1。プロトコルテキスト<ol><li>手術に進む前に、6週齢または2から5パーセント、イソフルランの吸入による古けれ雄マウス（C57BL / 6）を麻酔。動物が十分に麻酔であることを確認するためにつま先のピンチを実行します。 </li><li>無意識のマウスは37℃の一定温度を維持するために暖かいパッドの上に仰向けに置かれ左側胸部胸部を剃毛されています。 </li><li>イソフルラン充填室で挿管デバイスにマウスを固定します。口からマウスの気管内に0.2内径のチューブを挿入し、無菌手術領域（37℃温度調節器によって）挿管にマウスを置いて、人工呼吸器（分あたり120のレートの圧力に気管内チューブを接続4月6日MMH 2 O）は、ベタジンと75％エタノールで領域を消毒。 </li><li>マウスの目に眼軟膏を適用します。足で標準のECG電極を置き、心電図レコーダーにマウスを接続します。 </li&gt; <li>半ば腋窩線に沿って1.5センチメートル切開を作るために滅菌ハサミを使用します。はさみは、マウスにおける皮下組織への損傷を避けるために、メスではなく、使用されています。その後、胸壁から前胸部の筋肉を切開し、撤回するブラントチップ容器はさみを使用しています。 </li><li>心臓と左肺の前方表面を可視化するために、第3および第4肋骨の間の左開胸を行います</li><li>さらに可視化とアクセシビリティを向上させるために、適切なリトラクターを使用して胸壁を撤回。歯鉗子、鈍先端がハサミを使って、心膜を取り除きます。 </li><li>リガチャーと動脈の間に心筋のバンドと一緒に動脈の下に針を（7-0 ethilon縫合糸で添付）を配置することにより、左冠動脈を結紮する。冠状動脈の閉塞に成功し、前方左心室壁のhypokinesis /無動でと心電図記録（ 例えば、ST上昇、QRS broadeniの変化によって確認されNG） </li><li> 3番目と4番目のリブ上に2つのステッチを（6-0 ethilon縫合）を配置することにより、胸を閉じます。 </li><li>皮膚を閉じるために5から0 ethilon縫合糸を使用しています。 </li><li>術後鎮痛のために、ブプレノルフィン（0.05 mg / kg）の単回腹腔内注射を投与。動物が自発的にイソフルラン麻酔を停止した後に2から5分以内に回復します。最後に、暖かいケージにマウスを置き、飲料水（テキストオーバーレイ：飲料水に0.6 mg / ml）の中のブプレノルフィン0.6 mg / mlのを提供し、術後の苦痛を防止する。密接に手術後の最初の24時間のためにマウスを監視します。 </li><li>心エコー検査は、3日心筋梗塞後の心機能を評価するために実施されています。成功した手順は、前方左心室壁における無動（結果で囲んでビデオを参照）によって検証されます。実験終了時に、心がさらなる調査のために、80℃に収 ​​集され保存されます。 すなわち遺伝子発現が。 </li></ol>

