Ringraziamo Fred Roberts e Chris White per il supporto tecnico esemplare. Ringraziamo di Brigham Women Hospital fisiologia cardiovascolare di base per fornire con la strumentazione ed i fondi per questo lavoro. Questo lavoro è stato sostenuto in parte da NHLBI concede HL093148, HL086967, e HL 088.533 (RL), K99HL107642 e la Fondazione Ellison (SC).

Procedura chirurgica <ol><li> Ottenere 8 settimane vecchio maschio C57BL / 6 topi e ambientarsi per una settimana prima vengono eseguite tutte le procedure sperimentali. </li><li> Prima della rappresentazione, occlusione dell&#39;arteria polmonare viene eseguita come descritto in precedenza 14, in conformità alle linee guida AVMA e approvato i protocolli IACUC. Le immagini ecocardiografiche Acquisizione e Misure Tutte le abbreviazioni utilizzate sono riassunti nella Tabella 1. </li></ol> 1. Parasternale asse lungo (plax) M modalità di visualizzazione per ottenere RV Sezione dimensione, accorciamento frazionale (FS), e RV Spessore parete <ol><li> Usa impostazione della modalità B per ottenere una completa LV parasternale asse lungo. Con l&#39;animale giace in posizione supina sulla piattaforma (vedi nota 6.1. E 6.2.), Posizionare la sonda ad ultrasuoni 40 MHz (MS550D) sull&#39;animale con circa 30 ° in senso antiorario per la linea parasternale sinistra con la tacca che indica la direzione caudale ( <strong&gt; Figura 1A). Regolare l&#39;angolo sonda inclinando leggermente lungo asse y della sonda (Figura 1D) per ottenere un pieno camera LV nel centro dello schermo. </li><li> Una volta che i punti di riferimento adeguati (RV, LV, MV, Ao, LA), come illustrato nelle figure 2A e 2B sono chiaramente visualizzate, passare alla modalità M. Una linea indicatore mostra sullo schermo in ambito M Mode. La linea deve essere posizionato a passare attraverso la parte più ampia della camera RV utilizzando Ao come punto di riferimento (Figure 2A e B). </li><li> In questa prospettiva, il muro camper e IVS devono essere chiaramente visibili. Assicurarsi che la profondità di messa a fuoco si trova nel centro della camera RV. Registrare i dati con negozio di cine per la dimensione della camera RV misura, FS e lo spessore della parete RV off line. Esempi di immagini M Mode sono mostrati nelle Figure 2C e 2D. (Vedi Nota 6.3.) </li></ol> 2. Parasternale asse corto View at MidLivello papillare ottenere frazionale Area Changes (FAC) <ol><li> Dalla posizione sopra descritta (Figura 1A), passare alla modalità B e ruotare la sonda di 90 ° in senso orario per avere la asse corto parasternale (Figura 1B). Pendere la sonda leggermente lungo l&#39;asse x della sonda per impedire la vista ostruttiva dello sterno. </li><li> Spostare leggermente verso l&#39;alto e verso il basso lungo l&#39;asse y della sonda per ottenere la metà del livello papillare (Vedi Nota 6.4.) </li><li> In questa prospettiva, i muscoli papillari si trovano di solito nella posizione 2 e 5:00 (Figura 3). </li></ol> 3. Parasternale asse corto View a valvola aortica livello (RV PSAX aortica Level) per ottenere RV Spessore parete e PA Peak Velocity <ol><li> Dalla posizione descritta sopra (Figura 1B), spostare la sonda a l&#39;asse y verso cranio finché la sezione trasversale della valvola aortica mostra nel centro della finestra. </li><li> Efflusso del ventricolo destro tract (RVOT) dovrebbe essere visibile sulla parte superiore come una struttura a forma di mezzaluna con valvola tricuspide separa la RV da RA come illustrato nelle figure 4A e B 2. Registrare i dati utilizzando negozio cine per la misurazione dello spessore della parete RV off line. (Vedi Nota 6.5.) </li><li> Rimanere nella stessa posizione. (Vedi Nota 6.6.) </li><li> Passare alla Modalità colore Doppler e posizionare il giallo PW-linea tratteggiata parallela alla direzione di flusso nel vaso. Si noti che i colori blu e rosso indicano defluire da e verso la sonda, rispettivamente (Figure 4C e D 4). </li><li> Posizionare il cursore PW sulla