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

NOTA: Tutte le procedure sperimentali descritte in questa sezione sono stati approvati dalla cura degli animali e del Comitato consultivo di ricerca della Katholieke Universiteit Leuven istituzionale (Progetto: 154/2013-B De Geest). 1. permanente legatura dell&#39;arteria coronarica discendente anteriore sinistra <ol><li> Anestetizzare il mouse per somministrazione intraperitoneale di 40 mg / kg a 70 mg / kg di sodio pentobarbital. Assicurarsi che il mouse raggiunge il suo corretto piano di anestesia quando non reagisce più un pizzico punta ditta. Verificare sempre la corretta anestesia questo modo prima di qualsiasi procedura chirurgica o intervento. Utilizzare lubrificante pomata oftalmica per prevenire la secchezza della cornea mentre sotto anestesia. Fornire analgesia preoperatoria 2-4 ore prima dell&#39;inizio della procedura (buprenorfina 0,05 mg / kg SQ). <ol><li> Applicare tecniche asettiche coerenti durante l&#39;intervento chirurgico la sopravvivenza. Implementare procedure che inibiscono un con microbica massimo possibile misuracontaminazione in modo che l&#39;infezione significativo o suppurazione non si verifica. Queste procedure includono l&#39;uso di strumenti sterili e materiali sterili, disinfezione dell&#39;area chirurgica, e la rimozione di pelliccia / capelli sopra il sito chirurgico e la disinfezione di questo sito. </li></ol></li><li> Intubare il mouse con un smussato ago 20-gauge auto-preparata. <ol><li> Ponga il mouse in posizione supina con iperestensione del capo. <ol><li> Focalizzare la luce sulla regione del collo. Sollevare la lingua con un pincet smussata. L&#39;ingresso della laringe può essere visto chiaramente. </li><li> Passare l&#39;ago smussato attraverso la laringe nella trachea sotto visione diretta. Valutare corretta intubazione collegando il mouse per il ventilatore (stroke volume in microlitri: 3 x peso corporeo (g) + 155; Frequenza: 120 colpi al minuto). </li></ol></li><li> In alternativa, migliorare la visualizzazione di intubazione endotracheale esponendo con la massima attenzione la trachea. <ol><li> Fare un 5 millimetri un&#39;incisione mid-collo e ritrarretessuto muscolare appena sopra la trachea. </li><li> Eseguire l&#39;intubazione utilizzando uno stereomicroscopio chirurgica per la visualizzazione diretta della trachea. Sollevare la lingua e inserire la calibro 20 ago auto-preparata smussato nella trachea. Confermare corretta intubazione collegando il mouse per il ventilatore (stroke volume in microlitri: 3 x peso corporeo (g) + 155; Frequenza: 120 colpi al minuto). </li></ol></li></ol></li><li> Tenere il mouse in posizione supina e fissare il mouse con nastro. Eseguire un intervento chirurgico su una piastra elettrica per evitare l&#39;ipotermia. <ol><li> Shave e disinfettare la pelle con Betadine. Assicurarsi che l&#39;arto posteriore sinistra attraversa destra dell&#39;arto posteriore al fine di ottenere una migliore visualizzazione sul ventricolo sinistro durante l&#39;intervento chirurgico. </li></ol></li><li> Fai una piccola incisione cutanea trasversale fino allo sterno e separare la pelle ed i muscoli sottostanti. </li><li> Estrarre da parte la m. piccolo pettorale e m. pettorale con una sutura 5-0 seta. </li><li> Fai incision nel terzo spazio intercostale inserendo un pincet smussata. </li><li> Spostare il pincet sotto i muscoli intercostali da laterale a mediale fino a raggiungere lo sterno. Perforare la parete toracica spingendo la pincet dall&#39;interno alla pelle. Completare la toracotomia tagliando