<ol>
	<li>Tabrizchi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Beta-blocker+therapy+after+acute+myocardial+infarction.">Beta-blocker therapy after acute myocardial infarction.</a> Expert Rev. Cardiovasc. Ther. 11, 293-296 (2013).</li><li>Pell, S., Fayerweather, W. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trends+in+the+incidence+of+myocardial+infarction+and+in+associated+mortality+and+morbidity+in+a+large+employed+population,+1957-1983.">Trends in the incidence of myocardial infarction and in associated mortality and morbidity in a large employed population, 1957-1983.</a> N. Engl. J. Med. 312, 1005-1011 (1985).</li><li>Ramunddal, T., Gizurarson, S., Lorentzon, M., Omerovic, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiarrhythmic+effects+of+growth+hormone--in+vivo+evidence+from+small-animal+models+of+acute+myocardial+infarction+and+invasive+electrophysiology.">Antiarrhythmic effects of growth hormone--in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology.</a> J. Electrocardiol. 41, 144-151 (2008).</li><li>Thom, T., Haase, N., Rosamond, W., Howard, V. J., Rumsfeld, J., Manolio, T., Zheng, Z. J., Flegal, K., O'Donnell, C., Kittner, 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=Heart+disease+and+stroke+statistics--2006+update:+A+report+from+the+american+heart+association+statistics+committee+and+stroke+statistics+subcommittee.">Heart disease and stroke statistics--2006 update: A report from the american heart association statistics committee and stroke statistics subcommittee.</a> Circulation. 113, 85-151 (2006).</li><li>van den Bos, E. J., Mees, B. M., de Waard, M. C., de Crom, R., Duncker, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+model+of+cryoinjury-induced+myocardial+infarction+in+the+mouse:+A+comparison+with+coronary+artery+ligation.">A novel model of cryoinjury-induced myocardial infarction in the mouse: A comparison with coronary artery ligation.</a> Am. J. Physiol. Heart Circ. Physiol. 289, 1291-1300 (2005).</li><li>Omerovic, E., Ramunddal, T., Lorentzon, M., Nordlander, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+neuropeptide+y2+receptor+blockade+on+ventricular+arrhythmias+in+rats+with+acute+myocardial+infarction.">Effects of neuropeptide y2 receptor blockade on ventricular arrhythmias in rats with acute myocardial infarction.</a> Eur. J. Pharmacol. 565, 138-143 (2007).</li><li>Ahn, D., Cheng, L., Moon, C., Spurgeon, H., Lakatta, E. G., Talan, M. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Induction+of+myocardial+infarcts+of+a+predictable+size+and+location+by+branch+pattern+probability-assisted+coronary+ligation+in+c57bl/6+mice.">Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in c57bl/6 mice.</a> Am. J. Physiol. Heart Circ. Physiol. 286, 1201-1207 (2004).</li><li>Lindbom, M., Ramunddal, T., Camejo, G., Waagstein, F., Omerovic, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+effects+of+myocardial+creatine+depletion+on+left+ventricular+function+morphology+and+lipid+metabolism:+Study+in+a+mouse+model.">In vivo effects of myocardial creatine depletion on left ventricular function morphology and lipid metabolism: Study in a mouse model.</a> J. Card Fail. 14, 161-166 (2008).</li><li>Omerovic, E., Bollano, E., Basetti, M., Kujacic, V., Waagstein, L., Hjalmarson, A., Waagstein, F., Soussi, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bioenergetic,+functional+and+morphological+consequences+of+postinfarct+cardiac+remodeling+in+the+rat.">Bioenergetic, functional and morphological consequences of postinfarct cardiac remodeling in the rat.</a> J. Mol. Cell. Cardiol. 31, 1685-1695 (1999).</li><li>Gao, E., Lei, Y. H., Shang, X., Huang, Z. M., Zuo, L., Boucher, M., Fan, Q., Chuprun, J. K., Ma, X. L., Koch, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+and+efficient+model+of+coronary+artery+ligation+and+myocardial+infarction+in+the+mouse.">A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse.</a> Circ. Res. 107, 1445-1453 (2010).</li></ol>

特別な利害関係は宣言されません。

本報告書で示したように、LCA結紮のため外科的処置は、マウス3,6の実験的心筋梗塞の誘導のための信頼性と再現性の高い方法です。このプロトコルに従ってLCAのライゲーションは、典型的には魅力的心筋虚血を誘発〜左心室3の40％。これは、心臓の前面にST部分7と可視蒼白の大幅な心電図変化を誘導する。大心筋梗塞が原因で、死亡率は30％まで8,9にすること...

modified technique for coronary artery ligation in mice

心筋梗塞（MI）は、1月3日 、人間の死亡率の最も重要な原因の一つである。心筋梗塞患者において罹患率と死亡率を改善するために我々は、心筋虚血の病態生理についてのよりよい知識を必要としています。この知識は、4革新的な心血管治療のための新しい治療標的を定義することは貴重であるかもしれません。マウスの実験ミシガンモデルはMIは左冠動脈（LCA）の5の永続的または一時的なライゲーションによって誘発された臨床研究でますます人気の小動物モデルである。このビデオでは、マウスで実験的心筋梗塞を誘発する方法をステップバイステップ方法について説明します。 動物は2％イソフルランを持つ最初の麻酔です。無意識のマウスは、その後挿管と人工換気のために人工呼吸器に接続されています。左胸を剃毛され、半ば腋窩線に沿って1.5センチメートル切開を皮膚で作られています。左大胸筋はぶっきらぼうdissocです肋骨が露出するまでiated。筋層はさておき引っ張って瞼リトラクタと固定されています。これらの準備の後、左開胸心臓と左肺の前表面を可視化するために、3番目と4番目のリブの間で行われます。 LCAの動脈の近位のセグメントは、一般的に梗塞サイズ〜左心室の40％を誘発7から0 ethilon縫合糸で結紮する。終了時には、胸が閉じられ、動物（Temgesic、0.3 mg/50ミリリットル、ip）を術後鎮痛法を受けています。動物は自然回復するまで暖かいケージ内に保持されます。

<html><table border="1" ><tbody><tr><td> 楽器 </td><td> 関数の説明 </td></tr><tr><td>ブラントチップはさみ</td><td>皮膚、肋間胸筋、および縫合糸を切断するために使用</td></tr><tr><td>アイ·リトラクター</td><td>外科ビューを公開するために使用</td></tr><tr><td>ブラントチップ鉗子</td><td>皮膚や筋肉を把握するために使用</td></tr><tr><td>ニードルホルダー</td><td>針を保持するには</td></tr><tr><td> 5から0縫合</td><td...

