This work was supported by NIH grants HL111121 (JDM) and TR000954 (JDM).

<ol>
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The authors have nothing to disclose.

L&#39;invecchiamento è associato con aumenti progressivi nella calcificazione cardiovascolare 1. Emodinamicamente significativa stenosi della valvola aortica colpisce il 3% della popolazione di età superiore ai 65 2, e pazienti con anche moderata stenosi della valvola aortica (picco di velocità di 3-4 m / s) hanno una sopravvivenza libera da eventi a 5 anni del meno del 40% 3. Attualmente, non ci sono trattamenti efficaci per rallentare la progressione della calcificazione della valvola aortica, e chirurgica sostituzione della valvola aortica è l&#39;unico trattamento disponibile per Advanced valvola aortica Stenosi 4. Gli studi volti a ottenere una più profonda comprensione dei meccanismi che contribuiscono alla iniziazione e la progressione della calcificazione della valvola aortica sono un primo passo fondamentale nella transizione verso metodi farmacologici e non chirurgiche per la gestione della valvola aortica Stenosi 5, 6. geneticotopi ly-alterati hanno svolto un ruolo importante nello sviluppo della nostra comprensione dei meccanismi che contribuiscono a una varietà di malattie e sono ormai prossimi alla ribalta degli studi meccanicistici volti a comprendere la biologia di una stenosi della valvola aortica 6, 7, 8. A differenza di altre malattie cardiovascolari come l&#39;aterosclerosi e insufficienza cardiaca, dove i protocolli standard per la valutazione della funzione vascolare e ventricolare sono per la maggior parte ben consolidata, ci sono sfide uniche associate a fenotipizzazione in vivo della funzione valvola cardiaca nei topi. Mentre recensioni più recenti hanno fornito discussioni approfondite per quanto riguarda i vantaggi e gli svantaggi di numerose immagini e le modalità invasive utilizzate per valutare la funzione della valvola nei roditori 9, 10, 11, ad oggi, non siamo a conoscenza di una pubblicazione che fornisce una comprehensive, step-by-step di protocollo per la funzione della valvola cardiaca fenotipizzazione nei topi. Lo scopo di questo manoscritto è descrivere i metodi ei protocolli di fenotipo funzione della valvola cardiaca nei topi. Tutti i metodi e le procedure sono state approvate dal Comitato Istituzionale cura degli animali e Usa Mayo Clinic. I componenti chiave di questo protocollo sono la profondità dell&#39;anestesia, la valutazione della funzione cardiaca, e la valutazione della funzionalità delle valvole cardiache. Ci auguriamo che questo rapporto non solo servirà a guidare gli investigatori interessati a perseguire la ricerca nel campo delle malattie delle valvole cardiache, ma anche avviare un dialogo nazionale ed internazionale in materia di standardizzazione del protocollo per garantire la riproducibilità dei dati e la validità in questo settore in rapida crescita. È importante sottolineare che, imaging successo utilizzando sistemi a ultrasuoni ad alta risoluzione richiede una conoscenza dei principi di ecografia (e terminologia comunemente utilizzati in ecografia), una comprensione della Princip fondamentaleles di fisiologia cardiaca, e una significativa esperienza con ecografia per consentire una valutazione precisa e in tempi rapidi della funzione cardiaca nei roditori.

<table><tbody><tr><td>High resolution ultrasound machine</td><td>VisualSonics, Fujifilm</td><td>Vevo 2100&amp;nbsp;</td><td></td></tr><tr><td>Isoflurane diffuser (capable of delivering 1 % to 1.5 % isoflurane mixed with 1 L/min 100% O&lt;sub&gt;2&lt;/sub&gt;</td><td>VisualSonics, Fujifilm</td><td>N/A</td><td></td></tr><tr><td>Transducers for small mice (550D) or larger mice (400)</td><td>MicroScan, VisualSonics, Fujifilm</td><td>MS 550D, MS 400</td><td></td></tr><tr><td>Animal platform</td><td>VisualSonics, Fujifilm</td><td>11503</td><td></td></tr><tr><td>Advanced physiological monitoring unit</td><td>VisualSonics, Fujifilm</td><td>N/A</td><td></td></tr><tr><td>Isoflurane</td><td>Terrell</td><td>NDC 66794-019-10</td><td></td></tr><tr><td>Nose cone and tubing connected to isoflurane diffuser and 100% O&lt;sub&gt;2&lt;/sub&gt;</td><td>Custom Engineered in-house</td><td>--</td><td></td></tr><tr><td>Hair razor</td><td>Andis Super AGR+ vet pack clipper</td><td>AD65340</td><td></td></tr><tr><td>Ultrasound gel</td><td>Parker Laboratories</td><td>REF 01-08</td><td></td></tr><tr><td>Electrode gel&amp;nbsp;</td><td>Parker Laboratories</td><td>REF 15-25</td><td></td></tr><tr><td>Adhesive tapes</td><td>Fisher Laboratories</td><td>1590120B</td><td></td></tr><tr><td>Paper towels</td><td></td><td></td><td></td></tr></tbody></table>