punta dei lembi valvolari polmonari. (Vedi Nota 6.7.) Registrare i dati utilizzando negozio cine. Misurare il picco di velocità PA off line. </li></ol> 4. Modificato parasternale lungo l&#39;asse Veduta di camper e PA ottenere PA Peak Velocity <ol><li> Proseguire sulla impostazione della modalità B, posizionare la sonda (MS550D o MS250) A destra linea parasternale (Figura 1C) e lentamente titolo sonda circa 30-45 gradi ° su l&#39;asse y della sonda (Figura 1D) verso il petto dei topi di visualizzare chiaramente il crossing over PA aorta come illustrato nelle figure 5A e 5 B. </li><li> Passare alla Modalità colore Doppler e posizionare il giallo PW-linea tratteggiata parallela alla direzione di flusso nel vaso (figure 5C e 5 D). Posizionare il cursore PW sulla punta dei lembi valvolari polmonari. (Vedi Nota 6.6.) Registrare i dati utilizzando negozio cine e misurare il picco di velocità PA off line. </li></ol> 5. Calcolo e analisi dei dati <ol><li> Spessore della parete RV può essere calcolata in base ai dati del modo B ottenuti da RV PSAX livello aortico come descritto in precedenza (protocollo 3). Selezionare lo strumento rintracciamento zona 2D per tracciare l&#39;area della parete RV in diastole (come mostrato nella zona rosa nella figura 6). Quindi, utilizzare lo strumento distanza tracciamento per tracciare le circonferenze interne ed esterne della parete di RVOT (come mostrato in linee blu in Figura 6). Prendere la media delle circonferenze interne ed esterne. Utilizzando l&#39;equazione <img fo:content-width="0.8in" src="/files/ftp_upload/51041/RVW_Thickness.jpg" width="80px" /> , Calcoliamo RV Wall (RVW) di spessore. (Vedi Nota 6.8.) </li><li> Per gli altri parametri standard, si prega di consultare i manuali dal rispettivo fabbrica per eseguire l&#39;analisi dei dati. </li></ol> 6. Note <ol><li> Tutte le immagini sono raccolte utilizzando il sistema Vevo 2100. Immagini simili possono essere ottenuti utilizzando sistemi di imaging a ultrasuoni da altri produttori, ed i relativi pro e contro dei vari strumenti ad ultrasuoni sono stati precedentemente confrontati 8,12,15. Si raccomanda che tutte le immagini devono essere ottenuti e analizzati in cieco quando possibile. </li><li> La scelta appropriata di anestesia, come un corto dfigurazione di isoflurano per via inalatoria (2-3% per indurre, e 1,0% per mantenere) è cruciale nel mantenimento del battito cardiaco a tassi fisiologici normali (superiori a 500 battiti / min), che ci permette di rilevare basale riproducibili e coerenti e polmonare arteriosa elevata pressione sistolica nello studio. </li><li> Assicurati di raccogliere i dati al più alto frame rate possibile possibile (&gt; 200 fotogrammi / sec). </li><li> Cercare la vista con la dimensione della camera più grande. </li><li> L&#39;ostruzione a causa di costole e lo sterno in gran parte dovuto alla posizione retrosternale del RV è il singolo più grande ostacolo ad ottenere immagini eccellenti in questo metodo di imaging del RV. Riposizionando l&#39;animale o la sonda, un operatore può superare il blocco sternale e ottenere viste necessari del RV. Questo può richiedere da 5-15 minuti, a seconda della fisiologia dell&#39;animale. </li><li> Potrebbe essere necessario cambiare sonda MS250 poiché sonda MS550D può essere utilizzato in sham e topi prima PAC e la sonda 40 MHz è in grado di registrarevelocità di picco di 300-1,500 m / sec, mentre MS250 è in grado di catturare la velocità parco fino a 4.000 mm / sec. </li><li> È accettabile un angolo sonda inferiore a 20 ° per la misurazione della velocità di picco PA. </li><li> Misure consistenti di spessore per camper e dintorni / dimensioni sono stati realizzati utilizzando più finestre acustiche, sia nel lungo e corto asse. La scelta di alcune di queste finestre dipende dall&#39;esperienza dell&#39;operatore, e potrebbe spiegare la variabilità che potrebbe essere che contribuisce a diversi risultati statistici. </li></ol>

