我々は典型的な、技術的なサポートのためにフレッド·ロバーツとクリス·ホワイトに感謝します。我々は、この作業のための機器および資金提供ブリガム·ウィメンズ病院心臓血管生理学のコアに感謝します。この作品は、NHLBIによって部分的にサポートされていました、K99HL107642とエリソン財団（SC）をHL093148、HL086967、およびHL 088533（RL）を付与します。

外科手術<ol><li> 8週齢の雄のC57BL / 6マウスを入手し、任意の実験手順が実行される前に1週間順化。 </li><li>画像化の前に、肺動脈閉塞はAVMAガイドラインに従って、以前に14を説明したように行い、動物実験委員会のプロトコルを承認されています。 心エコー画像の取得と測定 使用される全ての略号を表1にまとめる。 </li></ol> 1。傍胸骨長軸（PLAX）、Mモードの表示は、RV商工寸法、短縮率（FS）、およびRVの壁厚さを得るため<ol><li>フルLV胸骨傍の長軸像を得るために、Bモードの設定を使用してください。動物は（6.1をご参照ください。および6.2。）プラットフォーム上で仰臥位に横たわって、反時計回りにノッチが尾側方向を向いて左胸骨傍の行に約30°の角度で動物に40 MHzの超音波プローブ（MS550D）の位置に（ <strong&gt;図1A）。画面中央の完全なLV室ビューを得るために、プローブ（ 図1D）のy軸に沿ってわずかに傾けることによって、プローブの角度を調整します。 </li><li>適切なランドマーク（RV、LV、MV、AO、LA）後は、 図2Aおよび2Bに示されているように、明らかに、Mモードに切り替えて、可視化される。インジケーターラインは、Mモード設定で画面に表示されます。線は、（ 図2AおよびB）ランドマークとして青を使用して、RVチャンバの最も広い部分を通過するように配置されるべきである。 </li><li>このビューでは、RVの壁とIVSがはっきり見えるはずです。焦点深度がRV室の中心に位置していることを確認してください。測定のRVチャンバ寸法、FSおよびオフラインのRV壁の厚さのためにシネストアでデータを記録します。 Mモード画像の例を図2Cおよび2Dに示されている。 （6.3をご参照ください。） </li></ol> 2。ミッドの傍胸骨短軸部分的な区域の変更（FAC）を得た乳頭レベル<ol><li> （ 図1A）は、上記の位置から、Bモードに切り替えて、90°の胸骨傍短軸（ 図1B）を取得するために時計回りにプローブをオンにします。胸骨の閉塞を防止するために、図僅かにプローブのx軸に沿ってプローブを傾ける。 </li><li>ミッド乳頭レベルを得るために、プローブのy軸に沿ってわずかに上下に移動する（6.4をご参照ください。） </li><li>この図では、乳頭筋は、典型的には2と5時の位置（ 図3）に配置されている。 </li></ol> 3。大動脈弁レベル（RV PSAX大動脈レベル）の傍胸骨短軸がRV壁の厚さとPAピーク速度を取得する<ol><li>大動脈弁断面がウィンドウの中央に表示されるまで（ 図1B）は、上記の位置から、頭蓋骨に向かってY軸にプローブを移動します。 </li><li>右室流出TRACT（RVOT）は、 図4A及び2のBに示すように、三尖弁は、RAからRVを分離した三日月形の構造として一番上に表示されるはずです。オフラインのRV壁の厚さを測定するためにシネストアを使用してデータを記録します。 （6.5をご参照ください。） </li><li>同じ位置に留まる。 （6.6をご参照ください。） </li><li>カラードプラモードに切り替えて、容器内の流れの方向に黄色PW-破線に平行に配置します。青と赤の色が（ 図4Cおよび4のD）はそれぞれ、離れてから、プローブに向かって流れを示していることに注意してください。 </li><li>肺動脈弁尖の先端に、PWのカーソルを置きます。 （6.7をご参照ください。）