This project is supported in part by grant KKF-15-1.

注：冠動脈内アセチルコリン試験は地域倫理委員会によって承認されているプロトコルは、人間の研究のための私たちの機関のガイドラインに従います。 アセチルコリン溶液の調製（材料表を参照してください） <ol><li>パッケージに付属している溶剤2mlで20mgのアセチルコリンを混ぜます。 </li><li> NaCl、0.9％の98ミリリットルの2ミリリットルACHのソリューションを追加します。これは、ミリリットルの0.2mg /用量に対応し、NaClを91ミリリットルに0.9％を原液1の9ミリリットルを加え原液1と呼ばれ、これはミリリットル18μgの/の投与量に相当し、原液2と呼ばれています。 </li><li> 「高」、「中」、「低」とラベルされた3潅流シリンジ（50ミリリットルの各）を準備します。原液2 40mlで「ハイ」と表示された灌流シリンジ1を入力します。 </li><li>灌流シリンジ1（高）の8ミリリットルで灌流シリンジ2（ラベル「中」）を記入し、NaClを0.9％の32ミリリットルを追加します。これはに対応します3.6 / mlの用量。 </li><li>灌流シリンジ2（中）4mlで（「低」のラベル）灌流シリンジ3を記入し、NaClを0.9％の36ミリリットルを追加します。これは、0.36μgの/ mlの用量に相当します。 </li></ol>アセチルコリンの冠動脈内注射用シリンジの調製<ol><li>冠動脈内注入のための5シリンジ（5ミリリットルの4シリンジ[＃1、＃2、＃3、＃4]と10ミリリットルの1シリンジ）を準備します。 </li><li> 「低」と表示された灌流シリンジから6ミリリットルで5 mlシリンジ＃1を記入し（ステップ1.5を参照してください）​​。これは、約2μgの投与量に相当します。 </li><li> 「中」と表示された灌流シリンジから6ミリリットルと5ミリリットルのシリンジ＃2を入力します。これは、約20μgの投与量に相当します。 </li><li> 「ハイ」と表示された灌流シリンジから5.5ミリリットルと5ミリリットルの注射器＃3を入力します。これは、約100μgの投与量に相当します。 </li><li>ラベルされた灌流シリンジから11ミリリットルと10ミリリットル注射器を埋めます4;高い」これは、約200μgの投与量に相当します。 </li><li> 「ハイ」と表示された灌流シリンジから4.5ミリリットルと5ミリリットルの注射器＃4を入力します。これは、約80μgの投与量に相当します。この注射器は脇に置くだけ右冠動脈の評価のためにそれを使用しています。 </li></ol> 3.診断冠動脈造影<ol><li>近くに右橈骨動脈（メピバカインの通常2ミリリットル）または右大腿動脈（メピバカインの通常15ミリリットル）に近接していずれかの局所麻酔を注入します。 </li><li>局所麻酔の成功を確認して針で麻酔-肌を刺す痛みがまだ存在する場合には、患者に尋ねることです。 </li><li>カニューレを通してワイヤーを挿入し、それを削除した後、カニューレとセルジンガー法13に従って動脈を穿刺。ワイヤ上のシース（通常は5F）を挿入します。無菌条件下で冠動脈造影を行います。 </li><li>ワイヤー番目を進めますラフシース上行大動脈へと大動脈弁の上に診断カテーテルを配置します。その後、ワイヤを削除し、コントラストシリンジでカテーテルを接続します。 注：造影剤はイオメプロール、トロメタモール、塩酸と水を含んでいます。 </li><li>少し引っ張り、カテーテルを回転させることにより、左主茎で左冠動脈の診断カテーテルを配置します。造影剤の2ミリリットルを注入することによって、カテーテルの正確な位置を確認してください。 </li><li>異なるビューで冠状動脈を視覚化するため、コントラストの約10ミリリットルの手動注射でジャドキンス技術14に従って冠動脈造影を行います。 注：通常、LAO 40°とRAO 35°は右冠動脈に使用され、LAO 45°/ CRAN 25°、RAO 30°/ CRAN 30°RAO 20°/ CAUD 30°を左冠動脈に使用されます。 </li><li>関連する心外膜狭窄（の除外後にアセチルコリンテストを開始≥50視覚的評価による％）。 </li></ol>アセチルコリンの4冠動脈内注入<ol><li>左冠状動脈に2μgの注射器＃1の6ミリリットルを注入します。連続ECGのモニタリングおよび患者の症状（ 例えば 、胸痛、息切れ、めまい）で20秒以内にこれを注入します。 6ミリリットルの注射の後に左冠状動脈（通常はRAO 20°/ CAUD 30°の投影が最良の投影である）の冠動脈造影を行います。 </li><li>カテーテルに造影シリンジを介して手動でコントラストの10ミリリットルを注入することにより、冠動脈造影を行います。 12リード-ECGを記録し、アセチルコリンのすべての用量の後に印刷されるべきです。 1分の休止は、すべての用量の間であるべきです。 </li><li>左冠動脈に20μgの注射器＃2の6ミリリットルを注入します。連続ECGのモニタリングおよび患者の症状と20秒以内にこれを注入します。注射後の左冠動脈の冠動脈造影を行います上記6としてmlで。 </li><li>左冠状動脈に100μgの注射器＃3の5.5ミリリットルを注入します。連続ECGのモニタリングおよび患者の症状と20秒以内にこれを注入します。前述のように5.5ミリリットルを注入した後、左冠動脈の冠動脈造影を行います。 注：ほとんどの患者は、いくつかの症状を報告し、この用量でのECG変化または心外膜血管収縮を示します。時々手動注入の速度を遅くする必要があります。 ACH-テストのための異なるプロトコルの下で述べたように、注射の異なる速度で使用されています。 20秒以内に注射と比較して3分間にわたって、より遅い注入も可能であってもよいです。 </li><li>何の痙攣（ すなわち &gt; 90％の血管収縮を200μgnitroglyercine注射後の血管の弛緩状態と比較して）100μgの用量で発生していない場合は200μg（10ミリリットル注射器）ACHの用量を続行します。連続モニターを20秒以内に11ミリリットルを注入ECGおよび患者の症状のING。 </li><li> （セクション3）上記のように11ミリリットルを注入した後、左冠動脈の冠動脈造影を行います。 注：200μgの用量は、多くの患者に適用されてきたが、それは、冠動脈内アセチルコリンの適切な用量は、完全に定義されずに残っていることに言及すべきです。一部の著者は、100μgのは、左冠動脈の最大用量であるべきであることを示唆しています。 注：多くの場合、徐脈が発生し、射出速度を遅くする必要があります。 </li><li>異常所見は左冠状動脈のテスト中に見られない場合は右冠動脈に80μgののACH（4.5ミリリットル、シリンジ＃4）を注入します。連続ECGのモニタリングおよび患者の症状と20秒以内にこれを注入します。しばしば徐脈が発生し、注入の速度は、長期徐脈または不全収縮を防止するために減速する必要があります。 </li><li>右冠動脈の冠動脈造影を行います（セクション3）上記のように4.5ミリリットルを注入した後（通常はLAO 40°/ 0°の投影が最適です）。 </li><li>試験後の各試験を動脈への200μgの用量のとき、または重度の症状（ すなわち、激しい胸痛または高度の息切れ）、虚血性心電図シフトまたは心外膜けいれんが起こると冠動脈内ニトログリセリンを注入します。 </li><li>画像痙攣の復帰を文書化するために、1分後にステップ4.2で述べたように容器。 </li></ol>

