XHTWは、医学研究でWMケック財団特別若い学者であり、そしてまた、NIH / NHLBIの助成金R01 - HL089598とR01 - R01HL091947、および筋ジストロフィー協会の助成金＃69238でサポートされています。 RJvOは生理ゲノミクスにおける2008年から2010年、アメリカ生理学会ポストドクトラルフェローシップの受賞者です。この作品は、CaMKIIはハートでシグナリングのための財団Leducqアライアンスによって部分的にサポートされています。

パート1：術野の準備<ol><li>動作フィールドは、75％イソプロピルアルコールで消毒されています。 </li><li>加熱パッドは上と右の温度でであることを確認してください。推奨されるシステムは、37℃で維持されている治療のパッドに接続されている水の循環ポンプGaymar℃± 1℃です。心拍数の急激な低下を避けるために手術中に正常な体温を維持することが重要です。 </li><li>手術器具は、手術前にホットビーズ滅菌器で滅菌されています。鈍はさみ、もちろん曲がったピンセットX 2、罰金45 °傾斜鉗子X 2、角度の春のはさみ、胸リトラクタ、およびニードルホルダー：この手順では、以下の手術器具が必要になります。 </li><li>コットンアプリケーターは、出血の場合には手にしてください。 </li></ol>パート2：マウスの​​調製と挿管<ol><li>マウスは0.5 -1.0 L /分100％O 2と混合イソフルラン2％の誘導室内で麻酔する。 </li><li>バリカンは、ネックラインからミッド胸の高さに毛を剃るために使用されます。 </li><li>マウスは、体温を維持するために加熱パッドの上仰臥位に配置されます。 </li><li>ゴムバンドを首を拡張するために動物の前歯の上に置かれる。片手で湾曲した鉗子を使用して、舌を優しく側に操作されます。一方で、気管内挿管はPE 90チューブを使用して実行されます。気管内チューブは、125〜150回/分および0.1〜0.3ミリリットルの一回換気量で、ハーバードのボリュームを再投入齧歯類の人工呼吸器のサイクリングに接続されています。 1.0 L /分100％O 2 -手術中、麻酔は0.5とイソフルラン1.5から2パーセントに維持されている。麻酔の適切なレベルは、マウスの爪床（つま先ピンチ反射）に圧力を適用することによって検証されます。 </li><li>手術野を70％アルコール、続いbetadine液で消毒されています。この手順を3回繰り返されます。 </li><li>運転中に手術野の汚染を防ぐために、滅菌ドレープは、操作フィールドが公開されたまま、マウスの上に配置されています。 </li><li>滅菌手袋のセットは、個々のマウスに使用されます。 </li></ol>パート3：横大動脈のライゲーション<ol><li>第二肋骨までの部分的開胸術は、手術用顕微鏡下で行われ、胸骨は胸のリトラクターを使用して、収納されています。 </li><li>ファイン先端45 °傾斜鉗子を穏やかに大動脈弓から胸腺と脂肪組織を分離するために使用されています。 </li><li>横大動脈の識別に続いて、6.0絹縫合糸の小片は、腕頭と左総頸動脈（図1）の間に配置されます。 </li><li>二つの緩い結び目が横大動脈と27の小片の周囲に関連付けられています½ゲージ鈍針が横大動脈に平行に配置されます。第一結び目はすぐに、針で引き分けた第二に続くと針は速やかに直径0.4mmの収縮を得るために削除されます。偽対照マウスでは、全体の手順は、大動脈のライゲーションを除いて同一です。 </li><li>胸のリトラクタが取り外され、再度膨らませる肺に2秒間人工呼吸器ピンチオフの流出された。 </li><li>胸郭は、結節縫合パターンを6.0 proleneの縫合糸を使用して閉じられます。 </li><li>皮膚は連続縫合パターンを6.0 proleneの縫合糸を使用して閉じられます。 </li></ol>パート4：手術後の回復<ol><li>術後鎮痛のために、マウスは、ブプレノルフィン（0.1 mg / kg）を腹腔内に注入されます。手術後の脱水の兆候がある場合は、滅菌生理食塩水を腹腔内に与えられます。 </li><li>麻酔が徐々にオフの位置に下げ、自発呼吸の兆候が発生したときに気管内チューブは削除されます。 </li><li>マウスは、発生しやすい位置に移動し、加熱パッドを回復するために許可されています。 </li></ol>第5部：横大動脈の成功ライゲーションの確認<ol><li> TAC 1週間後、マウスは横大動脈の結紮により誘発される圧負荷の程度を決定するために再麻酔です。上述したように、麻酔は0.5とイソフルラン1.5から2パーセントに維持されている- 37℃に維持1.0 L /分100％O 2と体温℃± 1℃の</li><li> 20 MHzのドップラープローブは、流速を検出するために45 °の角度で首の左右両側に配置されます。コンピュータベースのドップラー信号プロセッサ（インダスインスツルメンツ、ヒューストン、テキサス州）は、ドップラー信号を表示および格納するために使用されました5。 </li><li>実験的なプロトコルに必要な圧負荷の程度に応じて、一定の範囲内で右頸動脈（RC）/左頸動脈（LC）流量比を持つ唯一のマウスはさらなる分析のために含まれています。深刻な圧負荷を伴う厳密なくびれがtを導くのに対し、例えば、圧負荷中程度は、5-8の比率につながる8-10 OAの比（図5.3A）。シャム動物は（運営が連結していない）、しかし、〜1（図5.3B）の比率が期待される。 </li></ol> 6：代表的な結果野生型マウスでTACを以下の典型的な手術の生存率は約80〜90％です。横大動脈の手術が成功結紮は5-​​10の右と左総頸動脈との間のドップラー流速比（RC / LC）（図1）につながる。偽手術したマウス（図2A）と比較すると、圧負荷を持つマウスは、くびれの気密性（図2B）に応じて、6〜8週後1-2週間以内に心臓肥大、および心拡張を開発することが期待されています。遺伝子組み換えマウスは別の生存率を示すかもしれないがTACの後の最初の月の間に死亡率は、野生型マウスに（&lt;20％）一般的に低いです。6,7 <img src="/files/ftp_upload/1729/1729fig1tmb.jpg" alt="図1" border="0" /> 図1。ドップラー速度計測を用いて横大動脈ライゲーションの確認。右の代表ドップラー速度信号（RC）と左頸動脈（LC）動脈6日後のTAC。これらの録音は、〜6.8のRC / LC流量比で成功したライゲーションを示しています。してください<a href="https://jove.unicartagenaproxy.elogim.com/files/ftp_upload/1729/1729fig1.jpg">ここをクリックして</a>図1の拡大バージョンを参照すること。 <img src="/files/ftp_upload/1729/1729fig2.jpg" alt="図2" /> 図2。 TACに続いて代表的な心臓全体の画像。 。擬似手術野生型マウスの心臓。B。野生型マウスの心臓16週後のTAC。各ライン= 1ミリメートル。

