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. A variant of the variant.</a> Circulation. 47 (3), 476-485 (1973).</li><li>Yasue, H., 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=Induction+of+coronary+artery+spasm+by+acetylcholine+in+patients+with+variant+angina:+possible+role+of+the+parasympathetic+nervous+system+in+the+pathogenesis+of+coronary+artery+spasm.">Induction of coronary artery spasm by acetylcholine in patients with variant angina: possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm.</a> Circulation. 74 (5), 955-963 (1986).</li><li>Bell, M. R., Berger, P. B., Holmes, D. R., Mullany, C. J., Bailey, K. R., Gersh, B. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Referral+for+coronary+artery+revascularization+procedures+after+diagnostic+coronary+angiography:+evidence+for+gender+bias?.">Referral for coronary artery revascularization procedures after diagnostic coronary angiography: evidence for gender bias?.</a> J Am Coll Cardiol. 25 (7), 1650-1655 (1995).</li><li>Patel, M. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low+diagnostic+yield+of+elective+coronary+angiography.">Low diagnostic yield of elective coronary angiography.</a> N Engl J Med. 362 (10), 885-895 (2010).</li><li>Pocock, S. J., Henderson, R. A., Seed, P., Treasure, T., Hampton, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=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. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+obligatory+role+of+endothelial+cells+in+the+relaxation+of+arterial+smooth+muscle+by+acetylcholine.">The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.</a> Nature. 288 (5789), 373-376 (1980).</li><li>Shimizu, H., Lee, J. 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. A percutaneous transfemoral technic.</a> Radiology. 89 (5), 815-824 (1967).</li><li>Mohri, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Angina+pectoris+caused+by+coronary+microvascular+spasm.">Angina pectoris caused by coronary microvascular spasm.</a> Lancet. 351 (9110), 1165-1169 (1998).</li><li>Chandrasekar, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complications+of+cardiac+catheterization+in+the+current+era:+a+single-center+experience.">Complications of cardiac catheterization in the current era: a single-center experience.</a> Catheter Cardiovasc Interv. 52, 289-295 (2001).</li><li>Nakao, K., 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=Hyperventilation+as+a+specific+test+for+diagnosis+of+coronary+artery+spasm.">Hyperventilation as a specific test for diagnosis of coronary artery spasm.</a> Am J Cardiol. 80 (5), 545-549 (1997).</li></ol>

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><tbody><tr><td>Vial of 20 mg acetylcholine chloride powder and 1 Ampoule of 2 ml diluent</td><td>Bausch &amp;amp; Lomb&amp;nbsp;</td><td>NDC 24 208-539-20</td><td></td></tr><tr><td>3x 100 ml NaCl 0.9 %</td><td>BBraun</td><td>3200950</td><td></td></tr><tr><td>3x syringe 50 ml each</td><td>BBraun</td><td>4187903</td><td></td></tr><tr><td>1x 2 ml syringe</td><td>BBraun</td><td>4606027V</td><td></td></tr><tr><td>1x 10 ml syringe</td><td>BBraun</td><td>4606108V</td><td></td></tr><tr><td>2x cannula 20 G 70 mm</td><td>BBraun</td><td>4665791</td><td></td></tr><tr><td>5x 5 ml syringe</td><td>BBraun</td><td>4606051V</td><td></td></tr><tr><td>Contrast agent Imeron 350 with a 10 ml syringe for contrast injection</td><td>Bracco Imaging</td><td>30699.03.00</td><td></td></tr><tr><td>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

15.6K 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. ...

Quantification of Absolute Myocardial Flow and Resistance by Continuous Thermodilution in Patients with Ischemia and Nonobstructive Coronary Artery Disease (INOCA)

In approximately half of the patients undergoing coronary angiography for angina pectoris or for signs or symptoms suggestive of ischemic heart disease, no obstructive coronary artery disease is angiographically visible. The majority of these patients with angina or ischemia and no obstructive coronary artery disease (INOCA) have an underlying coronary vasomotor dysfunction, and current consensus documents recommend diagnostic invasive coronary vasomotor function testing (CFT). 
During CFT, a variety of vasomotor dysfunction endotypes can be assessed, including vasospastic coronary dysfunction (epicardial or microvascular vasospasm), and/or microvascular vasodilatory dysfunction, including impaired vasodilatory capacity and increased microvascular resistance. The quantification of the continuous thermodilution derived absolute coronary blood flow and resistance might be a better measure compared to the currently used standard physiologic measures. This article provides an overview of this continuous thermodilution method.

Quantification of Absolute Myocardial Flow and Resistance by Continuous Thermodilution in Patients with Ischemia and Nonobstructive Coronary Artery Disease INOCA

Presented here is a protocol to measure absolute myocardial flow and resistance using continuous thermodilution in patients with ischemia and nonobstructive coronary artery disease.

In approximately half of the patients undergoing coronary angiography for angina pectoris or for signs or symptoms suggestive of ischemic heart disease, ...