<ol>
	<li>Prinzmetal, M., Kennamer, R., Merliss, R., Wada, T., Bor, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angina+pectoris.+I.+A+variant+form+of+angina+pectoris;+preliminary+report.">Angina pectoris. I. A variant form of angina pectoris; preliminary report.</a> Am J Med. 27, 375-388 (1959).</li><li>Cheng, T. O., Bashour, T., Kelser, G. A., Weiss, L., Bacos, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variant+angina+of+Prinzmetal+with+normal+coronary+arteriograms.+A+variant+of+the+variant.">Variant angina of Prinzmetal with normal coronary arteriograms. 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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quality+of+life,+employment+status,+and+anginal+symptoms+after+coronary+angioplasty+or+bypass+surgery.+3-year+follow-up+in+the+Randomized+Intervention+Treatment+of+Angina.">Quality of life, employment status, and anginal symptoms after coronary angioplasty or bypass surgery. 3-year follow-up in the Randomized Intervention Treatment of Angina.</a> Circulation. 94 (2), 135-142 (1996).</li><li>Ong, P., Athanasiadis, A., Borgulya, G., Mahrholdt, H., Kaski, J. C., Sechtem, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High+prevalence+of+a+pathological+response+to+acetylcholine+testing+in+patients+with+stable+angina+pectoris+and+unobstructed+coronary+arteries.+The+ACOVA+Study+(Abnormal+COronary+VAsomotion+in+patients+with+stable+angina+and+unobstructed+coronary+arteries).">High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries).</a> J Am Coll Cardiol. 59 (7), 655-662 (2012).</li><li>Furchgott, R. F., Zawadzki, J. 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D., Ogawa, K., Hara, A., Nakamura, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coronary+artery+vasoreactivity+to+intracoronary+acetylcholine+infusion+test+in+patients+with+chest+pain+syndrome.">Coronary artery vasoreactivity to intracoronary acetylcholine infusion test in patients with chest pain syndrome.</a> Intern Med. 31 (1), 22-27 (1992).</li><li>Montalescot, 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=2013+ESC+guidelines+on+the+management+of+stable+coronary+artery+disease:+the+Task+Force+on+the+management+of+stable+coronary+artery+disease+of+the+European+Society+of+Cardiology.">2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology.</a> Eur Heart J. 34 (38), 2949-3003 (2013).</li><li>JCS Joint Working Group. <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+diagnosis+and+treatment+of+patients+with+vasospastic+angina+(Coronary+Spastic+Angina)+(JCS+2013).">Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013).</a> Circ J. 78 (11), 2779-2801 (2014).</li><li>Ong, P., Athanasiadis, A., Sechtem, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patterns+of+coronary+vasomotor+responses+to+intracoronary+acetylcholine+provocation.">Patterns of coronary vasomotor responses to intracoronary acetylcholine provocation.</a> Heart. 99 (17), 1288-1295 (2013).</li><li>Seldinger, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Catheter+replacement+of+the+needle+in+percutaneous+arteriography;+a+new+technique.">Catheter replacement of the needle in percutaneous arteriography; a new technique.</a> Acta radiol. 39 (5), 368-376 (1953).</li><li>Judkins, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+coronary+arteriography.+I.+A+percutaneous+transfemoral+technic.">Selective coronary arteriography. I. 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The authors have nothing to disclose.

