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

注:冠状动脉内乙酰胆碱的测试已通过当地伦理委员会和协议符合我们对人类的研究机构的指导方针。 1.乙酰胆碱溶液的制备（见材料表） <ol><li>混合20毫克乙酰胆碱与2 mL萃取溶剂设有包。 </li><li> 2 mL萃取液ACH加入98毫升氯化钠0.9％。这对应于剂量的0.2毫克/毫升和被称为原液1.9毫升原液1添加到91的氯化钠毫升0.9％，这对应于一个剂量18微克/毫升的并称为原液2。 </li><li>制备标为"高"，"中"和"低"3灌注注射器（各50毫升）中。填写标记为"高"用40ml原液2灌注注射器1。 </li><li>用8ml灌注注射器1（高）的填充灌注注射器2（标记为"中"），并添加32氯化钠0.9毫升％。这对应于剂量为3.6微克/毫升。 </li><li>填写灌注注射器3（标有"低"），用4毫升注射器灌注2（介质），并添加36毫升的氯化钠0.9％。这对应于一个剂量的0.36微克/毫升。 </li></ol> 2.准备的注射器中乙酰胆碱的冠脉内注射<ol><li>准备用于冠脉内注射5注射器（4-注射器5毫升[＃1，＃2，＃3，＃4]和10毫升1注射器）。 </li><li>填写5毫升注射器1＃从标有"低"灌注注射器6毫升（见步骤1.5）。这对应于一个剂量的约2微克。 </li><li>填写5毫升注射器＃2与标有"中等"灌注注射器6毫升。这对应于一个剂量的大约20微克。 </li><li>填写5毫升注射器＃3从标有"高"灌注注射器5.5毫升。这对应于一个剂量大约100微克。 </li><li>从标有灌注注射器填充10毫升注射器与11毫升4;高"这相当于一个剂量大约200微克。 </li><li>填写5毫升注射器＃4从标有"高"灌注注射器4.5毫升。这对应于剂量约80微克。把这个注射器放在一边，只使用它的右冠状动脉的评估。 </li></ol> 3.冠状动脉造影诊断<ol><li>注入局部麻醉或接近右桡动脉（通常2毫升mepivacain的），或者在接近所述右股动脉（通常15毫升mepivacain的）。 </li><li>确认局部麻醉的成功是刺麻醉，皮肤针，问病人是否疼痛仍然存在。 </li><li>根据Seldinger技术13用套管穿刺动脉，然后通过套管插入导线并将其取出。插入在导线的护套（通常5F）。在无菌条件下进行冠状动脉造影。 </li><li>推进钢丝日粗鞘到升主动脉，并放置在主动脉瓣上方的诊断导管。然后取出电线与造影剂针筒连接导管。 注:造影剂包含碘美普尔，氨丁三醇，盐酸和水。 </li><li>通过轻轻地拉动和转动导管放置在左主干左冠状动脉诊断导管。通过注入2毫升造影剂的确认导管的正确定位。 </li><li>根据朱德金斯技术14大约10毫升的对比手动进样想象中不同的意见冠状动脉进行冠状动脉造影。 注意:一般LAO 40°和饶35°被用于右冠状动脉和LAO 45°/ CRAN 25°，RAO 30°/ CRAN 30°和RAO 20°/ CAUD 30°用于左冠状动脉。 </li><li>任何相关的心外膜狭窄排除后开始测试乙酰胆碱（≥50％）通过视觉评估。 </li></ol> 4.乙酰胆碱的内注射<ol><li>注入6毫升2微克注射器＃1到左冠状动脉。 20秒，连续监测ECG和患者的症状（ 例如胸痛，呼吸急促，头晕）的内注入此。 6毫升注射后，进行左冠状动脉（通常为20 RAO°/ CAUD 30°投射最佳投影）的冠状动脉造影。 </li><li>通过经由造影注射器插入导管手动注入的10ml对比度进行冠状动脉造影。 12导心电图应记录和乙酰胆碱的每一个剂量后打印。 1分钟的暂停应该每剂量之间。 </li><li>注入6毫升20微克注射器＃2的入左冠状动脉。 20秒，连续监测心电图和病人的症状内注入此。执行注射后左冠状动脉冠状动脉造影如上所述6毫升。 </li><li>注入5.5毫升100微克注射器＃3的进入左冠状动脉。 20秒，连续监测心电图和病人的症状内注入此。 5.5 ml为上述注射后执行左冠状动脉冠状动脉造影。 注意:大多数患者报告某些症状，表明在这个剂量的心电图改变或心外膜血管收缩。有时需要手动喷射的速度减慢。如下为ACH-测试不同的协议中提到在与不同的速度喷射的用途。较慢的注射经过一段相比20秒内注射3分钟也可能是可行的。 </li><li>如果没有痉挛（ 即 &gt; 90％血管收缩相比，容器200微克nitroglyercine注射后的松弛状态）发生在100微克剂量继续与200微克（10毫升注射器）的ACH剂量。注射20秒，连续监测仪内的11毫升ING心电图和病人的症状。 </li><li>上述（第3节）提到11毫升注射后执行左冠状动脉冠状动脉造影。 注意:虽然200微克剂量已在许多患者被应用于它应该提到的是适当剂量冠状动脉内乙酰胆碱的仍有待充分定义。一些作者建议100微克应该是左冠状动脉的最大剂量。 注意:通常心动过缓发生，需要减慢喷射​​的速度。 </li><li>注入80微克的ACH（4.5毫升，注射器＃4）到右冠状动脉，如果没有异常发现是左冠状动脉的测试期间看到。 20秒，连续监测心电图和病人的症状内注入此。常心动过缓发生并且需要被减慢，以防止长时间心动过缓和/或心搏停止喷射的速度。 </li><li>执行右冠状动脉冠状动脉造影4.5毫升（通常是LAO 40°/ 0°投影最好）上述（第3节）如所述的注射后。 </li><li>冠脉内注射硝酸甘油剂量为200微克到每个测试动脉试验后，或者当严重的症状（ 如严重的胸痛或严重的呼吸困难），心电图缺血性移位或心外膜痉挛发生。 </li><li>图片如步骤4.2中提到在一分钟后记录痉挛逆转血管。 </li></ol>

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The authors have nothing to disclose.