echocardiographic approaches and protocols for comprehensive phenotypic characterization of valvular heart disease in mice

The aim of this manuscript and accompanying video is to provide an overview of the methods and approaches used for imaging heart valve function in rodents, with detailed descriptions of the appropriate methods for anesthesia, the echocardiographic windows used, the imaging planes and probe orientations for image acquisition, the methods for data analysis, and the limitations of emerging technologies for the evaluation of cardiac and valvular function. Importantly, we also highlight several future areas of research in cardiac and heart valve imaging that may be leveraged to gain insights into the pathogenesis of valve disease in preclinical animal models. We propose that using a systematic approach to evaluating cardiac and heart valve function in mice can result in more robust and reproducible data, as well as facilitate the discovery of previously underappreciated phenotypes in genetically-altered and/or physiologically-stressed mice.

Esempi di immagini che vengono abitualmente ottenuti da ecografica cardiaca animale sono inclusi in questo manoscritto. Un&#39;illustrazione di stage trasduttore sul petto dell&#39;animale viene fornito per dare al lettore una chiara comprensione di dove il trasduttore è posizionato per ottenere le immagini come descritto. Una fotografia del laboratorio ultrasuoni set-up è incluso anche sottolineare l&#39;importanza di attrezzatura, in particolare il trasduttore ad ultrasuoni da utilizzare e il metodo di anestesia. Il / B-modalità 2D, M-mode, e il colore e Doppler mostra dei normali e anormali valvole, ventricoli destro e sinistro, e la radice aortica sono adeguatamente etichettati. Sebbene l&#39;imaging velocità di deformazione non viene eseguita di routine, è anche incluso un esempio. rigurgito mitrale è caratterizzato da una velocità elevata, di solito non laminare flusso di sangue (colorazione mosaico) attraverso la valvola durante systole (Figura 5). La presenza di un tale modello di flusso Doppler mosaico colore dal ventricolo sinistro all&#39;atrio sinistro attraverso la MV, che si verificano dopo il complesso QRS nel tracciato ECG, consente una diagnosi inequivocabile di MR. Quando ciò si verifica in assenza di rigurgito della valvola aortica e / o disfunzione ventricolare sinistra, questo può essere caratterizzato come isolato prolasso della valvola mitrale. Se c&#39;è una significativa dilatazione del ventricolo sinistro (causa sperimentalmente indotta insufficienza cardiaca o eccessiva profondità dell&#39;anestesia), questo può essere caratterizzato come mitralica ischemica (o rigurgito secondaria a disfunzione cardiaca). Un display Doppler spettrale pulsato onda può essere utilizzata per confermare la presenza e la tempistica di un getto di rigurgito del flusso sanguigno. Una valvola aortica normale ha tre sottili cuspidi flessibili che aprono e chiudono adeguatamente durante ogni ciclo cardiaco. Aortica separazione valvola cuspide si misura in 2D-guidedM-mode della valvola aortica in asse lungo. Pinze elettronici sono utilizzati per misurare dal bordo anteriore della cuspide aortica fino al bordo anteriore della cuspide aortica sinistra (figura 3). valvola aortica distanza cuspide-separazione nei topi normali è 0,9 a 1,3 mm. Color Doppler mostra un flusso laminare attraverso la valvola e nella radice aortica durante la sistole. flusso turbolento può essere apprezzato in condizioni di maggiore flusso, come nel rigurgito della valvola aortica o aumento della pressione, come nella stenosi della valvola aortica. Questo è dimostrato come colorante mosaico nel tratto di efflusso. Anche