シネストアを使用して記録データを。オフラインのPAピーク速度を測定します。 </li></ol> 4。ペンシルバニア州のピーク速度を取得するためにRVおよびPAの傍胸骨長軸の表示を変更した<ol><li> （MS550DまたはMS250プローブを配置し、Bモードの設定に継続）右胸骨傍のライン（ 図1C）、ゆっくりとタイトル図に示すように、明らかに大動脈上でのPA交差点を視覚化するマウスの胸に向けてプローブ（ 図1D）のy軸上のプローブ約30〜45°の角度に図5（a）および 5b。 </li><li>カラードプラモードに切り替えて、容器内の流れの方向（ 図5Cおよび5 D）への黄PW-破線に平行に配置します。肺動脈弁尖の先端に、PWのカーソルを置きます。シネストアを使用して記録データを（。6.6をご参照ください）​​とラインオフPAのピーク速度を測定。 </li></ol> 5。データ計算および分析<ol><li> RVの壁の厚さは（プロトコル3）上記のようにRV PSAX大動脈レベルから得られたBモードデータから計算することができる。 図6に、ピンクの領域に示すように（拡張期でRV壁の面積をトレースするツールをトレースする2次元エリアを選択）。すると、（ 図6の青線のように）RVOTの壁の内外周をトレースする距離のトレースツールを使用します。内外周の平均を取る。式を使用して<img fo:content-width="0.8in" src="/files/ftp_upload/51041/RVW_Thickness.jpg" width="80px" />我々は、RVの壁（RVW）の厚さを計算します。 （6.8をご参照ください。） </li><li>他の標準的なパラメータの場合は、それぞれのマニュアルを参照してくださいは、データ分析を実行するために製造しています。 </li></ol> 6。注釈<ol><li>すべての画像はVevoの2100システムを使用して収集されます。類似画像は、他のメーカーからの超音波イメージングシステムを用いて得ることができる、様々な超音波器具の相対的な長所と短所は、以前は8,12,15を比較した。それは、すべての画像が、可能な限り盲検様式で得られたし、分析することをお勧めします。 </li><li>このような短いdと麻酔の適切な選択、吸入イソフルラン（2-3％が誘導するために、1.0％を維持するために）のurationは、私たちが再現可能で一貫性の基礎と上昇し、肺動脈を検出することができるように、（500拍/分以上）、正常な生理レートで心拍の維持に不可欠である研究では収縮期血圧。 </li><li> （&gt; 200フレーム/秒）が可能、可能な限り高いフレームレートでデータを収集することを確認します。 </li><li>最大のチャンバ寸法を持つビューを探します。 </li><li>原因主にRVの胸骨の位置に肋骨と胸骨に障害物がRVを画像化するこの方法では良好な画像を得るための唯一最大の障害となっている。動物またはプローブを再配置することによって、オペレータは、胸骨のブロックを克服し、RVの必要なビューを取得することができます。これは、動物の生理機能に応じて、5〜15分かかる場合があり。 </li><li> MS550Dプローブは、PACの前に偽とマウスでは使用することができるためには、MS250にプローブを切り替える必要があり、40 MHzのプローブは、レコードにすることが可能です。300〜1,500メートル/秒のピーク速度、MS250が4000ミリメートル/秒の公園速度を捕捉することができるのに対し。 </li><li>それは、PAピーク速度を正確に測定するための20°未満プローブの角度を持つことが許容される。 </li><li> RV壁の厚さと面積/寸法の一貫性のある測定は、両方の長短軸に、複数の音響窓を用いて行った。これらのウィンドウのいくつかの選択は、作業者の経験に依存し、異なる統計結果に寄与する可能性の変動を説明できる。 </li></ol>

