda: Um Modelo Murino Cirúrgico de Infarto do Miocárdio

Ischemic heart disease and subsequent myocardial infarction (MI) is one of the leading causes of mortality in the United States and around the world. In ...

Left Anterior Descending Coronary Artery Ligation for Ischemia-Reperfusion Research: Model Improvement via Technical Modifications and Quality Control

Coronary heart disease is the leading cause of death globally. Complete cessation of blood flow in coronary arteries causes ST-segment elevation myocardial infarction (STEMI), resulting in cardiogenic shock and fatal arrhythmia, which are associated with high mortality. Primary coronary intervention (PCI) for recanalizing the coronary artery significantly improves the outcomes of STEMI, but advancements made in shortening the door-to-balloon time have failed to reduce in-hospital mortality, suggesting that additional therapeutic strategies are required. Left anterior descending coronary artery (LAD) ligation in rats is an animal model for acute myocardial IR research that is comparable to the clinical scenario in which rapid coronary recanalization through PCI is used for STEMI; however, PCI-induced STEMI is a technically challenging and complicated operation associated with high mortality and great variation in infarction size. We identified the ideal position for LAD ligation, created a gadget to control a snare loop, and supported a modified surgical maneuver, thereby reducing tissue damage, to establish a reliable and reproducible acute myocardial ischemia-reperfusion (IR) research protocol for rats. This is a non-survival surgery. We also propose a method for validating the quality of study results, which is a critical step for determining the accuracy of subsequent biochemical analyses.

Herein, we present a protocol focusing on the quality control of the left anterior descending coronary artery ligation by technically modifying the traditional procedure in rats for acute myocardial ischemia-reperfusion research.

Ligadura da Artéria Coronária Descendente Anterior para Pesquisa de Isquemia-Reperfusão: Aprimoramento do Modelo via Modificações Técnicas e Controle de Qualidade