piccole quantità di rigurgito della valvola aortica può portare a un aumento significativo della velocità di picco transvalvolare a causa di funzione cardiaca e aumento della iperdinamica sinistra precarico ventricolare. Peak velocità aortica nelle normali intervalli di topi da 0,90 m / s a ​​1,50 m / s. velocità di picco della valvola aortica di&gt; 5 m / s è stato registrato nei topi con grave stenosi valvolare aortica. <p class="jove_content" fo:keep-together.within-page = &quot;1&quot;&gt; I pulsato onda spettrali tracciati Doppler può anche essere utilizzato per fornire un indice di polmonare dell&#39;arteria emodinamica 12 (Figura 8). Polmonare tempo di accelerazione arteria è l&#39;intervallo di tempo dall&#39;inizio della sistolica flusso arteriosa polmonare alla velocità del flusso di picco. Proprio tempo di eiezione ventricolare è l&#39;intervallo tra l&#39;insorgenza di eiezione ventricolare destra al punto in cui vi è la cessazione del flusso sistolica sistolica dell&#39;arteria polmonare. La combinazione di un tempo di accelerazione arteria polmonare abbreviato con una diminuzione del rapporto tra tempo di accelerazione polmonare a destra tempo eiezione ventricolare suggerisce la presenza di ipertensione arteriosa polmonare (che può essere confermato mediante misure invasive o direttamente su arteriosa polmonare o pressione ventricolare destra) . <img alt="Figura 1" src="/files/ftp_upload/54110/54110fig1.jpg" /> Figura 1: Animal Cardiac Laboratorio ultrasuoni. Il laboratorio è attrezzato con la macchina a ultrasuoni piccolo-animale-dedicata con alta frequenza (30 MHz e 40 MHz) trasduttori (MS 400 e MS 550D), diffusore isoflurano, piattaforma di animali, la temperatura e il monitor della frequenza cardiaca, 1% al 1,5% isoflurano mescolato con 1 L / min 100% O 2, ogiva e tubo collegato al diffusore isoflurano e il 100% O 2, rasoio capelli, gel per ultrasuoni, gel per elettrodi, nastri adesivi, e tovaglioli di carta. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig1large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="figura 2" src="/files/ftp_upload/54110/54110fig2.jpg" /> Figura 2: trasduttore di base posizioni. Finestra (A) parasternale. La testa del trasduttore è posizionata nel bordo parasternale sinistra, con il marcatore indice di immagine del trasduttore diretto caudalmente. from questa posizione, l&#39;asse lungo del ventricolo sinistro, valvola aortica, e radice aortica e asse corto della valvola polmonare può essere ottenuta. (B) Dalla finestra parasternale, la testa trasduttore viene ruotato in senso antiorario, con la tacca rivolta posteriormente. Da questa posizione, l&#39;asse corto del ventricolo sinistro e la valvola aortica e l&#39;asse lungo della valvola polmonare può essere ottenuta. (C) apicale finestra. La testa trasduttore è posizionato all&#39;apice del cuore. Da questa posizione, l&#39;asse lungo del ventricolo sinistro e valvole mitrale e tricuspide destra e può essere ottenuto. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig2large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 3" src="/files/ftp_upload/54110/54110fig3.jpg" /> Figura 3: Valutazione della valvola aortica funzione in un Normal mouse contro Funzione valvola aortica in un mouse con calcifica aortica malattia di Valve. Immagine (A) 2D di una valvola aortica normale nel asse lungo. Si noti che la valvola aortica si apre bene durante la sistole. Immagine (B) M-mode raffigurante normale funzione della valvola aortica (aspetto a scatola). Si noti che la distanza cuspide-separazione viene misurata a 1.12 mm. Visualizzazione (C) Doppler spettrale di picco di velocità attraverso la valvola aortica normale è stato meaured a 1,3 