是可行的实现在日常临床常规的乙酰胆碱试验在导管实验室。除了ACH溶液的制备有一些必须解决之前开始测试，包括透亮心电图导联连续12导联心电图注册的几个技术问题。这是为了能够在测试过程中，以检测短暂性脑缺血的心电图改变是至关重要的。此外，重要的是要知道，ACH溶液只能用于2小时。之后，他们应该被重新制备。 它询问关于测试（已知或未知）期间发生的任?...

心绞痛是冠状动脉疾病的标志和心外膜狭窄引起心肌缺血和运动诱导型心绞痛已多年建立的概念。然而，许多心绞痛患者没有被硝酸甘油或休息运动和救灾过程中的胸骨后疼痛，发作典型的黑社会。频繁的患者报告在休息或劳力和休息心绞痛的组合在劳累型心绞痛，以及呼吸急促作为可能的心绞痛当量。 1959年是变异型率先推出冠状动脉致使与心电图（ECG）ST段抬高相关休息心绞痛短暂痉挛的概念，但保留运动能力1。这一假设后来证实使用冠状动脉造影和它似乎冠状动脉痉挛可存在于患者的心外膜狭窄或正常冠状动脉2。在1980iES冠状动脉内乙酰胆碱激发试验（ACH测试）检测冠状动脉痉挛成立于日本，随后有兴趣的临床研究冠状动脉痉挛增加了3。 然而，在1977年引进的经皮冠状动脉介入，并于1986年第一次支架植入术后冠状动脉血管舒缩失调的利息至少在欧洲和美国的大幅度下降。这可能是也由于ACH-测试的侵入性（由于ACH的短半衰期它只能施用到冠状动脉冠状动脉痉挛的评估）。尽管如此，许多患者的症状和心肌缺血症状没有对冠状动脉造影4,5,6任何相关的心外膜狭窄。在这些患者冠状动脉内乙酰胆碱激发试验是非常有用的检测临床相关的冠状动脉血管舒缩障碍，并建立适当的药物治疗<sup&gt; 7。 乙酰胆碱是在副交感神经系统的神经递质。它通过烟碱和毒蕈碱（mAchR的）受体的作用。后者是用于血管稳态的重要和乙酰胆碱上mAchR的结合作为非选择性激动剂。这些受体在内皮水平的活化导致一氧化氮介导的血管扩张，而在血管平滑肌细胞mAchR的活化导致血管收缩8。取决于内皮的完整性和平滑肌细胞的反应性冠状动脉内乙酰胆碱给药的净效应是血管舒张或血管收缩。冠状动脉响应于人类乙酰胆碱的生理反应尚不完全清楚，但据报道，由于示于正常的患者冠状动脉和血管舒张以及血管直径的高达25％的血管收缩可能是生理无心绞痛PEC托里斯9。 冠状动脉内乙酰胆碱激发试验已被建议的指导方针心脏病10欧洲社会以及为患者心绞痛和通畅的冠状动脉心外膜和/或微血管痉挛的评估日本流通协会指南11。冠状动脉内乙酰胆碱激发试验已经建立在日常临床常规我们在2003年机构的导管实验室自2006年以来的标准化协议一直跟着12。 ACH-测试通常是在所有患者的症状和心肌缺血症状的冠状动脉造影执行还没有相关的外膜狭窄（&lt;50％）。 ACH-测试是根据下面描述的协议之后冠状动脉造影诊断立即执行。麦角]是用于痉挛激发试验与不同作用机制的另一个代理。详细在测试麦角新的信息可以在其他地方12被发现。

<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.

乙酰胆碱试验的解释是基于三个标准。首先，患者在整个测试发生与否症状问。通常情况下，患者汇报自己平时的症状，如胸痛，呼吸急促或困难等症状再现。这代表了测试的总体解释一个重要的一点。二，12导联心电图登记持续整个试验过程中，特别强调对缺血的心电图变化如ST段压低，ST段抬高和T波交替进行。三，冠状动脉造影是乙酰胆碱的剂量每次经过反复比较，硝...

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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.

冠状动脉内乙酰胆碱激发试验冠状动脉的血管收缩评估疾病

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 次观看.  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.

视频: 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.

延髓功能障碍肌萎缩性脊髓侧索硬化症（ALS）的综合评估议定书

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

科研

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.

悬重系统的使用在小鼠冠状动脉闭塞

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.

检测乙酰胆碱，然后使用腺苷进行冠状动脉血管舒缩疾病的侵入性诊断

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.

介入诊断程序:冠状动脉血管功能评估实用指南

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.

冠状动脉内给药硝酸甘油后乙酰胆碱再挑战

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.

测量心肌乳酸生成用于诊断冠状动脉微血管痉挛

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.

标准化大鼠冠状动脉环制备及实时记录血管直径动态张力变化

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.

氧合敏感性心脏 MRI 联合血管主动呼吸操作用于冠状动脉微血管功能障碍的无创评估

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.