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 ...

Interventional Diagnostic Procedure: A Practical Guide for the Assessment of Coronary Vascular Function

Approximately 40% of patients undergoing invasive coronary angiography for investigation of angina are found to have no obstructive coronary artery disease (ANOCA). Abnormal coronary function underlies coronary vasomotion syndromes including coronary endothelial dysfunction, microvascular angina, vasospastic angina, post-PCI angina and myocardial infarction with no obstructive coronary arteries (MINOCA). Each of these endotypes are distinct subgroups, characterized by specific disease mechanisms. Diagnostic criteria and linked therapy for these conditions are now established by expert consensus and clinical guidelines.
Coronary function tests are performed as an adjunctive interventional diagnostic procedure (IDP) in appropriately selected patients during coronary angiography. This aids differentiation of patients according to endotype. The IDP includes two distinct components: a diagnostic guidewire test and a pharmacological coronary reactivity test. The tests last approximately 5 minutes for the former and 10-15 minutes for the latter. Patient safety and staff education are key.
The diagnostic guidewire test measures parameters of coronary flow limitation (fractional flow reserve [FFR], coronary flow reserve [CFR], microvascular resistance [index of microvascular resistance (IMR)], basal resistance index, and vasodilator function [CFR, resistive reserve ratio (RRR)]).
The pharmacological coronary reactivity test measures the vasodilator potential and propensity to vasospasm of both the main coronary arteries and the micro-vessels. It involves intra-coronary infusion of acetylcholine and glyceryl trinitrate (GTN). Acetylcholine is not licensed for parenteral use and is therefore prescribed on a named-patient basis. Vasodilatation is the normal, expected response to infusion of physiological concentrations of acetylcholine. Vascular spasm represents an abnormal response, which supports the diagnosis of vasospastic angina.
The purpose of this practical guide is to provide information on the preparation and administration of the IDP in clinical practice. It discusses some key preparation and safety considerations, as well as tips for procedural success. The IDP supports stratified medicine for a personalized approach to health and wellbeing.

The purpose of this practical guide is to provide information on the preparation and administration of an interventional diagnostic procedure in clinical practice. It discusses some key preparation and safety considerations, as well as tips for procedural success.

介入診断手順:冠状血管機能の評価のための実用的なガイド

Approximately 40% of patients undergoing invasive coronary angiography for investigation of angina are found to have no obstructive coronary artery ...

Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina with non-obstructive coronary artery disease (ANOCA) using acetylcholine (ACh) spasm provocation testing. CAS can further be divided into different subtypes (e.g., focal, diffuse epicardial, or microvascular spasm), each with different pathophysiological mechanisms that may require tailored drug treatment. The evidence behind the role of nitrates in the setting of each CAS subtype is lacking, and the effectivity can vary on a per-patient basis. In order to assess on a per-patient level whether nitroglycerine (NTG) can prevent inducible spasm, the vasospastic ACh dose can be readministered after NTG administration as part of the spasm provocation test. The preventive effect of NTG is assessed by evaluating improvements in the severity of induced symptoms, ischemic ECG changes, and by reassessing the site and mode of spasm on angiography. This technique can therefore be used to assess the nitrate responsiveness on a per-patient level and unmask co-existing microvascular spasm in patients with epicardial spasm that is prevented with NTG. The NTG rechallenge, therefore, allows to further guide targeted therapy for CAS and provide new insights into the pathophysiological mechanism behind vasospastic disorders.

This protocol presents the acetylcholine rechallenge after nitroglycerine as an add-on procedure to spasm provocation testing. The purpose of this technique is to unmask co-existing microvascular spasm&#160;in patients with epicardial spasm&#160;and to assess the protective efficacy of nitroglycerine on a per-patient level to guide medical therapy.

冠状動脈内ニトログリセリン投与後のアセチルコリン再チャレンジ

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina with non-obstructive coronary artery disease (ANOCA) ...

Measurement of Myocardial Lactate Production for Diagnosis of Coronary Microvascular Spasm

In about a quarter of patients with angina and non-obstructive coronary arteries, no epicardial spasm is noted on coronary arteriography during an angina attack. Since the pressure-rate product is almost identical at rest and the onset of attack in those patients, the decrease in coronary blood flow rather than increased myocardial oxygen consumption is likely to explain myocardial ischemia, indicating a substantial involvement with coronary microvascular spasm (MVS). Myocardial lactate production, which could be defined as a negative myocardial lactate extraction ratio (ratio of the coronary arterial-venous difference in lactate concentration to arterial concentration), is considered indicative of objective evidence to support the emerging myocardial ischemia. Thus, monitoring of the myocardial lactate production and the emergence of chest pain and ischemic electrocardiographic changes during acetylcholine (ACh) provocation testing is of significant value for detecting the entity of MVS. Practically, 1 min after incremental doses of ACh (20, 50, and 100 &#956;g) are administered into the left coronary artery (LCA), paired samples of 1 mL of blood are collected from the LCA ostium and coronary sinus for measurement of lactate concentration by a calibrated automatic lactate analyzer. Then, the development of MVS could be confirmed by negative myocardial lactate extraction ratio despite the absence of angiographically demonstrable epicardial coronary spasm or before its occurrence throughout ACh provocation testing. In conclusion, assessment of myocardial lactate production is essential and valuable for the diagnosis of MVS.