<ol>
	<li>Rockman, H. A., Ross, R. S., Harris, A. N., Knowlton, K. U., Steinhelper, M. E., Field, L. J., Ross, J., Chein, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Segregation+of+atrial-specific+and+inducible+expression+of+an+atrial+natriuretic+factor+transgene+in+an+in+vivo+murine+model+of+cardiac+hypertrophy.">Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy.</a> Proc. Natl. Acad. Sci. USA. 88, 8277-8281 (1991).</li><li>Heineke, J., Molkentin, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regulation+of+cardiac+hypertrophy+by+intracellular+signaling+pathways.">Regulation of cardiac hypertrophy by intracellular signaling pathways.</a> Nat. Rev. Mol. Cell. Biol. 7, 589-600 (2006).</li><li>Hartley, C. J., Reddy, A. K., Madala, S., Michael, L. H., Entman, M. L., Taffett, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Doppler+estimation+of+reduced+coronary+flow+reserve+in+mice+with+pressure+overload+cardiac+hypertrophy.">Doppler estimation of reduced coronary flow reserve in mice with pressure overload cardiac hypertrophy.</a> Ultrasound Med. Biol. 34, 892-901 (2008).</li><li>Reddy, A. K., Taffett, G. E., Li, Y. -. H., Lim, S. -. W., Pham, T. T., Pocius, J. S., Entman, M. L., Michael, L. H., Hartley, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Doppler+signal+processing+for+use+in+mice:+applications.">Doppler signal processing for use in mice: applications.</a> IEEE Trans. Biomed. Eng. 52, 1771-1783 (2005).</li><li>Li, Y. -. H., Reddy, A. K., Ochoa, L. N., Pham, T. T., Hartley, C. J., Micheal, L. H., Entman, M. L., Taffett, G. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+age+on+peripheral+vascular+response+to+transverse+aortic+banding+in+mice.">Effect of age on peripheral vascular response to transverse aortic banding in mice.</a> J. Gerontol. 58A, 895-899 (2003).</li><li>Bourajjaj, M., Armand, A. S., Martins, d. a. C. o. s. t. a., Weijts, P. A., Nagel, B. V. a. n. d. e. r., Heeneman, R., Wehrens, S., Windt, X. H. D. e., J, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NFATc2+is+a+necessary+mediator+of+calcineurin-dependent+cardiac+hypertrophy+and+heart+failure.">NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure.</a> J. Biol. Chem. 28, 22295-22303 (2008).</li><li>Oort, R. J. v. a. n., Respress, J. L., Li, N., Reynolds, C., Almeida, A. C. D. e., Skapura, D. G., Windt, L. J. D. e., Wehrens, X. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Accelerated+development+of+pressure+overload+induced+cardiac+hypertrophy+and+dysfunction+in+an+RyR2-R176Q+knockin+mouse+model.">Accelerated development of pressure overload induced cardiac hypertrophy and dysfunction in an RyR2-R176Q knockin mouse model.</a> Hypertension. 55, (2010).</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></ol>