カテーテル法の研究室で日常の臨床ルーチンにおけるアセチルコリンの試験を実施することが可能です。別にACH溶液の調製からの放射線透過性ECGなどのテストを開始すると、連続12リードECG登録に至る前に解決しなければならないいくつかの技術的な問題があります。これは、試験中に一過性虚血性心電図変化を検出することができることが不可欠です。また、ACH溶液は2時間だけを使用する?...

狭心症は、冠動脈疾患の顕著な特徴と長年にわたって確立されている心筋虚血および運動誘発性狭心症を引き起こす心外膜狭窄の概念です。しかし、狭心症患者の多くは、ニトログリセリンや休息によって運動や救済時に胸骨の痛み、発症の典型的なトライアドを持っていません。頻繁に患者は狭心症、安静時狭心症または労作と休息狭心症の組み合わせだけでなく、可能性狭心症と同等として労作時の息切れを報告しています。 1959年プリンツメタルは、心電図（ECG）上のST上昇に関連した安静時狭心症を引き起こす冠状動脈の一過性痙攣の概念を最初に導入したが、保存運動能力1としました。この仮説は後に冠動脈造影を用いて確認し、冠攣縮が心外膜狭窄または正常な冠状動脈2の患者に存在することができると思われました。 1980iで冠動脈攣縮の検出のためのES冠動脈内アセチルコリン誘発試験（ACH-テストは）日本に設立され、冠攣縮のための臨床研究に続いて興味が3に増加しました。 しかし、1977年に経皮的冠動脈インターベンションの導入と1986年に第1のステント移植後の冠動脈血管運動障害への関心は、少なくともヨーロッパやアメリカではかなり減少しました。これは、ACH-テスト（によるACHの短い半減期にそれが唯一の冠攣縮の評価のために冠状動脈に投与することができる）の侵襲的性質のためであってもよいです。それでも、心筋虚血の徴候や症状の多くの患者は、冠動脈造影の4,5,6に関連するすべての心外膜狭窄を持っていません。このような患者では冠動脈内アセチルコリン誘発試験は、臨床的に関連する冠動脈血管運動障害を検出し、適切な薬物療法を提起することが有用です<sup&gt; 7。 アセチルコリンは副交感神経系における神経伝達物質です。これは、ニコチンと同様にムスカリン（のmAChR）受容体を介して作用します。後者は血管の恒常性に重要であり、アセチルコリンは、非選択的アゴニストとしてのmAChRに結合します。血管平滑筋細胞上のmAChRの活性化は血管収縮8に導く一方、内皮レベルでのこれらの受容体の活性化は、一酸化窒素媒介性血管拡張をもたらします。内皮の完全性と平滑筋細胞の反応性に応じて冠動脈内アセチルコリン投与の正味の効果は、血管拡張または血管収縮です。ヒトにおけるアセチルコリンに応答して、冠状動脈の生理学的反応は完全には理解されていないが、正常な冠状動脈を有する患者に示すように血管拡張だけでなく、血管径の25％までの血管収縮は生理学的であり得ることが報告されており、ノー狭心症のPECtoris 9。 冠動脈内アセチルコリン誘発試験は、欧州の学会心臓病のガイドライン10ならびに狭心症と遮るもののない冠状動脈を有する患者における心外膜および/ ​​または微小血管攣縮の評価のための日本循環器学会のガイドライン11によって推奨されています。冠動脈内アセチルコリン誘発試験は、標準化されたプロトコルが12を踏襲してきた2006年から2003年における当社の機関のカテーテル検査室で日々の臨床ルーチンに設立されました。 ACH-試験は、一般的に冠動脈造影にまだ心筋虚血の徴候や症状を持つすべての患者に該当心外膜狭窄（&lt;50％）を実行されません。 ACH-試験は、以下に記載のプロトコルに従って診断冠動脈造影法の直後に行われます。エルゴノビンは異なる作用機序を持つ攣縮誘発試験のために使用されている別の薬剤です。詳しいですエルゴノビンのテストに関する情報は、他の場所で12見つけることができます。

<table border="0" cellpadding="0" cellspacing="0" width="923">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:528px;">Vial of 20 mg acetylcholine chloride powder and 1 Ampoule of 2 mL diluent</td>
			<td style="width:151px;">Bausch &#38; Lomb&#160;</td>
			<td style="width:165px;">NDC 24 208-539-20</td>
			<td style="width:80px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3 x 100 ml NaCl 0.9 %</td>
			<td>BBraun</td>
			<td>3200950</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">3 x syringe 50 ml each</td>
			<td>BBraun</td>
			<td>4187903</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">&#160;1 x 2 ml syringe</td>
			<td>BBraun</td>
			<td>4606027V</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">&#160;1 x 10 ml syringe</td>
			<td>BBraun</td>
			<td>4606108V</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">2 x cannula 20 G 70mm</td>
			<td>BBraun</td>
			<td>4665791</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">&#160;5 x 5 ml syringe</td>
			<td>BBraun</td>
			<td>4606051V</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Contrast agent Imeron 350 with a 10ml syringe for contrast injection</td>
			<td>Bracco Imaging</td>
			<td>30699.03.00</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Coronary angiography suite (AXIOM Artis MP eco )</td>
			<td>Siemens</td>
			<td>n/a</td>
			<td></td>
		</tr>
	</tbody>
</table>

