Name: intracoronary acetylcholine provocation testing for assessment of coronary vasomotor disorders
Uploaded: 2016-08-18T14:00:00.000+00:00
Duration: 6 min 39 s
Description: Watch this Scientific Journal Video about Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders at JoVE.com

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참고 : 관동맥 아세틸 콜린 테스트는 로컬 윤리위원회에 의해 승인되었으며 프로토콜이 인간 연구에 대한 우리의 기관의 지침을 따릅니다. 아세틸 콜린 솔루션 1. 준비 (재료 표 참조) <ol><li> 패키지와 함께 제공되는 용매 2 mL를 20 mg을 아세틸 콜린을 섞는다. </li><li> 염화나트륨 0.9 %의 98 ml의 2 ml의 ACH 솔루션을 추가합니다. 이것은 ml의 0.2 밀리그램 /의 복용량에 해당하고 염화나트륨의 91 ml의 0.9 %를 원액 1의 9 ML을 추가 원액 (1)라고하며, 이것은 ml의 18 μg의 /의 용량에 해당하며 원액 2라고합니다. </li><li> &quot;높음&quot; &quot;중간&quot;과 &quot;낮음&quot;으로 표시 3 관류 주사기 (50 ㎖ 각각)을 준비합니다. 원액이 40 ㎖로 &quot;높은&quot;라고 표시된 관류 주사기 1을 입력합니다. </li><li> 관류 주사기 (고 1)의 8 ml의 관류 주사기 2 (표지 &quot;매체&quot;)를 입력하고 염화나트륨 0.9 32 ml의 %를 추가합니다. 이것은에 대응3.6 μg의 / ㎖의 용량. </li><li> 관류 주사기 3 채우기 관류 주사기 2 (중) 4 ㎖로 ( &quot;낮음&quot;으로 표시)와 염화나트륨 0.9 %의 36 ml에 추가 할 수 있습니다. 이것은 0.36 μg의 / ㎖의 투여 량에 해당한다. </li></ol> 아세틸 콜린의 관동맥 주입 용 주사기 2. 준비 <ol><li> 관동맥 주입 주사기 5 준비 (5 ㎖ 4 주사기 [# 1, # 2, # 3, # 4], 10 ㎖ 주사기 1). </li><li> &quot;저&quot;로 표시된 관류 주사기 6 ㎖로 5 ML의 주사기 # 1을 작성 (단계 1.5 참조). 이 약 2 μg의의 용량에 해당한다. </li><li> &quot;매체&quot;로 표시된 관류 주사기 6 ㎖로 5 ML의 주사기 # 2를 입력합니다. 이것은 약 20 μg의 복용량에 상응한다. </li><li> &quot;높은&quot;라고 표시된 관류 주사기에서 5.5 ml의 5 ML의 주사기 # 3을 입력합니다. 이 약 100 μg의의 용량에 해당한다. </li><li> 표시된 관류 주사기에서 11 mL를 10 ML의 주사기를 채우4;. &quot;고이 약 200 μg의의 용량에 해당한다. </li><li> &quot;높은&quot;라고 표시된 관류 주사기 4.5 ml의 5 ML의 주사기 # 4를 입력합니다. 이 약 80 μg의의 용량에 해당한다. 옆이 주사기를 넣고 만 오른쪽 관상 동맥의 평가를 위해 그것을 사용할 수 있습니다. </li></ol> 3. 진단 관상 동맥 혈관 조영술 <ol><li> 국소 마취를 주입하거나 우측 요골 동맥에 근접 (통상 2 ㎖의 mepivacain) 또는 오른쪽 대퇴 동맥 (mepi​​vacain 보통 15 ㎖)에 근접한다. </li><li> 국소 마취의 성공을 확인하는 것은 바늘로 마취 피부를 따끔 따끔하고 통증이 여전히 존재하는 경우 환자를 요구하는 것입니다. </li><li> 다음 정맥을 통해 와이어를 삽입 및 제거, 캐 뉼러와 Seldinger 기술 (13)에 따라 동맥에 구멍. 와이어를 통해 시스 (일반적으로 5 층)를 삽입합니다. 무균 조건에서 관상 동맥 조영술을 수행합니다. </li><li> 와이어 일을 사전거친 상행 대동맥에 외피와는 대동맥 판막 위의 진단 카테터를 배치합니다. 이어서 상기 와이어를 제거하고, 콘트라스트 주사기 카테터를 연결한다. 주 : 조영제가 Iomeprol, 트로 메타 몰, 염산과 물이 포함되어 있습니다. </li><li> 약간 당기고 카테터를 돌려 왼쪽 원줄기의 좌측 관상 동맥의 진단 카테터를 놓습니다. 