attentamente il muscolo intercostale appena sopra il pincet con una piccola forbice. Utilizzare questa tecnica per impedire punzonamento dei polmoni. </li><li> Mettere una spugna immersa in 0,9% NaCl nella cavità per proteggere i polmoni. Introdurre un spreader ferita (riavvolgitore petto) nello spazio intercostale per ottenere esposizione del lato sinistro del cuore. A partire da ora, l&#39;atrio sinistro, il ventricolo sinistro, e la discendente anteriore sinistra coronarica sono visibili con lo stereomicroscopio. </li><li> Eseguire una legatura della discendente anteriore dell&#39;arteria coronaria con un&#39;unica 6-0 prolene legatura di circa 1 mm sotto la punta dell&#39;atrio sinistro. Questo è distale dal primo ramo diagonale. NOTA: In alternativa, 7-0 (0Possono essere utilizzati .05 mm di diametro) o 8-0 fili (0,04 mm di diametro della). L&#39;ago è un cerchio Taper Point ago C-1 13 millimetri 3/8. Legatura successo della discendente anteriore dell&#39;arteria coronaria induce scolorimento immediata, risultando in un miocardio appare pallida nel territorio interessato. </li><li> Rimuovere la spreader ferita (divaricatore petto). <ol><li> Mettere tre 6-0 suture Ti-Cron intorno spazio intercostale. Prima di serrare le suture, rimuovere la spugna dalla cavità toracica e ri-expand polmoni bloccando il deflusso del ventilatore. In questo modo, i polmoni riconnettersi con la pleura parietale. </li><li> Successivamente, tirare le suture stretto e ripetere riespansione premendo sul petto. Conferma la chiusura successo del torace utilizzando una piccola quantità di soluzione salina (bolle d&#39;aria devono essere considerate quando si applica pressione sul torace). </li><li> Guardare attraverso il muscolo intercostale per confermare normale dilatazione dei polmoni. Riposizionare entrambi i muscoli pettorali, che serve come unulteriore ostacolo per la prevenzione di un pneumotorace. </li></ol></li><li> Chiudere la pelle con 5-0 seta-suture. </li><li> Scollegare il mouse dal ventilatore e consentire il recupero sulla piastra elettrica. Non lasciare un animale incustodito fino a quando non ha ripreso conoscenza sufficiente per mantenere decubito sternale. Non restituire un animale che ha subito un intervento chirurgico per la compagnia di altri animali fino alla completa guarigione. </li><li> Coerentemente fornire analgesia postoperatoria (buprenorfina 0,05 mg / kg SQ BID per almeno 48 ore dopo l&#39;intervento chirurgico). </li></ol> 2. In vivo Misure Invasive emodinamici nei topi <ol><li> Prima della procedura, immergere Francese Millar catetere pressione 1,0 in acqua sterile a 37 ° C per almeno 30 minuti per ridurre la deriva del segnale. Elettronicamente calibrare il sensore di pressione a 0 mmHg e 100 mmHg e registrare i dati a 2.000 Hz. </li><li> Eseguire anestesia mediante somministrazione intraperitoneale di 1,4 g / kg uretano. Controllare cheil mouse raggiunge il suo corretto piano di anestesia quando non reagisce più un pizzico punta ditta. </li><li> Posizionare il mouse anestetizzato in posizione supina. Fissare le sue membra con nastro adesivo. Mantenere la temperatura corporea con una piastra elettrica e monitorare con una sonda rettale. Shave regione del collo e fare una incisione mediana nella regione del collo per esporre la ghiandola tiroidea. </li><li> Fissare il collo con aghi piegati. </li><li> Estrarre da parte delle ghiandole salivari e esporre il diritto carotide comune. Il nervo vago, che assomiglia a un filo bianco, si trova lungo l&#39;arteria. Separare con cautela la carotide dal nervo