人間の大動脈弁狭窄症を模倣TACは、マウスでは心肥大や心不全を誘発することが一般的な方法です。大動脈狭窄のための代替サイトは、昇順および腹部大動脈が含まれています。大動脈狭窄を昇順とは、左心室（LV）上に極端な、より迅速な過負荷を提供します。対照的に、腹部大動脈狭窄は、可能な補償の手段として、循環の無傷の大部分を残します。従って8には、調査へのより?...

<table><tbody><tr><td>Gaymar T/pump</td><td>Harvard Apparatus</td><td>Model TP-500</td><td>Circulating water pump</td></tr><tr><td>Temp. therapy pads</td><td>Harvard Apparatus</td><td>60-3414</td><td></td></tr><tr><td>Hot bead sterilizer</td><td>Fine Science Tools</td><td>18000-45</td><td></td></tr><tr><td>Blunt scissors</td><td>Roboz Surgical Instruments Co.</td><td>RS-5980</td><td></td></tr><tr><td>Angled spring scissors</td><td>Roboz Surgical Instruments Co.</td><td>RS-5668</td><td></td></tr><tr><td>Chest retractor</td><td>Fine Science Tools</td><td>17002-02</td><td></td></tr><tr><td>Course curved forceps</td><td>Roboz Surgical Instruments Co.</td><td>RS-5138</td><td></td></tr><tr><td>Dumont fine 45&amp;#x00B0; angled forceps</td><td>Fine Science Tools</td><td>11253-25</td><td></td></tr><tr><td>Needle holder</td><td>Fine Science Tools</td><td>12565-14</td><td></td></tr><tr><td>Electric shaver</td><td>GE Healthcare</td><td></td><td>For shaving mouse fur</td></tr><tr><td>PE 90 tubing</td><td>BD Biosciences</td><td>427420</td><td>For intubation</td></tr><tr><td>MiniVent (ventilator)</td><td>Harvard Apparatus</td><td>Type 845</td><td></td></tr><tr><td>Betadine</td><td>Fisher Scientific</td><td>19-027132</td><td>May be purchased at medical supply store</td></tr><tr><td>Sterile gloves</td><td>Mckesson</td><td>20-1565</td><td></td></tr><tr><td>Stereo microscope</td><td>Unico</td><td>ZM186</td><td></td></tr><tr><td>6-0 silk suture</td><td>Fine Science Tools</td><td>18020-60</td><td></td></tr><tr><td>27 &amp;frac12; gauge needle</td><td>BD Biosciences</td><td>305109</td><td></td></tr><tr><td>6-0 prolene suture</td><td>Mckesson</td><td>3286</td><td></td></tr><tr><td>Buprenorphine</td><td>Institutional Animal Facility</td><td></td><td></td></tr></tbody></table>