intracoronary acetylcholine provocation testing for assessment of coronary vasomotor disorders

Intracoronary acetylcholine provocation testing (ACH-test) is an established method for assessment of epicardial coronary artery spasm in the catheterization laboratory which was introduced more than 30 years ago. Due to the short half-life of acetylcholine it can only be applied directly into the coronary arteries. Several studies have demonstrated the safety and clinical usefulness of this test. However, acetylcholine testing is only rarely applied in the U.S. or Europe. Nevertheless, it has been shown that 62% of Caucasian patients with stable angina and unobstructed coronary arteries on coronary angiography suffer from coronary vasomotor disorders that can be diagnosed with acetylcholine testing. In recent years it has been appreciated that the ACH-test not only assesses the presence of epicardial spasm but that it can also be useful for the detection of coronary microvascular spam. In such cases no epicardial spasm is seen after injection of acetylcholine but ischemic ECG shifts are present together with a reproduction of the patient's symptoms during the test. This article describes the experience with the ACH-test and its implementation in daily clinical routine.

アセチルコリンテストの解釈は、3つの基準に基づいています。まず、患者は症状が発生するかどうかを試験中に求められます。多くの場合、患者は、そのような胸の痛み、息または他の症状の息切れとしての通常の症状の再現を報告しています。これはテストの全体的な解釈のために重要なポイントを表します。第二に、12-リードECG登録は継続的に、このようなST低?...

Watch this Scientific Journal Video about Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders at JoVE.com

Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders

Intracoronary acetylcholine testing has been established for the assessment of epicardial coronary spasm more than 30 years ago. Recently, the focus has shifted towards the microcirculation and it has been shown that microvascular spasm can be detected using ACH-testing. This article describes the ACH-test and its implementation in daily routine.

冠動脈血管運動障害の評価のための冠動脈内アセチルコリン挑発テスト

Intracoronary acetylcholine provocation testing (ACH-test) is an established method for assessment of epicardial coronary artery spasm in the ...

intracoronary-acetylcholine-provocation-testing-for-assessment

Research

JoVE Journal

Medicine

15.5K ビュー.  Robert-Bosch-Krankenhaus. Intracoronary acetylcholine testing has been established for the assessment of epicardial coronary spasm more than 30 years ago. Recently, the focus has shifted towards the microcirculation and it has been shown that microvascular spasm can be detected using ACH-testing. This article describes the ACH-test and its implementation in daily routine.

ビデオ: Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment1. Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech.
The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis ALS

Objective assessments of the physiological mechanisms that support speech are needed to monitor disease onset and progression in persons with ALS and to quantify treatment effects in clinical trials. In this video, we present a comprehensive, instrumentation-based protocol for quantifying speech motor performance in clinical populations.

筋萎縮性側索硬化症における延髄機能障害の包括的評価（ALS）のためのプロトコル

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression ...

医学

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. ...

