Nitric Oxide Inhalation For Myocardial Ischemia

尽管药物治疗和血运重建术对于缓解许多冠状动脉疾病（CAD）患者的胸痛症状是有效的，但其他患者要么对药物治疗无反应，要么耐受药物治疗，要么尝试血运重建术失败。对于越来越多的患者，需要新的治疗方法。本方案的目的是测试吸入一氧化氮（NO）对在传统医疗和血运重建管理中失败的CAD患者缓解诱导心肌缺血的有效性。我们的假设是，血液中富集的一氧化氮从肺部运输到冠状动脉血管，吸入一氧化氮可以通过扩张冠状动脉和小动脉来改善应激时心肌的血流量。本研究的主要终点是与室内空气呼吸时的运动时间相比，吸入一氧化氮时在跑步机上运动时间的改善，次要终点的选择是提供一氧化氮缓解诱导性缺血的机制，包括对以下方面的影响：1)动脉输送和心肌提取一氧化氮转运分子，2)心肌灌注，3)整体和局部心肌收缩力。该临床试验是随机、双盲和安慰剂（室内空气）控制的设计，CAD患者在每次压力测试前用NO（或室内空气）呼吸约1小时，然后在测试两天后交叉到替代治疗。一氧化氮吸入的益处证明可以为CAD患者提供一个重要的治疗选择，以缓解心肌缺血。

Although medical therapy and revascularization procedures are effective for relief of chest pain symptoms in many patients with coronary artery disease (CAD), others either do not respond to or tolerate medical therapies, or have failed attempts at revascularization. For this growing number of patients, there is a need for novel therapeutic approaches. The purpose of this protocol is to test the effectiveness of nitric oxide (NO) inhalation for the relief of inducible myocardial ischemia in patients with CAD who have failed conventional attempts at medical and revascularization management. Our hypothesis is that enriched NO transport in blood from the lungs and delivery to the coronary vasculature with NO inhalation will improve blood flow to the myocardium during stress by dilating coronary arteries and arterioles. The primary end-point of this study is improvement in treadmill exercise duration during NO inhalation compared with exercise duration during room air breathing, with secondary end-points selected to provide mechanistic insight as to relief of inducible ischemia by NO, including effects on: 1) arterial delivery and myocardial extraction of NO transport molecules, 2) myocardial perfusion, and 3) global and regional myocardial contractility. This clinical trial is randomized, double-blind, and placebo (room air)-controlled in design, with CAD patients treated with NO (or room air) breathing for approximately1 hour before each stress test, followed by crossover to the alternate therapy after two days of testing. Demonstration of benefit from NO inhalation could result in an important therapeutic option for CAD patients with few alternatives for the relief of myocardial ischemia.