조영제 2 ㎖를 주입하여 카테터의 정확한 위치를 확인한다. </li><li> 다른보기에서 관상 동맥을 시각화 대비 약 10 ml의 수동 주사와 Judkins 기술 (14)에 따라 관상 동맥 조영술을 수행합니다. 참고 : 일반적으로 LAO 40 ° 및 RAO 35 °가 오른쪽 관상 동맥에 사용되며, LAO 45 ° / CRAN 25 °, RAO 30 ° / CRAN 30 ° 및 RAO 20 ° / CAUD 30 °가 왼쪽 관상 동맥에 사용됩니다. </li><li> (모든 관련 심 외막 협착의 배제 후 ≥50을 아세틸 콜린 테스트 시작시각적 평가에 의해 %). </li></ol> 아세틸 콜린의 4 관동맥 주입 <ol><li> 좌측 관상 동맥에 2 μg의 주사기 # 1 6 ml를 주입한다. 심전도 및 환자의 증상 (예 : 가슴 통증, 호흡 곤란, 현기증)의 지속적인 모니터링과 함께 20 초 이내에 주입. 6 ml를 주입 한 후 왼쪽 관상 동맥 (일반적으로 RAO 20 ° / CAUD 30 ° 투사 가장 프로젝션입니다)의 관상 동맥 조영술을 수행합니다. </li><li> 수동으로 카테터에 대비 주사기를 통해 대비 10 ㎖를 주입하여 관상 동맥 조영술을 수행합니다. 12 리드 ECG 기록과 아세틸 콜린의 모든 투여 후 인쇄해야합니다. 1 분의 일시 정지는 모든 용량 사이에 거짓말을한다. </li><li> 좌측 관상 동맥에 20 μg의 주사기 # 2 6 mL의 주입한다. 지속적인 심전도 모니터링 및 환자의 증상을 20 초 이내에 주입. 주사 후 왼쪽 관상 동맥의 관상 동맥 조영술을 수행6 ㎖가 전술 한 바와 같이. </li><li> 좌측 관상 동맥에 100 μg의 주사기 # 3 5.5 ml를 주입한다. 지속적인 심전도 모니터링 및 환자의 증상을 20 초 이내에 주입. 전술 한 바와 같이 5.5 ml를 주입 한 후 좌측 관상 동맥의 동맥 조영술을 수행한다. 참고 : 대부분의 환자는 어떤 증상을보고이 용량에서 ECG 변경 또는 심 외막 혈관 수축을 보여줍니다. 때로 서, 주입 속도는 느리게 할 필요가있다. ACH-테스트에 대한 서로 다른 프로토콜 아래에 언급 한 바와 같이 주입 다른 속도로 사용하고 있습니다. 20 초 이내에 주입에 비해 3 분의 기간에 걸쳐 느린 주입도 실현 될 수있다. </li><li> 더 경련 (200 μg의 nitroglyercine 주입 후 혈관의 이완 된 상태에 비해 즉,&gt; 90 % 혈관 수축)이 100 μg의 용량에서 발생하지 않으면 200 μg의 (10 ML의 주사기) ACH 투여를 계속합니다. 연속 모니터 20 초 이내에 11 ml에 주입심전도 및 환자의 증상을 보내고. </li><li> (항목 3) 상기 언급 한 바와 같이 11 ml를 주입 한 후 좌측 관상 동맥의 동맥 조영술을 수행한다. 참고 : 200 μg의 용량이 많은 환자에 적용되었지만이 관상 동맥 내 아세틸 콜린의 적절한 투여가 완전히 정의 할 수 남아 있음을 언급해야한다. 일부 저자는 100 μg의 왼쪽 관상 동맥의 최대 투여해야하는 것이 좋습니다. 참고 : 자주 서맥이 발생하고 주입 속도가 둔화 될 필요가있다. </li><li> 더 이상 소견은 좌측 관상 동맥의 테스트 기간 동안 볼 수없는 경우 오른쪽 관상 동맥에 80 μg의의 ACH (4.5 ml를, 주사기 # 4)를 주입한다. 지속적인 심전도 모니터링 및 환자의 증상을 20 초 이내에 주입. 보통 서맥이 발생하고, 사출 속도를 장시간 서맥 및 / 또는 무 수축을 방지하기 위해 감속 될 필요가있다. </li><li> 오른쪽 관상 동맥의 관상 동맥 조영술을 수행4.5 ㎖ (일반적으로 LAO 40 ° / 0 ° 투사가 최고입니다) (섹션 3) 위에서 언급 한 바와 같이 주입 후. </li><li> 상기 시험 후 각 시험 동맥에 200 μg의의 투여하거나 심각한 증상 (예 : 심한 가슴 통증이나 호흡의 심각한 곤란), 허혈성 ECG 변화 또는 심 외막 경련이 발생하여 관동맥 내 니트로 글리세린을 주입한다. </li><li> 이미지 경련의 복귀를 문서화하는 1 분 후에 단계 4.2에서 언급 한 바와 같이 용기. </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.