Modified Technique for Coronary Artery Ligation in Mice

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 we need better knowledge about pathophysiology of myocardial ischemia. This knowledge may be valuable to define new therapeutic targets for innovative cardiovascular therapies4. Experimental MI model in mice is an increasingly popular small-animal model in preclinical research in which MI is induced by means of permanent or temporary ligation of left coronary artery (LCA)5. In this video, we describe the step-by-step method of how to induce experimental MI in mice.
The animal is first anesthetized with 2% isoflurane. The unconscious mouse is then intubated and connected to a ventilator for artificial ventilation. The left chest is shaved and 1.5 cm incision along mid-axillary line is made in the skin. The left pectoralis major muscle is bluntly dissociated until the ribs are exposed. The muscle layers are pulled aside and fixed with an eyelid-retractor. After these preparations, left thoracotomy is performed between the third and fourth ribs in order to visualize the anterior surface of the heart and left lung. The proximal segment of LCA artery is then ligated with a 7-0 ethilon suture which typically induces an infarct size ~40% of left ventricle. At the end, the chest is closed and the animals receive postoperative analgesia (Temgesic, 0.3 mg/50 ml, ip). The animals are kept in a warm cage until spontaneous recovery.

The surgical procedure used to induce experimental myocardial infarction in mice begins with left thoracotomy between the third and the fourth ribs in order to visualize the anterior surface of the heart and left lung. The left coronary artery is ligated, the chest is closed and the mouse is allowed to recover spontaneously.

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 ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination is disrupted by spinal cord injury (SCI), control of respiratory muscles innervated below the injury level is compromised1,2 leading to respiratory muscle dysfunction and pulmonary complications. These conditions are among the leading causes of death in patients with SCI3. Standard pulmonary function tests that assess respiratory motor function include spirometrical and maximum airway pressure outcomes: Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Maximal Inspiratory Pressure (PImax) and Maximal Expiratory Pressure (PEmax)4,5. These values provide indirect measurements of respiratory muscle performance6. In clinical practice and research, a surface electromyography (sEMG) recorded from respiratory muscles can be used to assess respiratory motor function and help to diagnose neuromuscular pathology. However, variability in the sEMG amplitude inhibits efforts to develop objective and direct measures of respiratory motor function6. Based on a multi-muscle sEMG approach to characterize motor control of limb muscles7, known as the voluntary response index (VRI)8, we developed an analytical tool to characterize respiratory motor control directly from sEMG data recorded from multiple respiratory muscles during the voluntary respiratory tasks. We have termed this the Respiratory Motor Control Assessment (RMCA)9. This vector analysis method quantifies the amount and distribution of activity across muscles and presents it in the form of an index that relates the degree to which sEMG output within a test-subject resembles that from a group of healthy (non-injured) controls. The resulting index value has been shown to have high face validity, sensitivity and specificity9-11. We showed previously9 that the RMCA outcomes significantly correlate with levels of SCI and pulmonary function measures. We are presenting here the method to quantitatively compare post-spinal cord injury respiratory multi-muscle activation patterns to those of healthy individuals.

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury

The purpose of this publication is to present our original work on a multi-muscle surface electromyographic approach to quantitatively characterize respiratory muscle activation patterns in individuals with chronic spinal cord injury using vector-based analysis.

慢性脊髄損傷患者で呼吸器モータ制御評価（RMCA）を使用して呼吸筋活動の評価

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

A Novel Application of Musculoskeletal Ultrasound Imaging

Ultrasound is an attractive modality for imaging muscle and tendon motion during dynamic tasks and can provide a complementary methodological approach for biomechanical studies in a clinical or laboratory setting. Towards this goal, methods for quantification of muscle kinematics from ultrasound imagery are being developed based on image processing. The temporal resolution of these methods is typically not sufficient for highly dynamic tasks, such as drop-landing. We propose a new approach that utilizes a Doppler method for quantifying muscle kinematics. We have developed a novel vector tissue Doppler imaging (vTDI) technique that can be used to measure musculoskeletal contraction velocity, strain and strain rate with sub-millisecond temporal resolution during dynamic activities using ultrasound. The goal of this preliminary study was to investigate the repeatability and potential applicability of the vTDI technique in measuring musculoskeletal velocities during a drop-landing task, in healthy subjects. The vTDI measurements can be performed concurrently with other biomechanical techniques, such as 3D motion capture for joint kinematics and kinetics, electromyography for timing of muscle activation and force plates for ground reaction force. Integration of these complementary techniques could lead to a better understanding of dynamic muscle function and dysfunction underlying the pathogenesis and pathophysiology of musculoskeletal disorders.