<ol>
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Non c&#39;è nulla da rivelare.

Dimostriamo che TTE fornisce una metodologia sensibile e riproducibile per la valutazione di routine della struttura del camper e della funzione nei topi. Prima dell&#39;avvento della TTE, studi della RV in gran parte concentrati su misura RVSP tramite cateterismo cardiaco destro, un terminale e procedura invasiva 6,9,11,17. Rapporti precedenti hanno descritto una varietà di tecniche per la misurazione del cuore destro 3,4,11,17-19. Tuttavia, la maggior parte degli stu...

Storicamente, la valutazione prognostica dell&#39;insufficienza cardiaca è concentrata sul LV, che è facile da immagine tramite ecocardiografia. Numerosi studi sulla struttura LV e funzione con ecocardiografia hanno portato alla creazione di valori normali per la struttura LV e funzionamento 1,5,6. Misure di dimensioni LV e funzione sistolica ottenute da immagini bidimensionali e Color Doppler sono di grande importanza in quanto consentono delimitazione visiva dei compartimenti e geometria in grande dettaglio per la LV 7. M-Mode viene spesso utilizzato per misurare le dimensioni di LV e frazione di accorciamento (FS) nei topi. Inter-osservatore e la variabilità intra-osservatore sono bassi per le misure di diametro utilizzando questa modalità, ma misure di spessore della parete tendono ad essere piuttosto variabile 7. Doppler pulsato con il colore (PW o Color Doppler) è stato utilizzato per valutare rigurgito valvolare 8,9. Simili LV, RV gioca un ruolo importante ed è un significativo predictor di morbilità e mortalità nei pazienti affetti da 1,7,10 malattie cardiopolmonari. Tuttavia, la valutazione ecocardiografica di RV è intrinsecamente difficile a causa della sua complessa forma 5,11 e la sua posizione retrosternale che blocca le onde ultrasoniche 8,9. RV è una forma di mezzaluna struttura avvolgimento intorno al LV e ha un&#39;anatomia complessa con pareti sottili che sono abituati a bassa pressione e la resistenza a vasi polmonari 6. Per superare la resistenza vascolare elevata (PVR), il RV primo aumenta di dimensioni e subisce ipertrofie. Nelle malattie croniche come l&#39;ipertensione polmonare o malattia vascolare polmonare, RV subisce una dilatazione progressiva, eventualmente conseguente deterioramento della funzione sistolica e diastolica 4,5,10. L&#39;ecocardiografia svolge un ruolo importante nello screening e la diagnosi di PAH nonostante alcune limitazioni presenti nella sua capacità diagnostica clinica. Il vantaggio principale diTTE risiede nel fatto che è non invasiva e che può essere eseguita su leggermente sedato, o animali anche coscienti 9. TTE fornisce anche una stima ragionevole delle pressioni PA, nonché una valutazione continua dei cambiamenti nella struttura e funzione 12,13 RV. Grazie ai progressi tecnici in TTE, che includono lo sviluppo di sonde meccaniche ad alta frequenza, che consente la risoluzione assiale di circa 50 micron ad una profondità di 5-12 mm, frame rate elevati (superiori a 300 frame / sec), e alti tassi di campionamento , ecocardiografia è uno strumento ideale per l&#39;imaging in rapida contraente dimensioni del mouse cuore 8,11 piccolo. Monitoraggio longitudinale della funzione RV utilizzare più visualizzazioni, di cui 2-dimensionali (2D) l&#39;asse corto e lungo, M-mode e Doppler finestre acustiche fornire informazioni complementari di RV anatomia e la funzione. Collettivamente, questa metodologia consente di valutare completo longitudinale di emodinamica RV in fisiologia e l&#39;impostazione patologica <sup&gt; 4,7. Qui, mettiamo a disposizione una metodologia dettagliata step-by-step di usare TTE non invasiva per caratterizzare RV anatomiche e modifiche funzionali secondarie al PAC nei topi.