이는 카테터 실험실에서 매일 임상 경로에있는 아세틸 콜린 테스트를 구현 가능하다. 별도로 ACH의 용액의 제조에서 방사선 투과 ECG를 포함하여 테스트를 시작하는 연속 12 리드 ECG의 등록을 유도하기 전에 해결해야 할 몇 가지 기술적 인 문제가있다. 이 시험 동안 일과성 허혈 ECG 변화를 감지 할 수있는 것이 중요하다. 또한,이 솔루션은 ACH 단지 2 시간 동안 사용될 수 있다는 것을 아는 것이 중요?...

협심증은 관상 동맥 질환의 특징 수년 동안 확립 된 심근 허혈 및 운동성 협심증 일으키는 심 외막 협착 개념이다. 그러나, 협심증을 가진 많은 환자는 니트로 글리세린 또는 휴식으로 운동과 구호 동안 흉골 통증, 발병의 전형적인 화음이 없습니다. 자주 환자는 가능한 협심증 상응하는 등의 노력에 따라 협심증 휴식이나 운동시 및 휴식 협심증의 조합에서 협심증뿐만 아니라 호흡 곤란을보고한다. 1959 년 프린즈 메탈는 심전도 (ECG)에 ST 분절 상승과 관련된 나머지 부분에서 협심증을 유발하는 관상 동맥의 일시적인 경련의 개념을 소개하는 첫 번째하지만 보존 운동 능력 1이었다. 이 가설은 심혈관 조영술을 이용하여 나중에 확인하고 관상 동맥 경련 외막 협착 또는 정상 관상 동맥이있는 환자에 존재할 수 있다고 나타났다. 1980i에서에스 관상 동맥 경련의 검출 (ACH-테스트) 테스트 관동맥 아세틸 콜린 유발 일본에 설립 관상 동맥 경련이 3 증가에 대한 임상 연구에이어서 관심이되었다. 그러나, 1977 년 경피적 관상 동맥 중재술의 도입과 1986 년 첫 스텐트 시술 후 관상 동맥 혈관 운동 장애에 대한 관심은 적어도 유럽과 미국에서 크게 감소했다. 이것은 (그것 때문에 만 관상 동맥 경련의 평가 관상 동맥에 투여 될 수있다 ACH의 짧은 반감기)으로 인해 ACH-시험의 침략적 성격도 할 수있다. 그럼에도 불구하고, 표지판 및 심근 허혈의 증상이있는 많은 환자는 관상 동맥 조영술의 4,5,6의 모든 관련 심 외막 협착이 없습니다. 이러한 환자에서 관동맥 아세틸 콜린 유발 시험은 임상 적 관상 동맥 혈관 운동 장애를 감지하고 적절한 의료 치료를 제기하는 데 유용합니다 <sup&gt; 7. 아세틸 콜린은 부교감 신경계의 신경 전달 물질이다. 그것은 nicotinergic뿐만 아니라 muscarinergic (mAChR) 수용체를 통해 작용한다. 후자는 혈관 항상성에 중요한 아세틸 콜린은 비 선택적 작용제로서 mAChR에 결합한다. 내피 수준에서 이들 수용체의 활성화는 혈관 수축 (8)에 이어지는 혈관 평활근 세포에 mAChR의 활성화 반면 산화 질소 매개 혈관 확장을 이끈다. 내피의 무결성 및 평활근 세포의 반응성에 따라 관동맥 아세틸 콜린 투여의 순 효과는 혈관 확장 또는 혈관 수축이다. 인간의 아세틸 콜린에 응답하여 관상 동맥의 생리적 반응은 완전히 이해되지 않고, 정상 관상 동맥 환자에 도시 된 바와 같이 혈관 직경의 25 %까지의 혈관 확장과 수축이 더 생리적 될 수 있다고보고되었다 협심증 PECTORIS 9. 관동맥 아세틸 콜린 유발 검사는 심장 가이드 라인 (10)의 유럽 사회뿐만 아니라 협심증과 탁 트인 관상 동맥 환자에서 심 외막 및 / 또는 미세 혈관 경련의 평가를위한 일본의 순환 학회 가이드 라인 (11)에 의해 권장되고있다. 