<ol>
	<li>Anavekar, N. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Usefulness+of+right+ventricular+fractional+area+change+to+predict+death,+heart+failure,+and+stroke+following+myocardial+infarction+(from+the+VALIANT+ECHO+Study).">Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study).</a> Am. J. Cardiol. 101, 607-612 (2008).</li><li>Berger, R. M., Cromme-Dijkhuis, A. H., Witsenburg, M., Hess, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tricuspid+valve+regurgitation+as+a+complication+of+pulmonary+balloon+valvuloplasty+or+transcatheter+closure+of+patent+ductus+arteriosus+in+children+&lt;+or+=+4+years+of+age.">Tricuspid valve regurgitation as a complication of pulmonary balloon valvuloplasty or transcatheter closure of patent ductus arteriosus in children &lt; or = 4 years of age.</a> Am. J. Cardiol. 72, 976-977 (1993).</li><li>Marwick, T. H., Raman, S. V., Carrio, I., Bax, J. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+developments+in+heart+failure+imaging.">Recent developments in heart failure imaging.</a> JACC Cardiovasc. Imaging. 3, 429-439 (2010).</li><li>Souders, C. A., Borg, T. K., Banerjee, I., Baudino, T. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pressure+overload+induces+early+morphological+changes+in+the+heart.">Pressure overload induces early morphological changes in the heart.</a> Am. J. Pathol. 181, 1226-1235 (2012).</li><li>Karas, M. G., Kizer, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiographic+assessment+of+the+right+ventricle+and+associated+hemodynamics.">Echocardiographic assessment of the right ventricle and associated hemodynamics.</a> Prog. Cardiovasc. Dis. 55, 144-160 (2012).</li><li>Lindqvist, P., Calcutteea, A., Henein, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiography+in+the+assessment+of+right+heart+function.">Echocardiography in the assessment of right heart function.</a> Eur. J. Echocardiogr. 9, 225-234 (2008).</li><li>Rudski, L. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+the+echocardiographic+assessment+of+the+right+heart+in+adults:+a+report+from+the+American+Society+of+Echocardiography+endorsed+by+the+European+Association+of+Echocardiography,+a+registered+branch+of+the+European+Society+of+Cardiology,+and+the+Canadian+Society+of+Echocardiography.">Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.</a> J. Am. Soc. Echocardiogr. 23, 685-713 (2010).</li><li>Scherrer-Crosbie, M., Thibault, H. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiography+in+translational+research:+of+mice+and+men.">Echocardiography in translational research: of mice and men.</a> J. Am. Soc. Echocardiogr. 21, 1083-1092 (2008).</li><li>Thibault, H. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+assessment+of+murine+pulmonary+arterial+pressure:+validation+and+application+to+models+of+pulmonary+hypertension.">Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension.</a> Circ. Cardiovasc. Imaging. 3, 157-163 (2010).</li><li>Polak, J. F., Holman, B. L., Wynne, J., Right Colucci, W. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ventricular+ejection+fraction:+an+indicator+of+increased+mortality+in+patients+with+congestive+heart+failure+associated+with+coronary+artery+disease.">ventricular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease.</a> J. Am. Coll. Cardiol. 2, 217-224 (1983).</li><li>Tanaka, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transthoracic+echocardiography+in+models+of+cardiac+disease+in+the+mouse.">Transthoracic echocardiography in models of cardiac disease in the mouse.</a> Circulation. 94, 1109-1117 (1996).</li><li>Benza, R., Biederman, R., Murali, S., Gupta, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+cardiac+magnetic+resonance+imaging+in+the+management+of+patients+with+pulmonary+arterial+hypertension.">Role of cardiac magnetic resonance imaging in the management of patients with pulmonary arterial hypertension.</a> J. Am. Coll. Cardiol. 52, 1683-1692 (2008).</li><li>Lang, R. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+chamber+quantification.">Recommendations for chamber quantification.</a> Eur. J. Echocardiogr. 7, 79-108 (2006).</li><li>Tarnavski, O., McMullen, J. R., Schinke, M., Nie, Q., Kong, S., Izumo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+cardiac+surgery:+comprehensive+techniques+for+the+generation+of+mouse+models+of+human+diseases+and+their+application+for+genomic+studies.">Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies.</a> Physiol. Genomics. 16, 349-360 (2004).</li><li>Schulz-Menger, , et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardized+image+interpretation+and+post+processing+in+cardiovascular+magnetic+resonance:+Society+for+Cardiovascular+Magnetic+Resonance+(SCMR)+Board+of+Trustees+Task+Force+on+Standardized+Post+Processing.">Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Post Processing.</a> J. Cardiovasc. Magn. Reson. 15, 35 (2013).</li><li>Williams, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+ultrasonic+measurement+of+regional+and+local+pulse-wave+velocity+in+mice.">Noninvasive ultrasonic measurement of regional and local pulse-wave velocity in mice.</a> Ultrasound Med. Biol. 33, 1368-1375 (2007).</li><li>Senechal, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+simple+Doppler+echocardiography+method+to+evaluate+pulmonary+capillary+wedge+pressure+in+patients+with+atrial+fibrillation.">A simple Doppler echocardiography method to evaluate pulmonary capillary wedge pressure in patients with atrial fibrillation.</a> Echocardiography. 25, 57-63 (2008).</li><li>Frea, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiographic+evaluation+of+right+ventricular+stroke+work+index+in+advanced+heart+failure:+a+new+index.">Echocardiographic evaluation of right ventricular stroke work index in advanced heart failure: a new index.</a> J. Card. Fail. 18, 886-893 (2012).</li><li>Pokreisz, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pressure+overload-induced+right+ventricular+dysfunction+and+remodelling+in+experimental+pulmonary+hypertension:+the+right+heart+revisited.">Pressure overload-induced right ventricular dysfunction and remodelling in experimental pulmonary hypertension: the right heart revisited.</a> Eur. Heart J. Suppl. , H75-H84 (2007).</li><li>Bauer, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Echocardiographic+speckle-tracking+based+strain+imaging+for+rapid+cardiovascular+phenotyping+in+mice.">Echocardiographic speckle-tracking based strain imaging for rapid cardiovascular phenotyping in mice.</a> Circ. Res. 108, 908-916 (2011).</li></ol>