vago con una pinza curva. </li><li> Passare una pinza curvo sotto il diritto carotide comune per separarla da altri tessuti. Rimuovere tessuto connettivo attorno l&#39;arteria. </li><li> Passare due 6-0 fili di seta sotto il diritto carotide comune. Fare un nodo stretto sul filo superiore, che si trova verso la testa, stretta, e fissare con un Kocher (occlusiva legatura distale). Passare il Proxifilo mal due volte da sinistra a destra e fissare con 2 Kochers (fili non occlusiva prossimale). </li><li> Mantenere la carotide umido facendo cadere sterile 0,9% NaCl. Asciugare il liquido in eccesso con bastoncini di cotone. </li><li> Fare un&#39;incisione nella giusta carotide comune con un ago calibro 26 tra la legatura distale e il filo non-occlusiva prossimale. </li><li> Introdurre il sensore di pressione nell&#39;arteria. Verificare che non vi è alcuna perdita di sangue. Spingere delicatamente Francese Millar catetere pressione 1.0 avanti e regolare il filo non-occlusiva prossimale in modo tale che il catetere può passare attentamente il cavo sotto la clavicola. <ol><li> Ridurre al minimo la perdita di sangue durante la regolazione del filo non occlusiva prossimale. Non comprimere il sensore di pressione troppo mentre avanza poiché è molto fragile. Poiché il filo prossimale non deve occludere l&#39;arteria, la nave deve rimanere pieno di sangue. </li></ol></li><li> Avviare la registrazione del segnale di pressione. Un segnale di pressione arteriosa Fluctuates in un sano mouse tra una pressione diastolica a 60 - 70 mmHg e una pressione sistolica di 100 - 120 mm Hg. </li><li> Dirigere il catetere attraverso l&#39;arteria anonima e tramite l&#39;aorta nel ventricolo sinistro. La pressione ventricolare oscilla tra 0 mm Hg e 100 - 120 mm Hg. Lasciare il catetere per stabilizzare all&#39;interno del ventricolo sinistro. Registrare il segnale per 30 min a 60 min a seconda delle esigenze sperimentali. </li><li> Dopo il completamento dell&#39;esperimento, immergere il catetere in Alconox 1% per 30 min. Lavare il catetere con acqua Milli-Q. Conservare il catetere in un blocco di schiuma. </li><li> Recuperare i dati del software di registrazione per ulteriori analisi. <ol><li> Per l&#39;analisi dei dati, si consideri un intervallo di tempo in cui il segnale di pressione è stabile. Scegli almeno 10 cicli cardiaci consecutivi dei dati registrati di interesse. </li><li> Utilizzare LabChart software versione 8.0 o simile per analizzare la frequenza cardiaca, la massima sistolica sinistra pressione ventricolare, il minimo ventr diastolica sinistraicular pressione, la velocità di picco di isovolumica contrazione ventricolare sinistra (dP / dt max), la velocità di picco di isovolumica rilassamento ventricolare sinistra (dP / dt min), la pressione ventricolare sinistra telediastolica, e la costante di tempo del ventricolo sinistro isovolumica caduta di pressione (tau) 7. NOTA: La pressione telediastolica corrisponde alla pressione al momento punto immediatamente prima l&#39;aumento della pressione indotta dalla contrazione isovolumica. Il calcolo di tau è basato sul montaggio della pressione ventricolare sinistra in una curva di decadimento monoesponenziale, espressa come P (t) = p 0 e -t / tau + b, In questa formula, P (t) è la pressione ventricolare sinistra al momento t dopo il valore negativo massimo di dP / dt è stato raggiunto. Il parametro b corrisponde al asintoto teorica, che in un approccio semplificato può essere assunto pari a zero. Maggiore relax isovolumica traduce in un valore più piccolo di tau. </li></ol></li></ol&gt;