관동맥 아세틸 콜린 유발 시험은 표준화 된 프로토콜 (12)을 따라 한 2006 년부터 2003 년 우리 기관의 카테터 실험실에서 매일 임상 루틴에서 설립되었습니다. ACH-테스트는 일반적으로 관상 동맥 조영술 아직 징후와 심근 허혈의 증상이있는 모든 환자에서 더 중요한 심 외막 협착 (&lt;50 %) 수행되지 않습니다. ACH-시험은 이하의 프로토콜에 따라 진단 관상 동맥 조영술 직후에 수행된다. 에르고 행동의 다른 메커니즘 연축 유발 검사에 사용되는 다른 에이전트입니다. 상세한에르고 테스트에 대한 정보는 다른 곳에서 12 찾을 수 있습니다.

<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.

아세틸 콜린 시험의 해석은 세 가지 기준에 기초한다. 첫째, 환자 여부 증상이 시험 통하여 요청된다. 자주, 환자는 흉통, 호흡 또는 다른 증상의 곤란으로 자신의 평소 증상의 재생을보고합니다. 이 시험의 전반적인 해석 중요한 포인트를 나타낸다. 둘째, 12 리드 ECG 등록은 지속적으로 같은 ST 세그먼트 우울증, ST 분절 상승 및 T 파 alternans 등의 허혈성 ECG 변화에 특별한 중...

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.

평가 관상 동맥의 혈관 운동 장애에 대한 관상 동맥 내 아세틸 콜린 도발 테스트

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

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

15.6K 조회수.  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.

비디오: 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.

루게릭병에 안구 장애의 종합 평가 (ALS)에 대한 프로토콜

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

연구

의학

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.

마우스의 관상 동맥 폐색에 대한 한깅 무게 시스템의 사용

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.

관상 동맥 운동 장애의 침습적 진단을 위해 아세틸 콜린 검사 후 아데노신 검사

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.

중재 적 진단 절차 : 관상 동맥 혈관 기능 평가를위한 실용 가이드

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.

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.

관상동맥 미세혈관 경련 진단을 위한 심근 젖산 생산 측정

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.

표준화 된 쥐 관상 동맥 링 준비 및 용기 직경에 따른 동적 장력 변화의 실시간 기록

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.

관상 동맥 미세혈관 기능 장애의 비침습적 평가를 위한 혈관 활성 호흡 기동을 사용한 산소 민감성 심장 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.