Myocardial lactate production (coronary arterial-venous difference in serum lactate level) during coronary spasm provocation testing is considered as a highly sensitive marker that reflects acetylcholine-induced myocardial ischemia due to microvascular spasm. This article presents the procedures to assess myocardial lactate production for the diagnosis of coronary microvascular spasm.

冠動脈微小血管痙攣診断のための心筋乳酸産生測定

In about a quarter of patients with angina and non-obstructive coronary arteries, no epicardial spasm is noted on coronary arteriography during an angina ...

Standardized Rat Coronary Ring Preparation and Real-Time Recording of Dynamic Tension Changes Along Vessel Diameter

As a key event of cardiovascular system diseases, coronary artery disease (CAD) has been widely regarded as the main culprit of atherosclerosis, myocardial infarction, and angina pectoris, which seriously threaten the life and health of people all over the world. However, how to record the dynamic biomechanical characteristics of isolated blood vessels has long puzzled people. Meanwhile, precise positioning and isolation of coronary arteries to measure in vitro dynamic vascular tension changes have become a trend in CAD drug development. The present protocol describes the macroscopic identification and microscopic separation of rat coronary arteries. The contraction and dilation function of the coronary artery ring along the vessel diameter was monitored using the established multi myograph system. The standardized and programmed protocols of coronary ring tension measurement, from sampling to data acquisition, tremendously improve the repeatability of the experimental data, which ensures the authenticity of vascular tension records after physiological, pathological, and drug intervention.

The present protocol describes the wire myograph technique for measuring vascular reactivity of the rat coronary artery.

標準化されたラット冠状動脈リング調製と血管直径に沿った動的張力変化のリアルタイム記録

As a key event of cardiovascular system diseases, coronary artery disease (CAD) has been widely regarded as the main culprit of atherosclerosis, ...

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of tissue contrast. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation. Quantifying such changes during the cardiac cycle and throughout vasoactive maneuvers can provide markers for coronary macro- and microvascular function and thereby circumvent the need for any extrinsic, intravenous contrast or pharmacologic stress agents.
OS-CMR uses the well-known sensitivity of T2*-weighted images to blood oxygenation. Oxygenation-sensitive images can be acquired on any cardiac MRI scanner using a modified standard clinical steady-state free precession (SSFP) cine sequence, making this technique vendor-agnostic and easily implemented. As a vasoactive breathing maneuver, we apply a 4-min breathing protocol of 120 s of free breathing, 60 s of paced hyperventilation, followed by an expiratory breath-hold of at least 30 s. The regional and global response of myocardial tissue oxygenation to this maneuver can be assessed by tracking the signal intensity change. The change over the initial 30 s of the post-hyperventilation breath-hold, referred to as the breathing-induced myocardial oxygenation reserve (B-MORE) has been studied in healthy people and various pathologies. A detailed protocol for performing oxygen-sensitive CMR scans with vasoactive maneuvers is provided.
As demonstrated in patients with microvascular dysfunction in yet incompletely understood conditions, such as inducible ischemia with no obstructive coronary artery stenosis (INOCA), heart failure with preserved ejection fraction (HFpEF), or microvascular dysfunction after heart transplantation, this approach provides unique, clinically important, and complementary information on coronary vascular function.

The assessment of microvascular function by oxygenation-sensitive cardiac magnetic resonance imaging in combination with vasoactive breathing maneuvers is unique in its ability to assess rapid dynamic changes in myocardial oxygenation in vivo and, thus, may serve as a critically important diagnostic technique for coronary vascular function.

冠状動脈微小血管機能障害の非侵襲的評価のための血管作動性呼吸操作を伴う酸素化感受性心臓MRI

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of ...

Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues

Altered vascular tone responsiveness to pathophysiological stimuli contributes to the development of a wide range of cardiovascular and metabolic diseases. Endothelial dysfunction represents a major culprit for the reduced vasodilatation and enhanced vasoconstriction of arteries. Adipose (fat) tissues surrounding the arteries play important roles in the regulation of endothelium-dependent relaxation and/or contraction of the vascular smooth muscle cells. The cross-talks between the endothelium and perivascular adipose tissues can be assessed ex vivo using mounted blood vessels by a wire myography system. However, optimal settings should be established for arteries derived from animals of different species, ages, genetic backgrounds and/or pathophysiological conditions.

The protocol describes the use of wire myography to evaluate the transmural isometric tension of mesenteric arteries isolated from mice, with special consideration of the modulation by factors released from endothelial cells and perivascular adipose tissues.