Watch this Scientific Journal Video about Modified Technique for Coronary Artery Ligation in Mice at JoVE.com

Modified Technique for Coronary Artery Ligation in Mice

マウスにおける実験的心筋梗塞を誘発するために用いる外科手術は、心臓や肺の左前方の表面を可視化するために、3番目と4番目のリブの間に左開胸で始まります。左冠動脈を結紮され、胸が閉じているとマウスが自発的に回復させる。

マウスにおける冠動脈結紮のために修飾されたテクニック

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

modified-technique-for-coronary-artery-ligation-in-mice

Research

JoVE Journal

Medicine

25.5K ビュー.  Sahlgrenska Academy, University of Gothenburg. マウスにおける実験的心筋梗塞を誘発するために用いる外科手術は、心臓や肺の左前方の表面を可視化するために、3番目と4番目のリブの間に左開胸で始まります。左冠動脈を結紮され、胸が閉じているとマウスが自発的に回復させる。

ビデオ: Modified Technique for Coronary Artery Ligation in Mice

Use of a Hanging Weight System for Coronary Artery Occlusion in Mice

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available 1-38. Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of knockout mouse studies is particularly important 7, 14, 30, 39. Despite the fact that previous studies have already successfully performed cardiac ischemia and reperfusion in mice, this model is technically very challenging. Particularly, visual identification of the coronary artery, placement of the suture around the vessel and coronary occlusion by tying off the vessel with a supported knot is technically difficult. In addition, re-opening the knot for intermittent reperfusion of the coronary artery during IP without causing surgical trauma adds additional challenge. Moreover, if the knot is not tied down strong enough, inadvertent reperfusion due to imperfect occlusion of the coronary may affect the results. In fact, this can easily occur due to the movement of the beating heart.
Based on potential problems associated with using a knotted coronary occlusion system, we adopted a previously published model of chronic cardiomyopathy based on a hanging weight system for intermittent coronary artery occlusion during IP 39. In fact, coronary artery occlusion can thus be achieved without having to occlude the coronary by a knot. Moreover, reperfusion of the vessel can be easily achieved by supporting the hanging weights which are in a remote localization from cardiac tissues.
We tested this system systematically, including variation of ischemia and reperfusion times, preconditioning regiments, body temperature and genetic backgrounds39. In addition to infarct staining, we tested cardiac troponin I (cTnI)
as a marker of myocardial infarction in this model. In fact, plasma levels of cTnI correlated with infarct sizes (R2=0.8). Finally, we could show in several studies that this technique yields highly reproducible infarct sizes during murine IP and myocardial infarction6, 8, 30, 40, 41. Therefore, this technique may be helpful for researchers who pursue molecular mechanisms involved in cardioprotection by IP using a genetic approach in mice with targeted gene deletion. Further studies on cardiac IP using transgenic mice may consider this technique.

A murine model for myocardial ischemia and ischemic preconditioning is an important tool study cardioprotective mechanisms in vivo. Here, we report an easy applicable in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion.

マウスにおける冠動脈閉塞のために掛かる重量のシステムの使用

Murine studies of acute injury are an area of intense investigation, as knockout mice for different genes are becoming increasingly available 1-38. ...

医学

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

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

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

心筋梗塞のマウスモデルにおける冠動脈結紮および心筋内注入

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo.  With the advent of genetic modifications to ...

The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to develop suitable animal models to study the events that unfold during ischemic insult. These techniques include transient or permanent, focal or global ischemia models using many different animal models, with the most common being rodents.
The permanent MCA ligation method which is also referred as pMCAo in the literature is used extensively as a focal ischemia model in rodents 1-6. This method was originally described for rats by Tamura et al. in 1981 7. In this protocol a craniotomy was used to access the MCA and the proximal regions were occluded by electrocoagulation. The infarcts involve mostly cortical and sometimes striatal regions depending on the location of the occlusion. This technique is now well established and used in many laboratories 8-13. Early use of this technique led to the definition and description of &#x201C;infarct core&#x201D; and &#x201C;penumbra&#x201D; 14-16, and it is often used to evaluate potential neuroprotective compounds 10, 12, 13, 17. Although the initial studies were performed in rats, permanent MCA ligation has been used successfully in mice with slight modifications 18-20 .
This model yields reproducible infarcts and increased post-survival rates. Approximately 80% of the ischemic strokes in humans happen in the MCA area 21 and thus this is a very relevant model for stroke studies. Currently, there is a paucity of effective treatments available to stroke patients, and thus there is a need for good models to test potential pharmacological compounds and evaluate physiological outcomes. This method can also be used for studying intracellular hypoxia response mechanisms in vivo. 
Here, we present the MCA ligation surgery in a C57/BL6 mouse. We describe the pre-surgical preparation, MCA ligation surgery and 2,3,5 Triphenyltetrazolium chloride (TTC) staining for quantification of infarct volumes.