We describe a new ultrasound-based vector tissue Doppler imaging technique to measure muscle contraction velocity, strain and strain rate with sub-millisecond temporal resolution during dynamic activities. This approach provides complementary measurements of dynamic muscle function and could lead to a better understanding of mechanisms underlying musculoskeletal disorders.

筋骨格超音波画像の新規応用

Ultrasound is an attractive modality for imaging muscle and tendon  motion during dynamic tasks and can provide a complementary methodological  approach ...

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 ...

'Boden Food Plate': Novel Interactive Web-based Method for the Assessment of Dietary Intake

Different methods can be used in research to assess dietary intake, many of which are still paper-based. Written estimated food diaries are often utilized in clinical trials, despite being a burden for both study participants and researchers. This method requires participant literacy, it is time consuming, labor intensive, and can easily lead to under-reporting. With advancements in technology, there is a growing interest in electronic diaries that automate the dietary assessment process. These are focused on improving accuracy, reducing both time and cost and providing users with a visual and more enjoyable experience. The methodology presented here aimed to validate the &#39;Boden Food Plate&#39;, a novel web-based platform for self-recording of food and drink items, compared to a traditional estimated food diary. The application was also rated on a satisfaction scale by study participants using a paper-based questionnaire. Sixty-seven participants completed the dietary measures on both the three-day electronic and paper food diaries. For the analysis, only dietary data completed at both study time points (baseline and week six) was utilized. Despite small mean differences between dietary data collection methods, Bland Altman analysis showed fairly wide 95% limits of agreement between the electronic platform and the written estimated food diary and there were few cases which did not fall within the 95% confidence intervals. Overall, participants found the electronic food diary to be more fun than the paper method and as easy to use as hard copy diaries. The new platform has potential as a self-recording tool for the collection of dietary data, particularly when utilized in clinical trial settings. However, further validation studies are needed to improve the validity of this novel electronic dietary data collection tool.

The &#39;Boden Food Plate&#39; is an electronic food diary designed to be an interactive and fun method to collect dietary intake using visual depictions. The purpose of this study was to validate the web-based application against a traditional three-day estimated food diary method.

「ボーデン食品皿」: インタラクティブな Web ベース手法の食事摂取量の評価

Different methods can be used in research to assess dietary intake, many of which are still paper-based. Written estimated food diaries are often utilized ...

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ischemic injury. The extent of coronary damage and the mechanisms of vascular repair are factors influencing the future development of MACEs. Intrinsic vascular features like the plaque characteristics and coronary artery complexity have demonstrated prognostic information for MACEs. However, the use of intracoronary circulating biomarkers has been postulated as a convenient method for the early identification and prognosis of MACEs, as they more closely reflect dynamic mechanisms involving coronary damage and repair. Determination of coronary circulating biomarkers during angioplasty, such as the number of subpopulations of mononuclear progenitor cells (MPCs) as well as the concentration of soluble molecules reflecting inflammation, cell adhesion, and repair, allows for assessment of future developments and the prognosis of MACEs 6 months post coronary angioplasty. This method is highlighted by its translational nature and better performance than peripheral blood circulating biomarkers regarding prediction of MACEs and its effect on the cardiovascular prognosis, which may be applied for risk stratification of patients with coronary artery disease undergoing angioplasty.

Development of major adverse cardiovascular events, which impact cardiovascular prognosis after coronary angioplasty, are influenced by the extent of coronary damage and vascular repair. The use of novel coronary cellular and soluble biomarkers, reactive to vascular damage and repair, are useful to predict the development of MACEs and prognosis.

冠動脈血管形成術後の心血管予後における冠動脈前駆細胞と可溶性バイオマーカー

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ...