transverse aortic constriction in mice

マウスの横大動脈狭窄（TAC）は、圧負荷誘発性心肥大および心不全のための一般的に使用される実験的なモデルです。<sup&gt; 1</sup&gt; TACは、最初は多くの場合、心臓の収縮性の一時的な強化に関連付けられている心臓、の補償肥大につながります。時間が経つにつれて、しかし、慢性的な血行動態の過負荷に対する応答は、心拡張と心不全の結果、不適応となります。<sup&gt; 2</sup&gt;マウスTACのモデルは、最初のロックマンによって検証された<em&gt;ら</em&gt;。<sup&gt; 1</sup&gt;、と以来、広く人間の心血管系疾患を模倣し、心臓肥大応答と心不全の開発に関わる基本的なシグナル伝達プロセスを解明する貴重なツールとして使用されています。このような左前下行（LAD）冠状動脈の完全閉塞などの心不全の他の実験モデル、と比較すると、TACは、心肥大や心不全の発症に、より緩やかな時間経過の再現性の高いモデルを提供します。ここで、我々はマウスに外科TACを実行するためにステップバイステップ手順を説明します。大動脈結紮によって生成圧負荷のレベルを決定するために、高い周波数ドップラープローブは、左右の頸動脈の血流速度との比率を測定するために使用されます。<sup&gt; 3、4</sup&gt; 80〜90％の手術の生存率では、バンディング横大動脈は、マウスの左室肥大や心不全を誘導する有効な手法です。

Watch this Scientific Journal Video about Transverse Aortic Constriction in Mice at JoVE.com

Transverse Aortic Constriction in Mice

マウスの横大動脈狭窄（TAC）は、心肥大や心不全の開発の基礎となるメカニズムを研究するために一般的に使用される実験的なモデルです。ここで、我々は、マウスの心肥大の再現性の学位を作成するために大動脈を収縮する手順を説明します。

マウスの横大動脈狭窄

Transverse aortic constriction (TAC) in the mouse is a commonly used experimental model for pressure overload-induced cardiac hypertrophy and heart ...

Universidad de Cartagena UDEC

Research

JoVE Journal

Biology

66.7K ビュー.  Baylor College of Medicine (BCM). マウスの横大動脈狭窄（TAC）は、心肥大や心不全の開発の基礎となるメカニズムを研究するために一般的に使用される実験的なモデルです。ここで、我々は、マウスの心肥大の再現性の学位を作成するために大動脈を収縮する手順を説明します。

ビデオ: Transverse Aortic Constriction in Mice

Heterotopic Heart Transplantation in Mice

The mouse heterotopic heart transplantation has been used widely since it was introduced by Drs. Corry and Russell in 1973. It is particularly valuable for studying rejection and immune response now that newer transgenic and gene knockout mice are available, and a large number of immunologic reagents have been developed. The heart transplant model is less stringent than the skin transplant models, although technically more challenging. We have developed a modified technique and have completed over 1000 successful cases of heterotopic heart transplantation in mice. When making anastomosis of the ascending aorta and abdominal aorta, two stay sutures are placed at the proximal and distal apexes of recipient abdominal aorta with the donor s ascending aorta, then using 11-0 suture for anastomosis on both side of aorta with continuing sutures. The stay sutures make the anastomosis easier and 11-0 is an ideal suture size to avoid bleeding and thrombosis.
When making anastomosis of pulmonary artery and inferior vena cava, two stay sutures are made at the proximal apex and distal apex of the recipient s inferior vena cava with the donor s pulmonary artery. The left wall of the inferior vena cava and donor s pulmonary artery is closed with continuing sutures in the inside of the inferior vena cava after, one knot with the proximal apex stay suture the right wall of the inferior vena cava and the donor s pulmonary artery are closed with continuing sutures outside the inferior vena cave with 10-0 sutures. This method is easier to perform because anastomosis is made just on the one side of the inferior vena cava and 10-0 sutures is the right size to avoid bleeding and thrombosis. In this article, we provide details of the technique to supplement the video.

The mouse heterotopic heart transplantation model has been proven by many investigators to be an important method for studying mechanisms of rejection and immune response. However, the techniques involved are still challenging. By modifying standard techniques we have had success with more than 1000 transplants.

マウスにおける異所心臓移植

The mouse heterotopic heart transplantation has been used widely since it was introduced by Drs. Corry and Russell in 1973. It is particularly valuable ...