m / s. Immagine (D) 2D di una valvola aortica calcificata nella vista lungo l&#39;asse da un recettore delle lipoproteine a bassa densità carente (LDLR - / -) e apolipoproteina B100-only (100/100 apoB) del mouse alimentati con dieta occidentale. Le cuspidi sono ispessite e sono aumentati ecogenicità, che si traduce in un&#39;apertura ristretta durante la sistole. (E) Un&#39;immagine M-mode raffigurante la stessa valvola aortica stenotica mostra una misurazione della distanza cuspide separazione di 0,7 mm. (F &lt;/ Strong&gt;) Il display Doppler spettrale di picco di velocità attraverso la valvola aortica stenotica stato meaured a 4.6 m / s. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig3large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 4" src="/files/ftp_upload/54110/54110fig4.jpg" /> Figura 4: M-mode di una valvola mitrale normale. Dalla finestra apicale, una visione a lungo l&#39;asse della valvola mitrale è ottenuto. La linea M-mode di interrogatorio viene applicata in tutto il volantino della valvola mitrale. Mentre spessore lembo mitralico può teoricamente essere misurata utilizzando calibri elettronici, questo può essere estremamente impegnativo dato il sottile, ecogeno male, e rapidamente volantini della valvola mitrale normale movimento. Le frecce indicano la M-mode del lembo della valvola mitrale in sistole. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig4large.jpg" target="_blank">Si prega di cli</a>ck qui per vedere una versione più grande di questa figura. <img alt="Figura 5" src="/files/ftp_upload/54110/54110fig5.jpg" /> Figura 5: La prova di una valvola mitrale rigurgitante Jet utilizzando Color Doppler Imaging. Dalla finestra parasternale, una visione a lungo l&#39;asse modificata della valvola mitrale è ottenuto. Color Doppler interrogatori mostra un getto mosaico colore alla valvola mitrale durante la sistole (indicata da una freccia). <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig5large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 6" src="/files/ftp_upload/54110/54110fig6.jpg" /> Figura 6: lungo l&#39;asse Vista la principale arteria polmonare e dei suoi rami principali. La visione a lungo l&#39;asse dell&#39;arteria polmonare principale (MPA) e destra (RPA) e sinistra rami (LPA) può essere ottenuto dal paraste<html> finestra rnal. Il diritto del tratto di efflusso del ventricolo (RVOT), valvola polmonare (PV), e l&#39;aorta (AO) sono in parte visibili. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig6large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 7" src="/files/ftp_upload/54110/54110fig7.jpg" /> Figura 7: M-mode immagine raffigurante una valvola polmonare normale. Dalla finestra parasternale, entrambe le viste a breve e lungo asse della valvola polmonare possono essere ottenuti. La linea M-mode di interrogatorio viene applicata attraverso la valvola polmonare. La distanza pulmonic valvola cuspide-separazione (frecce) può essere misurato da questo punto di vista. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig7large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> 10fig8.jpg &quot;/&gt; Figura 8: Pulsed Doppler interrogazione del flusso attraverso la valvola polmonare. Il tempo di accelerazione arteria polmonare (PAAT) è l&#39;intervallo di tempo dall&#39;inizio della sistolica flusso arterioso polmonare alla velocità di picco di flusso. tempo di eiezione ventricolare destro (RVET) è l&#39;intervallo tra l&#39;insorgenza di eiezione ventricolare destra al punto in cui c&#39;è cessazione del flusso. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig8large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 9" src="/files/ftp_upload/54110/54110fig9.jpg" /> Figura 9: M-mode immagine raffigurante un asse corto Veduta del ventricolo sinistro. Dalla finestra parasternale, l&#39;asse corto del ventricolo sinistro è ottenuta ruotando la testa trasduttore antiorario in modo che i punti di marcatura indice immagine posteriormente o dorsalmente. L&#39;M-mode linea di interrogazione è applicato attraverso il ventricolo sinistro a livello dei muscoli papillari. dimensione del ventricolo sinistro a fine diastole (LVEDD), del ventricolo sinistro telesistolico dimensione (LVESD), e la parete anteriore (AW) e spessori parete posteriore (PW) possono essere facilmente misurato. Fare attenzione a non includere il muscolo papillare (*) in qualsiasi misurazione. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig9large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 10" src="/files/ftp_upload/54110/54110fig10.jpg" /> Figura 10: Color Doppler Valutazione e pulsato Doppler spettrale Visualizzazione della valvola mitrale afflusso. (A) Immagine che mostra una valutazione color Doppler di flusso valvola mitrale nel apicale asse lungo. Si noti che l&#39;immagine a colori Doppler 2D può essere uno strumento fondamentale per gdebbono guidare la posizione volume di campione appropriato per l&#39;acquisizione di impulsi ad onda tracciati Doppler (raffigurata in pannello B). (B) visualizzazione spettrale del flusso della valvola mitrale tramite impulsi Doppler. La valutazione Doppler pulsato onda del flusso sanguigno attraverso la valvola mitrale (nel apicale asse lungo) viene eseguita per valutare ventricolare sinistra funzione diastolica. Il volume del campione è posto punte dei lembi della valvola mitrale. Il tempo isovolumic di rilassamento (IVRT), tempo di contrazione isovolumica (IVCT), ventricolare sinistra tempo di eiezione (LVET), e la velocità mitrale afflusso di picco (E) possono tutti essere derivata dalla visualizzazione spettrale di impulsi ad onda velocità Doppler attraverso la valvola mitrale. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig10large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 11" src="/files/ftp_upload/54110/54110fig11.jpg" /> Figura 11: Tissue Doppler Imaging del setto mitralica Annulus. Dalla finestra apicale, una visione a lungo l&#39;asse della valvola mitrale è ottenuto. Il volume del campione di tessuto Doppler è posizionato in corrispondenza della zona settale dell&#39;anello mitrale. Il rapporto tra la velocità di afflusso mitrale picco (variabile E in Figura 10B) e la velocità di picco mitrale tessuto annulus (e &#39;, indicato con frecce bianche) viene utilizzato per valutare ventricolare sinistra funzione diastolica (comunemente indicata come E / e&#39;). <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig11large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> <img alt="Figura 12" src="/files/ftp_upload/54110/54110fig12.jpg" /> Figura 12: Valutazione della Strain e Strain Rate del ventricolo sinistro miocardio. Ci sono pacchetti software di analisi specializzati disponibili in commercio, e le variabili di deformazione e velocità di deformazione può essereottenuto come misure di cambiamenti precoci o sub-clinici in intrinseche proprietà contrattili del miocardio. Gli esempi sopra riportati rappresentano deformazione radiale e velocità di deformazione in piani di imaging comunemente acquistati nei topi. Si noti che questi piani d&#39;immagine (e la successiva forma dei tracciati ceppo) possono differire dalle immagini negli esseri umani, che sono spesso acquisite nel lungo asse apicale o 4 per camera. <a href="https://ecsource-jove-com.bdigitaluss.remotexs.co/files/ftp_upload/54110/54110fig12large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a>