<table border="0" cellpadding="0" cellspacing="0" width="609">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="61">
			<td height="61" style="height:61px;width:157px;">High Frequency Ultrasound</td>
			<td style="width:108px;">FUJIFILM VisualSonics, Inc.</td>
			<td style="width:96px;">Vevo 2100</td>
			<td style="width:248px;"></td>
		</tr>
		<tr height="60">
			<td height="60" style="height:60px;width:157px;">High-frequency Mechanical Transducer</td>
			<td style="width:108px;">FUJIFILM VisualSonics, Inc.</td>
			<td style="width:96px;">MS250, MS550D, MS400</td>
			<td style="width:248px;"></td>
		</tr>
		<tr height="67">
			<td height="67" style="height:67px;width:157px;">Millar Mikro Pressure Catheter</td>
			<td style="width:108px;">Millar</td>
			<td style="width:96px;">SPR-1000</td>
			<td style="width:248px;"></td>
		</tr>
	</tbody>
</table>

assessment of right ventricular structure and function in mouse model of pulmonary artery constriction by transthoracic echocardiography

Emergenti dati clinici supportano l&#39;idea che la disfunzione RV è fondamentale per la patogenesi di malattie cardiovascolari e insufficienza cardiaca 1-3. Inoltre, la RV è significativamente influenzato in malattie polmonari come ipertensione arteriosa polmonare (PAH). Inoltre, la RV è notevolmente sensibile alle patologie cardiache, incluso ventricolo sinistro (LV) disfunzione, malattia valvolare o RV miocardico 4. Per comprendere il ruolo di RV nella patogenesi di malattie cardiache, un metodo affidabile e non invasiva per accedere al RV strutturalmente e funzionalmente è essenziale. Una metodologia ecocardiografia trans-toracica non invasivo (TTE) in base è stato stabilito e convalidato per il monitoraggio dei cambiamenti dinamici nella struttura e nella funzione camper in topi adulti. Per imporre lo stress RV, abbiamo impiegato un modello chirurgico di costrizione dell&#39;arteria polmonare (PAC) e misurato la risposta RV per un periodo di 7 giorni, con una ecografia microimaging ad alta frequenzasistema. Sham operati topi sono stati usati come controlli. Le immagini sono state acquisite in topi anestetizzati leggermente al basale (prima della chirurgia), giorno 0 (immediatamente post-chirurgico), il giorno 3 e il giorno 7 (post-chirurgico). I dati sono stati analizzati utilizzando il software offline. Diverse finestre acustiche (B, M, e modalità Color Doppler), che possono essere costantemente ottenuti nei topi, ha permesso per la misurazione affidabile e riproducibile di struttura RV (tra cui spessore della parete RV, fine diastole e le dimensioni finali-sistolica) e funzionali ( variazione frazionale zona, frazione di accorciamento, velocità di picco PA, e il gradiente di pressione di picco) in topi normali e dopo PAC. Usando questo metodo, la tensione-gradiente risultante dalla PAC è stata accuratamente misurata in tempo reale utilizzando la modalità Color Doppler ed era paragonabile a misurazioni della pressione scalo eseguite con alta fedeltà micropunte catetere Millar. Presi insieme, questi dati dimostrano che le misure RV ottenute da varie complvista imentary utilizzano l&#39;ecocardiografia sono affidabili, riproducibili e possono fornire spunti per quanto riguarda la struttura e la funzione RV. Questo metodo consentirà una migliore comprensione del ruolo di RV disfunzione cardiaca.