生物学

Small Bowel Transplantation In Mice

Since 1990, the development of tacrolimus-based immunosuppression and improved surgical techniques, the increased array of potent immunosuppressive medications, infection prophylaxis, and suitable patient selection helped improve actuarial graft and patient survival rates for all types of intestine transplantation. Patients with irreversible intestinal failure and complications of parenteral nutrition should now be routinely considered for small intestine transplantation. However, Survival rates for small intestinal transplantation have been slow to improve compares increasingly favorably with renal, liver, heart and lung. The small bowel transplantation is still unsatisfactory compared with other organs. Further progress may depend on better understanding of immunology and physiology of the graft and can be greatly facilitated by animal models. A wider use of mouse small bowel transplantation model is needed in the study of immunology and physiology of the transplantation gut as well as efficient methods in diagnosing early rejection. However, this model is limited to use because the techniques involved is an extremely technically challenging. We have developed a modified technique. When making anastomosis of portal vein and inferior vena cava, two stay sutures are made at the proximal apex and distal apex of the recipient s inferior vena cava with the donor s portal vein. The left wall of the inferior vena cava and donor s portal vein is closed with continuing sutures in the inside of the inferior vena cava after, after one knot with the proximal apex stay suture the right wall of the inferior vena cava and the donor s portal vein are closed with continuing sutures outside the inferior vena cave with 10-0 sutures. This method is easier to perform because anastomosis is made just on the one side of the inferior vena cava and 10-0 sutures is the right size to avoid bleeding and thrombosis.  In this article, we provide details of the technique to supplement the video.

The mouse small bowel transplantation model has been recognized as an important tool to study mechanismes of immune rejection and screen new immunosuppressive drugs. However, this model is limited to use because the techniques involved is an extremely technically challenge. Now we introduce the modified technique.

マウスにおける小腸移植

Since 1990, the development of tacrolimus-based immunosuppression and improved surgical techniques, the increased array of potent immunosuppressive ...

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.

心臓形態学的および心エコーイメージングによって横大動脈狭窄のマウスモデルにおける機能の変更の評価

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

医学

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.

A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.

ラットの腹部大動脈の収縮を通じて心臓リモデリングのモデル

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Minimally Invasive Transverse Aortic Constriction in Mice

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.

Minimally invasive transverse aortic constriction (MTAC) conserves the essentials of regular transverse aortic constriction (TAC) while eliminating the use of a ventilator with tracheal intubation. It proves to be a highly desirable method for high-throughput studies on left ventricular overload, particularly in translational studies.

マウスにおける低侵襲横大動脈狭窄

Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard ...

Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure overload-induced left ventricular hypertrophy (LVH) and its progression to heart failure. In the majority of the reported investigations, this procedure is performed with intubation and ventilation of the animal which renders it demanding and time-consuming and adds to the surgical burden to the animal. The aim of this protocol is to describe a simplified technique of minimally invasive TAC without intubation and ventilation of mice. Critical steps of the technique are emphasized in order to achieve low mortality and high efficiency in inducing LVH.
Male C57BL/6 mice (10-week-old, 25-30 g, n=60) were anesthetized with a single intraperitoneal injection of a mixture of ketamine and xylazine. In a spontaneously breathing animal following a 3-4 mm upper partial sternotomy, a segment of 6/0 silk suture threaded through the eye of a ligation aid was passed under the aortic arch and tied over a blunted 27-gauge needle. Sham-operated animals underwent the same surgical preparation but without aortic constriction. The efficacy of the procedure in inducing LVH is attested by a significant increase in the heart/body weight ratio. This ratio is obtained at days 3, 7, 14 and 28 after surgery (n = 6 - 10 in each group and each time point). Using our technique, LVH is observed in TAC compared to sham animals from day 7 through day 28. Operative and late (over 28 days) mortalities are both very low at 1.7%.
In conclusion, our cost-effective technique of minimally invasive TAC in mice carries very low operative and post-operative mortalities and is highly efficient in inducing LVH. It simplifies the operative procedure and reduces the strain put on the animal. It can be easily performed by following the critical steps described in this protocol.

The aim of this protocol is to describe step-by-step the technique of minimally invasive transverse aortic constriction (TAC) in mice. By elimination of intubation and ventilation which are mandatory for the commonly used standard procedure, minimally invasive TAC simplifies the operative procedure and reduces the strain put on the animal.

左室肥大の誘導マウスにおける低侵襲の横大動脈狭窄のテクニック

Transverse aortic constriction (TAC) in mice is one of the most commonly used surgical techniques for experimental investigation of pressure ...