Watch this Scientific Journal Video about Echocardiographic Approaches and Protocols for Comprehensive Phenotypic Characterization of Valvular Heart Disease in Mice at JoVE.com

Echocardiographic Approaches and Protocols for Comprehensive Phenotypic Characterization of Valvular Heart Disease in Mice

This protocol provides a detailed description of the echocardiographic approach for comprehensive phenotyping of heart and heart valve function in mice.

Approcci ecocardiografici e protocolli per completa caratterizzazione fenotipica di malattia valvolare cardiaca nei topi

The aim of this manuscript and accompanying video is to provide an overview of the methods and approaches used for imaging heart valve function in ...

echocardiographic-approaches-protocols-for-comprehensive-phenotypic

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JoVE Journal

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15.9K Views.  Mayo Clinic. This protocol provides a detailed description of the echocardiographic approach for comprehensive phenotyping of heart and heart valve function in mice. 

Video: Echocardiographic Approaches and Protocols for Comprehensive Phenotypic Characterization of Valvular Heart Disease in Mice

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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Medicina

Murine Echocardiography and Ultrasound Imaging

Rodent models of cardiac pathophysiology represent a valuable research tool to investigate mechanism of disease as well as test new therapeutics.1 Echocardiography provides a powerful, non-invasive tool to serially assess cardiac morphometry and function in a living animal.2 However, using this technique on mice poses unique challenges owing to the small size and rapid heart rate of these animals.3 Until recently, few ultrasound systems were capable of performing quality echocardiography on mice, and those generally lacked the image resolution and frame rate necessary to obtain truly quantitative measurements. Newly released systems such as the VisualSonics Vevo2100 provide new tools for researchers to carefully and non-invasively investigate cardiac function in mice. This system generates high resolution images and provides analysis capabilities similar to those used with human patients. Although color Doppler has been available for over 30 years in humans, this valuable technology has only recently been possible in rodent ultrasound.4,5 Color Doppler has broad applications for echocardiography, including the ability to quickly assess flow directionality in vessels and through valves, and to rapidly identify valve regurgitation. Strain analysis is a critical advance that is utilized to quantitatively measure regional myocardial function.6 This technique has the potential to detect changes in pathology, or resolution of pathology, earlier than conventional techniques. Coupled with the addition of three-dimensional image reconstruction, volumetric assessment of whole-organs is possible, including visualization and assessment of cardiac and vascular structures. Murine-compatible contrast imaging can also allow for volumetric measurements and tissue perfusion assessment.

This video demonstrates use of a rail-mounted high-frequency ultrasound probe to perform echocardiography on an anesthetized mouse. The methods describe both conventional two-dimensional and M-mode measurements of cardiac function in addition to newer, more powerful tools such as color Doppler, strain analysis, as well as general and targeted contrast imaging.

L&#39;ecocardiografia murini e imaging a ultrasuoni

Rodent models of cardiac pathophysiology represent a valuable research tool to investigate mechanism of disease as well as test new therapeutics.1  ...

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 ...

A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse

Congenital heart diseases (CHDs) are major causes of infant death in the United States. In the 1980s and earlier, most patients with moderate or severe CHD died before adulthood, with the maximum mortality during the first week of life. Remarkable advances in surgical techniques, diagnostic approaches, and medical management have led to marked improvements in outcomes. To address the critical research needs of understanding congenital heart defects, murine models have provided an ideal research platform, as they have very similar heart anatomy to humans and short gestation rates. The combination of genetic engineering with high-throughput phenotyping tools has allowed for the replication and diagnosis of structural heart defects to further elucidate the molecular pathways behind CHDs. The use of noninvasive fetal echocardiography to screen the cardiac phenotypes in mouse models coupled with the high fidelity of Episcopic fluorescence image capture (EFIC) using Episcopic confocal microscopy (ECM) histopathology with three-dimensional (3D) reconstructions enables a detailed view into the anatomy of various congenital heart defects. This protocol outlines a complete workflow of these methods to obtain an accurate diagnosis of murine congenital heart defects. Applying this phenotyping protocol to model organisms will allow for accurate CHD diagnosis, yielding insights into the mechanisms of CHD. Identifying the underlying mechanisms of CHD provide opportunities for potential therapies and interventions.

This article details murine congenital heart disease (CHD) diagnostic methods using fetal echocardiography, necropsy, and Episcopic fluorescence image capture (EFIC) using Episcopic confocal microscopy (ECM) followed by three-dimensional (3D) reconstruction.

Una pipeline per caratterizzare i difetti cardiaci strutturali nel topo fetale

Congenital heart diseases (CHDs) are major causes of infant death in the United States. In the 1980s and earlier, most patients with moderate or severe ...

Biologia dello sviluppo

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable noninvasive method is essential to assess real-time cardiac morphological and functional changes in animal models of heart disease. Transthoracic echocardiography represents an important tool for noninvasive assessment of cardiac structure and function2. Here we used a high-resolution ultrasound imaging system to monitor myocardial remodeling and heart failure progression over time in a mouse model of TAC. B-mode, M-mode, and Doppler imaging were used to precisely assess cardiac hypertrophy, ventricular dilatation, and functional deterioration in mice following TAC. Color and pulse wave (PW) Doppler imaging was used to noninvasively measure pressure gradient across the aortic constriction created by TAC and to assess transmitral blood flow in mice. Thus transthoracic echocardiographic imaging provides comprehensive noninvasive measurements of cardiac dimensions and function in mouse models of heart disease.

The goal of this protocol is to noninvasively assess cardiac structural and functional changes in a mouse model of heart disease created by transverse aortic constriction, using B- and M-mode echocardiography and color/pulse wave Doppler imaging.

Valutazione del Cardiac morfologiche e funzionali Variazioni modello murino di trasversale aortica costrizione da parte ecocardiografica Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable ...