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None of the authors reports competing financial interests.

Cambiamenti cronici nella struttura e funzione miocardica, lo sviluppo di disfunzione ventricolare sinistra, e la progressione di insufficienza cardiaca possono essere studiati in diversi modelli murini 12. Rimodellamento cardiaco e disfunzione può essere indotta da un danno miocardico o da pressioni sovraccaricare secondaria trasversale costrizione aortica, o possono essere studiati in modelli genetici di cardiomiopatia dilatativa 12. Ovviamente, il beneficio più pronunciato dei modelli murini ?...

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

L&#39;insufficienza cardiaca è una sindrome in cui il cuore non riesce a pompare il sangue ad una velocità al fabbisogno di ossigeno cellulari a riposo o durante lo stress. E &#39;caratterizzata da ritenzione di liquidi, mancanza di respiro, e la fatica, in particolare da sforzo. Lo scompenso cardiaco è un problema crescente di salute pubblica, la principale causa di ospedalizzazione, e una delle principali cause di mortalità. Cardiopatia ischemica è la principale causa di insufficienza cardiaca. Rimodellamento ventricolare riferisce alle variazioni di struttura, la dimensione e la forma del ventricolo sinistro. Questo rimodellamento architettonica del ventricolo sinistro è indotta da lesioni (es, infarto del miocardio), da sovraccarico di pressione (per esempio, ipertensione arteriosa sistemica o stenosi aortica), o da sovraccarico di volume. Dal rimodellamento ventricolare colpisce stress di parete, ha un profondo impatto sulla funzione cardiaca e sullo sviluppo di insufficienza cardiaca. Un modello di legatura permanente del descendin anteriore sinistrag coronarica nei topi è utilizzato per studiare il rimodellamento ventricolare e della funzione cardiaca dopo infarto miocardico. Questo modello è fondamentalmente diverso in termini di obiettivi e di rilevanza fisiopatologica rispetto al modello di legatura transitoria della discendente anteriore dell&#39;arteria coronaria. In questo secondo modello di danno da ischemia / riperfusione, la portata iniziale dell&#39;infarto può essere modulata da fattori che influenzano salvataggio miocardico seguente riperfusione. Al contrario, l&#39;area infartuata a 24 ore dopo la legatura permanente della discendente anteriore dell&#39;arteria coronaria è fisso. La funzione cardiaca in questo modello sarà influenzato dal 1) il processo di espansione infarto, infarto guarigione, e la formazione di cicatrici; e 2) lo sviluppo concomitante di dilatazione del ventricolo sinistro, ipertrofia cardiaca, e rimodellamento ventricolare. Oltre il modello di legatura permanente della discendente anteriore dell&#39;arteria coronaria, la tecnica invasiva emodinamico meamisura- nei topi è presentato in dettaglio.

L&#39;estensione di infarto del miocardio può essere valutata Evans blue / cloruro di 2,3,5-trifeniltetrazolio (TTC) doppia colorazione. TTC è un indicatore redox, che viene convertito in rosso scuro 1,3,5-triphenylformazan nei tessuti a causa della attività di vari deidrogenasi in presenza di NADH 8 vivente. La Figura 1 mostra una sezione rappresentativa del cuore a 24 ore dopo legatura del discendente anteriore dell&#39;arteria coronaria. Aree blu macchiato indicano regioni non-ischemich...

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.

Legatura permanente dell&#39;arteria discendente anteriore sinistra coronarica nei topi: un modello di post-infarto rimodellante miocardico e insufficienza cardiaca

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

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

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

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

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

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

Legatura dell&#39;arteria coronarica e di iniezione intramiocardico in un modello murino di 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 ...

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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.

L&#39;applicazione di permanente legatura dell&#39;arteria cerebrale media nel 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.

Tecnica modificata di legatura dell&#39;arteria coronarica in Mouse

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

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

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

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

Un modello murino di ischemia miocardica e riperfusione lesioni da legatura della arteria discendente anteriore sinistra

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 discendente anteriore sinistra (LAD) Coronary legatura dell&#39;arteria: una migliore e semplificata del modello di infarto miocardico

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.

Diretto Re-impianto di sinistra coronarica nell&#39;aorta in Adulti con Anomala origine della coronaria sinistra dall&#39;arteria polmonare (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.

Modello di infarto miocardico Murine utilizzando la legatura permanente dell'arteria coronaria discendente anteriore sinistra

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.

Istituzione di un modello suina di infarto post-miocardico per il trattamento delle cellule staminali

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.

Infarto post-miocardico Insufficienza cardiaca in occlusione coronarica a torace chiuso/ modello di riperfusione nei minipig di Gottinga e nei maiali 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.

Generazione e caratterizzazione dell'infarto miocardico ventricolare destro indotto dalla legatura permanente dell'arteria coronaria destra nei topi

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