A Closed-chest Model to Induce Transverse Aortic Constriction in Mice

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to perform a partial thoracotomy to visualize the transverse aortic arch. However, the surgical trauma caused by the thoracotomy in open-chest models changes the respiratory physiology as the ribs are dissected and left unattached after chest closure. To prevent this, we established a minimally invasive, closed chest approach via lateral thoracotomy. Herein we approach the aortic arch via the 2nd intercostal space without entering the chest cavities, leaving the mouse with a less traumatic injury to recover from. We perform this operation using standard laboratory settings for open chest TAC procedures with equal survival rates. Apart from maintaining physiological breathing patterns due to the closed chest approach, the mice seem to benefit by showing rapid recovery, as the less invasive technique appears to facilitate a fast healing process and to reduce immune response after trauma.

Here, we present a protocol of Transverse Aortic constriction (TAC) via a lateral thoracotomy. This technique is a minimally invasive, closed chest surgical procedure aiming to simulate pressure overload and heart failure in mice utilizing standard TAC laboratory settings.

マウスで横方向の大動脈狭窄を誘導するために閉じて胸モデル

Research on cardiac hypertrophy and heart failure is frequently based on pressure overload mouse models induced by TAC. The standard procedure is to ...

Operating Transverse Aortic Constriction with Absorbable Suture to Obtain Transient Myocardial Hypertrophy

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate cardiomyocyte hypertrophy and slow down progression to heart failure. For novices, however, the MHP model is usually quite difficult to establish because of the technical obstacles in ventilator operation, opening the chest repeatedly, and bleeding caused by debanding. To facilitate this model, to increase the surgical success rate and to reduce the incidence of bleeding, we switched to absorbable sutures for the first TAC combing with a ventilator-free technique. Using a 2-week absorbable suture, we demonstrated that this procedure could cause significant myocardial hypertrophy in 2 weeks; and 4 weeks after surgery, myocardial hypertrophy was almost completely regressed to the baseline. Using this protocol, the operators could master the MHP model easily with a lower operation mortality.

This protocol presents an improved method to obtain transient myocardial hypertrophy with absorbable suture, simulating left ventricular hypertrophy decrease after removing pressure overload. It could be valuable for the studies on myocardial hypertrophic preconditioning.

過渡性心筋肥大を得るために吸収性縫合を用いて横方向の大動脈収縮を操作する

Based on twice transverse aortic constrictions (TACs) in mice, it is proved that myocardial hypertrophic preconditioning (MHP) could attenuate ...

A Modified Technique for Transverse Aortic Constriction in Mice

Transverse aortic constriction (TAC) is a frequently used surgery in research regarding heart failure and cardiac hypertrophy based on the formation of pressure overload in mouse models. The main challenge of this procedure is to clearly visualize the transverse aortic arch and precisely band the target vessel. Classical approaches perform a partial thoracotomy to expose the transverse aortic arch. However, it is an open-chest model that causes a rather large surgical trauma and requires a ventilator during the surgery. To prevent unnecessary trauma and simplify the operating procedure, the aortic arch is approached via the proximal proportion of the sternum, reaching and binding the target vessel using a small self-made retractor that contains a snare. This procedure can be conducted without entering the pleura cavity and does not need a ventilator or microsurgical operation, which leaves the mice with physiological breathing patterns, simplifies the procedure, and significantly reduces operation time. Due to the less invasive approach and less operation time, mice can undergo fewer stress reactions and recover rapidly.

The present protocol describes a modified and simplified technique with a minimally invasive transverse aortic constriction (TAC) procedure using a self-made retractor. This procedure can be conducted without a ventilator or microscope and introduces pressure overload, eventually leading to cardiac hypertrophy or heart failure.

マウスにおける横行大動脈狭窄の修正技術

Transverse aortic constriction (TAC) is a frequently used surgery in research regarding heart failure and cardiac hypertrophy based on the formation of ...

Transverse Aortic Arch Banding in Mouse Model: A Minimally Invasive Technique in Mice for Induction of High Pressure in the Left Ventricle

Source: Zaw, A. M. et al. <a href="https://jove.unicartagenaproxy.elogim.com/video/55293" target="_blank">Minimally Invasive Transverse Aortic Constriction in Mice</a>. J. Vis. Exp. (2017)
In this video, we demonstrate an experimental protocol for minimally invasive transverse aortic constriction in mice to examine pressure overload-induced heart failure.

マウスモデルにおける横方向大動脈弓バンディング:左心室における高圧誘導のためのマウスにおける低侵襲技術

Source: Zaw, A. M. et al. Minimally Invasive Transverse Aortic Constriction in Mice. J. Vis. Exp. (2017)
In this video, we demonstrate an experimental ...