開示することは何もありません。

我々は、TTEは、マウスにおいてRVの構造および機能のルーチン評価のための高感度で再現性のある方法を提供することを実証する。 TTEの到来前に、RVの研究は、主に右心カテーテル検査、端末と侵襲的手技6,9,11,17を通じてRVSP測定に焦点を当てた。 従来の報告は、右心3,4,11,17-19測定を行うための様々な技術を記載している。しかし、これまでの研?...

歴史的には、心不全の予後の評価は、心エコー検査を介してイメージしやすいLV、に焦点を当てている。心エコー検査を使用して左室の構造と機能に関する多くの研究は、LV構造のための正常値の設立につながったと1,5,6機能している。彼らはLV 7のための非常に詳細の区分およびジオメトリの視覚的な描写を可能にするように2次元およびカラードプラ画像から得たLVサイズと収縮機能の測定は非常に重要である。 Mモードは、しばしば、マウスにおいてLV寸法および短縮率（FS）を測定するために使用される。観察者間および観察者内の変動は、このモードを使用して、直径の測定のために低いが、壁厚の測定は、7非常に可変である傾向がある。色（PWまたはカラードプラ）でパルスドップラー弁逆流8,9を評価するために使用されています。 LVと同様に、RVが重要な役割を果たしており、有意なpである心肺疾患1,7,10に罹患した患者における罹患率および死亡率のredictor。しかし、RVの心エコー評価は、その複雑な形状5,11とその胸骨の位置8,9ブロック超音波と本質的に困難である。 RVは、LVの周りに三日月状の構造のラッピングされ、低圧および肺血管系6への耐性に慣れている薄い壁を持つ複雑な解剖学的構造を持っています。高架血管抵抗（PVR）を克服するために、RVがまず、サイズが大きくなり、肥大を受ける。肺高血圧症または肺血管疾患のような慢性疾患において、RVは最終的に収縮期および拡張期機能4,5,10の低下をもたらす、進行性の拡張を受ける。 心エコー検査は、その臨床診断能力に存在するいくつかの制限にもかかわらず、PAHのスクリーニングおよび診断に重要な役割を果たしている。の主な利点TTEは、それが非侵襲的であり、それは9で軽く鎮静させ、あるいは意識のある動物を上に行うことができる点である。 TTEはまた、PA圧力の合理的な見積りだけでなく、RVの構造と機能12,13の変化を継続的に評価しています。原因5〜12ミリメートル、高フレームレート（300フレーム/秒を超える）、および高サンプリングレートの深さ約50μmの距離分解能を可能に高周波機械的プローブの開発を含むTTEでの技術的な進歩が、これらに心エコー検査は急速に縮小し、小型マウス心臓8,11を画像化するための選択ツールです。 2次元（2D）短く、長軸、Mモードおよびドップラー音響ウィンドウを含む複数のビューを使用して、右室機能の長手方向の監視は、RVの解剖と機能の補完的な情報を提供します。総称して、この方法論は、生理学的および病理学的設定でのRV血行動態の完全な縦評価を可能にする<suP&gt; 4,7。 ここで、我々は、RVの解剖学的およびマウスでは、PACに対する二次的機能変化​​を特徴づけるために非侵襲TTEを使用しての詳細なステップバイステップの方法論を提供する。