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 ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

Esame ecocardiografico ed istologico della morfologia cardiaca nel topo

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV diastolic function is rarely quantified in experimental studies. This might be due to technical difficulties in the visualization of the RV in the apical four-chamber view in rodents. Here we describe two positions facilitating the visualization of the apical four-chamber view in mice to assess the RV diastolic function.
The apical four-chamber view is enabled by tilting the mouse fixation platform to the left and caudally (LeCa) or to the right and cranially (RiCr). Both positions provide images of comparable quality. The results of the RV diastolic function obtained from two positions are not significantly different. Both positions are comparably easy to perform. This protocol can be incorporated into published protocols and enables detailed investigations of the RV function.

Here we describe and compare two positions for obtaining the apical four-chamber view in mice. These positions enable the quantification of the right ventricular function, provide comparable results, and can be used interchangeably.

Misurazione ecocardiografica dei parametri diastolici ventricolari a destra nel mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV ...

Revealing Subtle Changes in Cardiac Function using Transthoracic Dobutamine Stress Echocardiography in Mice

Left ventricular (LV) dysfunction paves the final pathway for a multitude of cardiac disorders. With the non-invasive high-frequency transthoracic dobutamine stress echocardiography in humans, a reductionist investigation approach to unmask subtle changes in cardiac function has become possible. Here, we provide a protocol for using this technique in mice to facilitate expanded analysis of LV architecture and function in physiology and pathology enabling the observation of alterations in models of cardiac disease hidden in unstressed hearts. This investigation can be performed in one and the same animal and allows both, basal and pharmacologically stress-induced measurements. We outline detailed criteria for appropriate anesthesia, imaging-based LV analysis, consideration of intra- and interobserver variability, and obtaining positive inotrope response that can be attained in mice after intraperitoneal injection of dobutamine under near physiological conditions. To recapitulate the characteristics of human physiology and disease in small animal models, we highlight critical pitfalls in evaluation, e.g., a pronounced Bowditch effect in mice. To further meet translational objectives, we compare stress-induced effects in humans and mice. When used in translational studies, attention must be paid to physiological differences between mice and human. Experimental rigor dictates that some parameters assessed in patients can only be used with caution due to restrictions in spatial and temporal resolution in mouse models.

Left ventricular dysfunction constitutes the final common pathway for a host of cardiac disorders. We here provide a detailed protocol of transthoracic dobutamine stress echocardiography approach for comprehensive evaluation of the left ventricular function of mouse models of cardiac disease as well as cardiac phenotyping.

Left ventricular (LV) dysfunction paves the final pathway for a multitude of cardiac disorders. With the non-invasive high-frequency transthoracic ...

Echocardiographic Characterization of Left Ventricular Structure, Function, and Coronary Flow in Neonate Mice

Echocardiography is a non-invasive procedure that enables the evaluation of structural and functional parameters in animal models of cardiovascular disease and is used to assess the impact of potential treatments in preclinical studies. Echocardiographic studies are usually conducted in young adult mice (i.e., 4-6 weeks of age). The evaluation of early neonatal cardiovascular function is not usually performed because of the small size of the mouse pups and the associated technical difficulties. One of the most important challenges is that the short length of the pups&#39; limbs prevents them from reaching the electrodes in the echocardiography platform. Body temperature is the other challenge, as pups are very susceptible to changes in temperature. Therefore, it is important to establish a practical guide for performing echocardiographic studies in small mouse pups to help researchers detect early pathological changes and study the progression of cardiovascular disease over time. The current work describes a protocol for performing echocardiography in mouse pups at the early age of 7 days old. The echocardiographic characterization of cardiac morphology, function, and coronary flow in neonatal mice is also described.

The present protocol describes the echocardiographic assessment of left ventricular morphology, function, and coronary blood flow in 7-day old neonate mice.

Caratterizzazione ecocardiografica della struttura, della funzione e del flusso coronarico del ventricolo sinistro in topi neonati

Echocardiography is a non-invasive procedure that enables the evaluation of structural and functional parameters in animal models of cardiovascular ...

Approcci ecocardiografici e protocolli per completa caratterizzazione fenotipica di malattia valvolare cardiaca nei topi

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L'ecocardiografia transtoracica in topi

L'ecocardiografia murini e imaging a ultrasuoni