In questo studio, ecocardiografia basale è stata eseguita 48 ore prima dell&#39;intervento. I topi sono stati randomizzati in due gruppi. Topi ha ricevuto occlusioni dell&#39;arteria polmonare (PAC) e le operazioni fittizie (Sham). L&#39;ecocardiografia è stata eseguita al giorno 0, 3, 7 e seguente procedura chirurgica. Gli animali sono stati sacrificati immediatamente dopo l&#39;ultima ecocardiografia e il cuore sono state raccolte per la valutazione istologica. Cateterizzazione è stata condotta nel sottogruppo (n =...

Watch this Scientific Journal Video about Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography at JoVE.com

Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Ventricolo destro (RV) La disfunzione è fondamentale per la patogenesi della malattia cardiovascolare, ma le metodologie non sono disponibili per la sua valutazione. I recenti progressi nella ecografica forniscono un&#39;opzione non invadente e preciso per lo studio RV longitudinale. Qui, abbiamo dettaglio un metodo step-by-step ecocardiografico utilizzando un modello murino di sovraccarico di pressione RV.

Valutazione del ventricolo destro Struttura e funzione in modello murino di polmonare Arteria Costrizione da ecocardiografia transtoracica

Emerging clinical data support the notion that RV dysfunction is critical to the pathogenesis of cardiovascular disease and heart failure1-3. Moreover, ...

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27.4K Views.  Harvard Medical School.  Ventricolo destro (RV) La disfunzione è fondamentale per la patogenesi della malattia cardiovascolare, ma le metodologie non sono disponibili per la sua valutazione. I recenti progressi nella ecografica forniscono un'opzione non invadente e preciso per lo studio RV longitudinale. Qui, abbiamo dettaglio un metodo step-by-step ecocardiografico utilizzando un modello murino di sovraccarico di pressione RV. 

Video: Assessment of Right Ventricular Structure and Function in Mouse Model of Pulmonary Artery Constriction by Transthoracic Echocardiography

Transthoracic Echocardiography in Mice

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene expression. Transgenic and gene targeting methods can be used to generate mice with altered cardiac size and function,1-3 and as a result, in vivo techniques are needed to evaluate their cardiac phenotype. Transthoracic echocardiography, pulse wave Doppler (PWD), and tissue Doppler imaging (TDI) can be used to provide dimensional measurements of the mouse heart and to quantify the degree of cardiac systolic and diastolic performance. Two-dimensional imaging is used to detect abnormal anatomy or movements of the left ventricle, whereas M-mode echo is used for quantification of cardiac dimensions and contractility.4,5 In addition, PWD is used to quantify localized velocity of turbulent flow,6 whereas TDI is used to measure the velocity of myocardial motion.7 Thus, transthoracic echocardiography offers a comprehensive method for the noninvasive evaluation of cardiac function in mice.

Transthoracic echocardiography offers a noninvasive method for the evaluation of cardiac function in mice. A combination of ultrasound and Doppler imaging modalities can be used to obtain dimensional measurements of the heart and intracardiac blood flow, which together provide an assessment of cardiac systolic and diastolic performance.

L&#39;ecocardiografia transtoracica in topi

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene ...

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Echocardiographic Assessment of the Right Heart in Mice

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential therapies. Given the expense and time involved in creating animal models of disease, it is critical that researchers have tools to accurately assess phenotypic expression of disease. Right ventricular dysfunction is the major manifestation of pulmonary hypertension. Echocardiography is the mainstay of the noninvasive assessment of right ventricular function in rodent models and has the advantage of clear translation to humans in whom the same tool is used. Published echocardiography protocols in murine models of PAH are lacking.
In this article, we describe a protocol for assessing RV and pulmonary vascular function in a mouse model of PAH with a dominant negative BMPRII mutation; however, this protocol is applicable to any diseases affecting the pulmonary vasculature or right heart. We provide a detailed description of animal preparation, image acquisition and hemodynamic calculation of stroke volume, cardiac output and an estimate of pulmonary artery pressure.