Middle cerebral artery (MCA) ligation is a technique to study focal cerebral ischemia in animal models. In this method, the middle cerebral artery is exposed by craniotomy and ligated by cauterization. This method gives highly reproducible infarct volumes and increased post-operative survival rates compared to other methods available.

マウスの永久中大脳動脈結紮の応用

Focal cerebral ischemia is among the most common type of stroke seen in patients. Due to the clinical significance there has been a prolonged effort to ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

マウスにおけるタキサンの薬物動態学的および薬力学的分析のための頸動脈煎茶

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

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

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure.
Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling.
Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.

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

マウスの左前下冠動脈の動脈の常設ライゲーション：心筋梗塞後のリモデリングおよび心不全のモデル

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

Ultrasound Based Assessment of Coronary Artery Flow and Coronary Flow Reserve Using the Pressure Overload Model in Mice

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow reserve (CFR) in humans. Reduced CFR is accompanied by marked intramyocardial and pericoronary fibrosis and is used as an indication of the severity of dysfunction. This study explores, step-by-step, the real-time changes measured in the coronary flow velocity, CFR and systolic to diastolic peak velocity (S/D) ratio in the setting of an aortic banding model in mice. By using a Doppler transthoracic imaging technique that yields reproducible and reliable data, the method assesses changes in flow in the septal coronary artery (SCA), for a period of over two weeks in mice, that previously either underwent aortic banding or thoracotomy. 
During imaging, hyperemia in all mice was induced by isoflurane, an anesthetic that increased coronary flow velocity when compared with resting flow. All images were acquired by a single imager. Two ratios, (1) CFR, the ratio between hyperemic and baseline flow velocities, and (2) systolic (S) to diastolic (D) flow were determined, using a proprietary software and by two independent observers. Importantly, the observed changes in coronary flow preceded LV dysfunction as evidenced by normal LV mass and fractional shortening (FS). 
The method was benchmarked against the current gold standard of coronary assessment, histopathology. The latter technique showed clear pathologic changes in the coronary artery in the form of peri-coronary fibrosis that correlated to the flow changes as assessed by echocardiography. 
The study underscores the value of using a non-invasive technique to monitor coronary circulation in mouse hearts. The method minimizes redundant use of research animals and demonstrates that advanced ultrasound-based indices, such as CFR and S/D ratios, can serve as viable diagnostic tools in a variety of investigational protocols including drug studies and the study of genetically modified strains.

Coronary flow reserve (CFR) is useful for assessment of myocardial oxygen demand and evaluation of cardiovascular risk. This study establishes a step-by-step transthoracic Doppler echocardiographic (TTDE) method for longitudinal monitoring of the changes in CFR, as measured from coronary artery in mice, under the experimental pressure overload of aortic banding.

マウスの圧負荷モデルを用いた冠動脈の流れと冠血流準備の超音波ベースのアセスメント

Transthoracic Doppler echocardiography (TTDE) is a clinically useful, noninvasive tool for studying coronary artery flow velocity and coronary flow ...

Murine Left Anterior Descending (LAD) Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by reduced blood supply to the heart, resulting in the loss of oxygen to and the ensuing necrosis of the heart muscle. The MI model has gained popularity for its use as a short-term ischemia-reperfusion model and a long-term permanent ligation model. Below, we describe a reliable method for the permanent ligation of the LAD. With mouse genetic engineering technology becoming more advanced, and with an increasing availability of quality murine surgical instruments, the mouse has become a popular model for MI surgeries. Our surgical model incorporates the use of an easily reversible anesthetic for the rapid recovery of the mouse; a minimally invasive endotracheal intubation without involving a tracheotomy; and a thoracentesis through the original thoracotomy site without creating an additional incision in the chest, as is done in some other methods, to effectively remove excess blood and air from the chest cavity. This method is comparatively less invasive than other methods, which dramatically reduces surgical and post-surgical complications and mortality and improves reproducibility.

Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction

We provide a reliable method for left anterior descending artery (LAD) ligation in a mouse model. This method is comparatively less invasive than other methods, involving endotracheal intubation, a left-sided thoracotomy approach, and thoracentesis. This method can be used as a model for both acute and chronic myocardial infarction (MI).

マウス左前方降順（LAD）冠動脈結紮：心筋梗塞のための改善と簡略化されたモデル

Ischemic heart disease (IHD), or acute coronary syndrome (ACS), is one of the leading causes of death in the United States. IHD is characterized by ...

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA)

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ischemia and infarction in children. If left untreated, it results in a 90% mortality rate in the first year of life. In patients who survive to the adulthood, the coronary steal phenomenon and retrograde left-sided coronary flow provide a substrate for chronic subendocardial ischemia, which may lead to left ventricular dysfunction, ischemic mitral regurgitation, malignant ventricular arrhythmias, and sudden cardiac death. The average age of life-threatening presentation is 33 years and of sudden cardiac death 31 years. Therefore, surgical correction is highly recommended as soon as the diagnosis is made, regardless of age. In adult-type ALCAPA originating from the right-facing sinus of the pulmonary artery, direct re-implantation of the ALCAPA into the aorta is the more physiologically sound repair technique to re-establish the dual-coronary perfusion system and is recommended. This protocol describes the technique of direct re-implantation of adult-type ALCAPA into the aorta.

Direct Re-implantation of Left Coronary Artery into the Aorta in Adults with Anomalous Origin of Left Coronary Artery from the Pulmonary Artery ALCAPA

Surgical correction of ALCAPA is highly recommended, regardless of age or the degree of intercoronary collateralization. This protocol presents a technique for the direct re-implantation of adult-type ALCAPA into the aorta to re-establish the dual-coronary perfusion. Whenever feasible, direct re-implantation is preferred to other surgical correction techniques.

肺動脈から左冠状動脈の異常原点と成人における大動脈内に左冠状動脈の直接再注入（ALCAPA）

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly which is one of leading causes of myocardial ...

Identifying Coronary Artery Calcification on Non-gated Computed Tomography Scans

Coronary artery calcification (CAC) provides an objective measure of coronary artery disease and can readily be identified on non-gated computed tomography (CT) scans with a high correlation with gated cardiac CT scans. This standardized protocol takes a step-wise approach to not only optimizing an image for the identification of calcification but also to distinguishing CAC from other common causes of calcification in the cardiac silhouette. Recognition of CAC on non-gated CT scans helps to identify a very powerful prognostic factor that can influence therapeutic interventions or downstream diagnostic testing without requiring a gated cardiac scan. These non-gated CT scans are often acquired as part of the routine care of the patient, and this data is readily available without another dose of&#160;ionizing radiation. This protocol allows for the precise and accurate extraction of this data for the purposes of retrospective data analysis in clinical research studies, but also in the clinical evaluation and management of patients.

Here, we present a protocol to reliably and systematically identify coronary artery calcification (CAC) on non-gated computed tomography (CT) scans of the chest or abdomen. CAC provides an objective measure of coronary artery disease for both research and clinical purposes.

断層レントゲン写真撮影スキャンを計算非ゲートの冠動脈石灰化を識別します。

Coronary artery calcification (CAC) provides an objective measure of coronary artery disease and can readily be identified on non-gated computed ...

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine models of MI with permanent ligation of left-anterior descending (LAD) coronary artery closely mimics MI in humans. Murine models benefit from the extensive genetic engineering available nowadays. Here we propose a reproducible murine surgical model of myocardial infarction by permanent LAD coronary ligation. Our technique comprises anesthesia with ketamine/xylazine that can be rapidly reversed by administration of an antagonist, intubation without tracheotomy for mechanical-assisted ventilation, ventilation with application of extrinsic positive end-expiratory pressure (PEEP) to avoid alveolar collapse, a thoracotomy method limiting to the minimum surgical lesions made to skeletal muscles, and lung inflation without thoracentesis. This method is sparsely invasive, reproducible and reduces post-surgery mortality and complications.

Herein we describe a surgical procedure showing how to achieve permanent ligation of the left-anterior descending coronary artery in mice. This model is of high relevance to investigate the pathophysiology of myocardial infarction and the concomitant biological processes.

左前皮下冠動脈の永久的なライゲーションを用いたマウス心筋梗塞モデル

Myocardial infarction (MI) and acute coronary diseases are among the most prominent causes of death in population with western lifestyle. The murine ...