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			<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

新興の臨床データは、右室機能不全は心血管疾患および心不全1-3の病因に重要であるという考えを支持している。また、RVが大幅な肺動脈高血圧症（PAH）などの肺疾患に影響を受けます。また、RVが左心室（LV）機能障害、弁膜症や右室梗塞4を含む心臓の病変、と非常に敏感である。心疾患の病因におけるRVの役割を理解するために、構造的および機能的にRVにアクセスするための信頼性の高い非侵襲的な方法が不可欠である。 非侵襲的な経胸腔心エコー（TTE）に基づく方法論が確立され、成体マウスでのRVの構造と機能の動的変化を監視するための検証されました。 RV応力を課すために、我々は、肺動脈狭窄（PAC）の外科的モデルを採用し、高周波数超音波マイクロイメージングを用いて7日間にわたってRV応答を測定システム。偽手術マウスを、対照として用いた。画像は（手術前）ベースライン時に軽く麻酔したマウスで取得し、0日目（手術直後）、3日目、7日目（術後）。データは、ソフトウェアを用いてオフラインで分析した。 一貫して、マウスで得られた（RV壁厚、拡張末期および収縮末期寸法を含む）RV構造の信頼性と再現性のある測定のために許可され、機能することができるいくつかの音響窓（B、M、およびカラードプラモード）、（部分的な区域の変更、短縮率、PAのピーク速度、ピーク圧力勾配）正常マウスとPAC以下。 この方法を使用して、PACから生じる圧力勾配を正確にカラードプラモードを使用してリアルタイムで測定し、ミラー高忠実度のマイクロチップカテーテルを用いて行わ直接圧力測定値と同等であった。まとめると、これらのデータは、様々なcomplをから得られた測定値RV心エコー検査を使用してimentaryビューは、信頼性の高い再現性とRVの構造と機能に関する洞察を提供することができます。この方法では、RVの心機能不全の役割をよりよく理解できるようになります。

本研究では、ベースライン心エコー検査は、手術前に48時間実施した。マウスを二つのグループに無作為化した。マウスは、肺動脈閉塞（PAC）および偽操作（偽手術）を受けた。心エコー検査は、外科的処置の翌日、0,3、および7で実施した。動物は、最後のエコー検査の直後に安楽死させ、心臓を組織学的評価のために回収した。カテーテル法は、サブグループ圧力カテーテルを介してRVSPを...

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

右心室（RV）機能障害は心血管疾患の病因に重要であり、まだ限られた方法論は、その評価のために用意されています。超音波画像診断の最近の進歩により、縦方向のRV研究のための非侵襲的かつ正確なオプションを提供しています。ここで、我々に詳細のRV圧負荷のマウスモデルを使用してステップバイステップの心エコー法。

経胸壁心エコー検査による肺動脈狭窄のマウスモデルにおける右室の構造と機能の評価

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

assessment-right-ventricular-structure-function-mouse-model-pulmonary

Research

JoVE Journal

Medicine

27.4K ビュー.  Harvard Medical School. 右心室（RV）機能障害は心血管疾患の病因に重要であり、まだ限られた方法論は、その評価のために用意されています。超音波画像診断の最近の進歩により、縦方向のRV研究のための非侵襲的かつ正確なオプションを提供しています。ここで、我々に詳細のRV圧負荷のマウスモデルを使用してステップバイステップの心エコー法。 

ビデオ: 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.

マウスにおける経胸壁心エコー

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

医学

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.

マウスの右心の心エコー評価

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.

慢性血栓塞栓性肺高血圧症とピグレットにおける右室機能の評価

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.

左心室心筋変形の定量的評価のための経胸壁スペックル追跡心エコー検査

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.

左心房、大動脈、肺動脈のマウス心エコー

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.

肺動脈バンディング圧負荷のモデルによる右室肥大と失敗

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.

ワイヤー図法を使用してマウスの腸間膜動脈の等尺性収縮力測定

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.

マウスにおける右心室系と低酸素誘発性肺動脈高血圧に対する侵襲的血行力学的評価

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.

3次元心エコー検査を用いた右心室の形態学的・機能的評価

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.

マウスにおける右冠動脈の永久結紮による右心室心筋梗塞の生成と特徴付け

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