This article provides a protocol for the echocardiographic assessment of right ventricular size and pulmonary hypertension in mice. Applications include phenotype determination and serial assessment in transgenic and toxin-induced mouse models of cardiomyopathy and pulmonary vascular disease.

La valutazione ecocardiografica del cuore destro in topi

Transgenic and toxic models of pulmonary arterial hypertension (PAH) are widely used to study the pathophysiology of PAH and to investigate potential ...

Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Right Ventricular (RV) dysfunction were induced in piglets by progressive obstruction of the pulmonary arteries. Consequences were remarkably similar to those observed in CTEPH patients. This animal model would be a very useful tool for pathophysiology and therapeutic experiments on CTEPH and RV failure.

Tromboembolica cronica Ipertensione polmonare e valutazione dei ventricolare destra Funzione nel Maialino

An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. ...

Transthoracic Speckle Tracking Echocardiography for the Quantitative Assessment of Left Ventricular Myocardial Deformation

The value of conventional echocardiography is limited by differences in inter-individual image interpretation and therefore largely dependent on the examiners&#39; expertise. Speckle tracking Echocardiography (STE) is a promising but technically challenging method that can be used to quantitatively assess regional and global systolic and diastolic myocardial performance. Myocardial strain and strain rate can be measured in all three dimensions&#160;&#8212; radial, circumferential, longitudinal &#8212; of myocardial deformation. Standard cross-sectional two-dimensional B-mode images are recorded and subsequently postprocessed by automated continuous frame-by-frame tracking and motion analysis of speckles within the myocardium. Images are recorded as digital loops and synchronized to a 3-lead EKG for timing purposes. Longitudinal deformation is assessed in the apical 4-, 3-, and 2-chamber views. Circumferential and radial deformation are measured in the parasternal short axis plane.
Optimal image quality and accurate tissue tracking are paramount for the correct determination of myocardial performance parameters. Utilizing transthoracic STE in a healthy volunteer, the present article is a detailed outline of the essential steps and potential pitfalls of quantitative echocardiographic myocardial deformation analysis.

Speckle tracking echocardiography is an emerging diagnostic imaging technique for the quantitative assessment of global and regional myocardial performance. Standard view echocardiographic motion images are recorded and deformation parameters are subsequently measured by automated continuous frame-by-frame tracking and motion analysis of speckles within the B-mode images of the myocardium.

Transtoracica Speckle monitoraggio ecocardiografia per la valutazione quantitativa del ventricolo sinistro del miocardio Deformazione

The value of conventional echocardiography is limited by differences in inter-individual image interpretation and therefore largely dependent on the ...

Murine Echocardiography of Left Atrium, Aorta, and Pulmonary Artery

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic pressure through echocardiography, as well as to obtain measurements of the Aorta and PA diameter in mice.
Mice older than 10 d of age can be analyzed using the present technique. The technique is composed of 3 main steps: set-up, image acquisition, and image analysis. The set-up step consists of getting the mouse anesthetized with 1% isoflurane, shaving it, and taping it in a supine position to a heated EKG board where the image acquisition will take place. The image acquisition step consists of learning to identify the cardiac structures and obtaining all the required images with its correspondent probe and axis in order to be able to calculate volumes and diameters. The image analysis step consists of measuring the previously acquired images with the aid of computer software.
Advantages of the proposed technique include a fast (15 min) procedure that would allow the researcher to evaluate interventions in a non-invasive, non-terminal approach and therefore follow the same mouse over time; each mouse can be used as its own control. This fact plus having the same operator perform all the acquisition and analysis for the entire experiment minimizes the limitation of operator-dependency. The present methodology is useful for mouse researchers in cardiovascular and pulmonary medicine.