In Vitro Model of Coronary Angiogenesis

Here, we describe an in vitro culture assay to study coronary angiogenesis. Coronary vessels feed the heart muscle and are of clinical importance. Defects in these vessels represent severe health risks such as in atherosclerosis, which can lead to myocardial infarctions and heart failures in patients. Consequently, coronary artery disease is one of the leading causes of death worldwide. Despite its clinical importance, relatively little progress has been made on how to regenerate damaged coronary arteries. Nevertheless, recent progress has been made in understanding the cellular origin and differentiation pathways of coronary vessel development. The advent of tools and technologies that allow researchers to fluorescently label progenitor cells, follow their fate, and visualize progenies in vivo have been instrumental in understanding coronary vessel development. In vivo studies are valuable, but have limitations in terms of speed, accessibility, and flexibility in experimental design. Alternatively, accurate in vitro models of coronary angiogenesis can circumvent these limitations and allow researchers to interrogate important biological questions with speed and flexibility. The lack of appropriate in vitro model systems may have hindered the progress in understanding the cellular and molecular mechanisms of coronary vessel growth. Here, we describe an in vitro culture system to grow coronary vessels from the sinus venosus (SV) and endocardium (Endo), the two progenitor tissues from which many of the coronary vessels arise. We also confirmed that the cultures accurately recapitulate some of the known in vivo mechanisms. For instance, we show that the angiogenic sprouts in culture from SV downregulate COUP-TFII expression similar to what is observed in vivo. In addition, we show that VEGF-A, a well-known angiogenic factor in vivo, robustly stimulates angiogenesis from both the SV and Endo cultures. Collectively, we have devised an accurate in vitro culture model to study coronary angiogenesis.

In vitro models of coronary angiogenesis can be utilized for the discovery of the cellular and molecular mechanisms of coronary angiogenesis. In vitro explant cultures of sinus venosus and endocardium tissues show robust growth in response to VEGF-A and display a similar pattern of COUP-TFII expression as in vivo.

冠動脈血管新生のインビトロモデル

Here, we describe an in vitro culture assay to study coronary angiogenesis. Coronary vessels feed the heart muscle and are of clinical importance. Defects ...

Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders

More than 50% of patients with signs and symptoms of myocardial ischemia undergoing coronary angiography have unobstructed coronary arteries. Coronary vasomotor disorders (impaired vasodilatation and/or enhanced vasoconstriction/spasm) represent important functional causes for such a clinical presentation. Although impaired vasodilatation may be assessed with non-invasive techniques such as positron emission tomography or cardiac magnetic resonance imaging, there is currently no reliable non-invasive technique for the diagnosis of coronary spasm available. Thus, invasive diagnostic procedures (IDP) have been developed for the diagnosis of coronary vasomotor disorders including spasm testing as well as assessment of coronary vasodilatation. The identification of the underlying type of disorder (so called endotype) allows the initiation of targeted pharmacological treatments. Despite the fact that such an approach is recommended by the current European Society of Cardiology guidelines for the management of chronic coronary syndromes based on the CorMicA study, comparability of results as well as multicenter trials are currently hampered by major differences in institutional protocols for coronary functional testing. This article describes a comprehensive IDP protocol including intracoronary acetylcholine provocation testing for diagnosis of epicardial/microvascular spasm, followed by Doppler wire-based assessment of coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) in search of coronary vasodilatory impairment.

Coronary vasomotion disorders represent frequent functional causes of angina in patients with unobstructed coronaries. The underlying mechanism of angina (endotype) in these patients can be determined by a comprehensive invasive diagnostic procedure based on acetylcholine provocation testing followed by Doppler-derived assessment of the coronary flow reserve and microvascular resistance.

冠動脈血管運動障害の侵襲的診断のためのアセチルコリンとそれに続くアデノシンの検査

More than 50% of patients with signs and symptoms of myocardial ischemia undergoing coronary angiography have unobstructed coronary arteries. Coronary ...