血管内皮功能的超声评估：血流介导的舒张试验的技术指导原则
Summary
The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans. Although the FMD test has been related with the prediction of future cardiovascular disease and events, it is a physiological assessment with many inherent confounding factors that need to be considered.
Abstract
心血管疾病是死亡的主要原因和残疾的主要病因全世界。血管内皮功能障碍是一种病理状况，其特征主要由中断在血管舒张和血管收缩的物质之间的平衡，并提出在动脉粥样硬化的心血管疾病的发展中发挥重要的作用。因此，血管内皮功能在人类一个准确的评估，是一个重要的工具，可以帮助人们更好地理解多心为中心的病症的病因。
在过去的25年里，许多方式方法已被开发，以提供内皮功能的评估在人中。在1989年推出的口蹄疫测试采用了前臂闭塞和随后的反应性充血，促进一氧化氮的产生和肱动脉血管舒张。现在口蹄疫测试是使用最广泛的，非侵入性，ULTR在人类和内皮功能asonic评估已经与未来心血管事件相关联。
虽然口蹄疫测试可能有临床应用，它是继承了需要考虑的几个混杂因素生理评估。本文介绍了确定口蹄疫包括推荐的方法，以帮助减少生理和技术问题，提高了评价的精度和可重复性的标准化协议。
Introduction
心血管疾病是全世界发病率和死亡率的首要原因。血管内皮功能障碍表示朝向多种血管相关疾病的发展1的初始阶段。因此，血管内皮功能的人类的准确评估是一个重要的技术，可以帮助理解多种心血管病症的病因，以改善治疗和预防疾病的疗效的最终目标。
内皮
内皮是细胞单层该合成众多血管活性物质，诸如一氧化氮（NO），前列环素，内皮素，内皮细胞生长因子，白细胞介素，和纤溶酶原抑制剂2。这些因素有助于内皮的功能来调节血液的流动性，血管张力，血小板聚集，血浆成分和血管壁INFL的渗透性ammation 2-4。此外，没有在促进血管扩张和维持内皮完整性的关键抗动脉粥样硬化的作用。通过控制输送氧气到组织和它们的代谢需求3,5-之间的平衡NO调节血管张力和直径。有多个内源性，外源性，和机械刺激因子诱导内皮NO合酶（eNOS），它从NO合成的L-精氨酸6,7。最显着的机械刺激是剪切应力。壁剪切应力与eNOS更大激活，导致NO的产生和随后的平滑肌松弛4。出于这个原因中的NO生物利用度的减少通常被用作内皮功能障碍8的量度。
内皮功能障碍
血管扩张和血管收缩因子之间的失衡导致内皮机能障碍2。此外，relea炎症介质和改变的局部剪切力本身可以提高内皮衍生的活性氧（ROS）的合成。这种上调在氧化还原不仅信令 修改内皮的完整性，并降低NO 9的合成，它可以脱开的eNOS导致直接生产的额外自由基。最终，这改善中的NO生物利用度促进血管收缩，血管硬度，降低动脉扩张4。
内皮功能障碍的程度已与若干疾病，如其中包括高血压10，动脉粥样硬化11，缺血性中风12，糖尿病13，先兆子痫14或肾脏疾病15的严重程度有关。因此，有广阔的兴趣，不仅评估随时间的血管内皮功能的变化，也下列的治疗性干预。不同的方法已被用于在冠状动脉和外周环流19内皮功能都侵入（心导管和静脉闭塞容积描记3,16）和非侵入性（流动介导的扩张，桡动脉张力计和脉冲轮廓分析4,17,18）的临床评估。
血流介导的舒张
流动介导的舒张（FMD）是血管内皮功能的非侵入性的，超声评价，并已与血管的健康问题的发展密切相关。公司自1989年成立以来20，口蹄疫已被广泛用作可靠， 体内方法评估人类19,21,22主要是NO介导的血管内皮功能。事实上，肱动脉FMD试验已经与其他微创技术23和众多调查相关的所描述的口蹄疫和心血管损伤24,25这样INDIVI之间存在很强的负相关关系偶与更多的血管病变具有更低的FMD 25。因此，这些数据强调的预后信息，这种技术可提供，因为它涉及到未来心血管疾病中的无症状受试者26-30。
在口蹄疫检测，肱动脉的直径在基线和前臂的停循环上映后连续测量。在袖口发布，诱导反应性充血促进介导的NO释放和后续血管舒张19,31在剪切应力的增加。口蹄疫被表示为压脉袋的释放在基线直径（FMD％）相比，按照动脉直径增加的百分比。
尽管在此技术的日益临床利益，口蹄疫测试是一种生理评估，因此，几个变量需要，以便在人体中进行的血管内皮功能的精确评估被考虑。这是rticle描述的标准化协议和推荐的方法来最小化的技术和生物问题，以帮助改善口蹄疫测试的准确性，再现性和解释。
Protocol
注：以下FMD过程中中西医血管和运动生理学（LIVEP）的血管实验室评估研究常规进行。所有的程序遵循赫尔辛基宣言的原则和乔治亚大学校务由机构审查委员会的批准。所有的参与者被告知的目标和获得参与该技术可能的风险的书面同意之前， 图1说明了应考虑肱动脉口蹄疫超声评估的基本要素的概要总结。 1.除准备（在抵达前） 确认参与者从实践锻炼（≥12小时），咖?…
Representative Results
从明显健康的队列组的基线特征在表1中呈现在综合血管和运动生理学（LIVEP）的实验室进行的口蹄疫测试的最常见的变量在表2中，以下的变量被认为是主要的口蹄疫参数在公布的FMD教程4和准则36分析。 基线和峰值直径下列适当的驯化阶段?…
Discussion
在1989年20引入，口蹄疫测试已被广泛用于在人中作为内皮功能的非侵入性的措施。口蹄疫不仅被证明是预测未来的血管相关疾病的风险19,52,53，降低FMD值已经显示与心血管损伤24,25,54强烈相关。虽然也有其他的技术来评估血管内皮功能，既侵入（冠状动脉造影）和非侵入性（静脉体积描记术和手指体积描记法），口蹄疫一直是最广泛使用的，由于它的非侵入性和外周动脉功…
Declarações
The authors have nothing to disclose.
Acknowledgements
笔者想感谢谁参加了我们的研究中，我们已经评估使用FMD测试内皮功能的众多学科和病人。
Materials
| Doppler ultrasound | GE Medical Systems | Logiq 7 | Essential to include Duplex mode for simultaneous acquisition of B-mode and Doppler |
| Electrocardiographic (ECG) gating | Accusync Medical Research | Accusync 72 | |
| 12-MHz Linear array transducer | GE Medical Systems | 11L-D | A high-resolution linear array probe is essential |
| Forearm occlusion cuff | D.E. Hokanson | SC5 | 5 x 84 cm |
| Ultrasound transmission gel | Parker | 01-08 | |
| Rapid cuff inflator | D.E. Hokanson | E-20 AG101 | |
| Sterotactic-probe holder | Flexabar | 18047 | Magnetic base fine adjustor |
| Edge detection analysis software | Medical Imaging Applications | Brachial Analyzer 5 |
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Citar este artigo
Rodriguez-Miguelez, P., Seigler, N., Harris, R. A. Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test. J. Vis. Exp. (110), e54011, doi:10.3791/54011 (2016).