The following protocol describes the methodology for the acquisition and analysis of echocardiographic images used to obtain the Left Atrial Volume (LAV), Aorta (Ao) diameter, and Pulmonary Artery (PA) diameter in mice. This technique is a non-invasive, non-terminal procedure that allows assessment of the cardiopulmonary function.

Murine ecocardiografia di Sinistra Atrium, Aorta, e l&#39;arteria polmonare

The present methodology teaches the investigator how to measure and use the LAV as a surrogate of chronic elevations in Left Ventricular diastolic ...

A Pulmonary Trunk Banding Model of Pressure Overload Induced Right Ventricular Hypertrophy and Failure

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary disorders. Reliable and reproducible animal models of RV failure are therefore warranted in order to investigate disease mechanisms and effects of potential therapeutic strategies. Banding of the pulmonary trunk is a common method to induce isolated RV hypertrophy but in general, previously described models have not succeeded in creating a stable model of RV hypertrophy and failure.
We present a rat model of pressure overload induced RV hypertrophy caused by pulmonary trunk banding (PTB) that enables different phenotypes of RV hypertrophy with and without RV failure. We use a modified ligating clip applier to compress a titanium clip around the pulmonary trunk to a pre-set inner diameter. We use different clip diameters to induce different stages of disease progression from mild RV hypertrophy to decompensated RV failure.
RV hypertrophy develops consistently in rats subjected to the PTB procedure and depending on the diameter of the applied banding clip, we can accurately reproduce different disease severities ranging from compensated hypertrophy to severe decompensated RV failure with extra-cardiac manifestations.
The presented PTB model is a valid and robust model of pressure overload induced RV hypertrophy and failure that has several advantages to other banding models including high reproducibility and the possibility of inducing severe and decompensated RV failure.

We present a surgical method to induce right ventricular hypertrophy and failure in rats.

Un tronco polmonare Banding modello di sovraccarico pressorio indotto da fallimento e ipertrofia ventricolare destra

Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary ...

Isometric Contractility Measurement of the Mouse Mesenteric Artery Using Wire Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K+ solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K+ solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K+ solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

The wire myograph technique is used to investigate vascular smooth muscle functions and screen new drugs. We report a detailed protocol for measuring the isometric contractility of the mouse mesenteric artery and for screening new relaxants of vascular smooth muscle.

Misurazione di contrattilità isometrica dell'arteria mesenterica Mouse con filo Myography

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and ...

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

Valutazione emodinamica invasiva per il sistema ventricolare destro e l'ipertensione arteriosa polmonare indotta dall'ipossia nei topi

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. ...

Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography

Traditionally, it was believed that the right side of the heart has a minor role in circulation; however, more and more data suggest that right ventricular (RV) function has strong diagnostic and prognostic power in various cardiovascular disorders. Due to its complex morphology and function, assessment of the RV by conventional two-dimensional echocardiography is limited: the everyday clinical practice usually relies on simple linear dimensions and functional measures. Three-dimensional (3D) echocardiography overcame these limitations by providing volumetric quantification of the RV free of geometrical assumptions. Here, we offer a step-by-step guide to obtain and analyze 3D echocardiographic data of the RV using the leading commercially available software. We will quantify 3D RV volumes and ejection fraction. Several technical aspects may help to improve the quality of RV acquisition and analysis as well, which we present in a practical manner. We review the current opportunities and the limiting factors of this method and also highlight the potential applications of 3D RV assessment in current clinical practice.

Here, we provide a step-by-step acquisition and analysis protocol for the 3D volumetric assessment of the right ventricle, mainly focusing on the practical aspects that maximize the feasibility of this technique.

Valutazione morfologica e funzionale del ventricolo destro mediante ecocardiografia 3D

Traditionally, it was believed that the right side of the heart has a minor role in circulation; however, more and more data suggest that right ...

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 ...