Nitric Oxide Inhalation For Myocardial Ischemia

虽然内科治疗和血管重建术对缓解许多冠心病患者的胸痛症状是有效的，但其他患者要么对内科治疗无效或耐受，要么尝试血管重建术失败。对于越来越多的患者来说，需要新的治疗方法。该方案的目的是测试吸入一氧化氮(NO)对那些常规药物治疗和血管重建治疗失败的冠心病患者缓解诱导性心肌缺血的有效性。我们的假设是，在吸入NO的情况下，肺内血液中丰富的NO运输和输送到冠状动脉血管系统将通过扩张冠状动脉和小动脉来改善应激期间流向心肌的血流量。这项研究的主要终点是吸入NO期间的跑步机运动持续时间与室内空气呼吸期间的运动持续时间相比有所改善，次要终点的选择是为了从机制上了解NO诱导的缺血的缓解，包括以下方面的影响：1)动脉输送和心肌提取NO运输分子，2)心肌灌注，以及3)整体和局部心肌收缩能力。这项临床试验是随机、双盲和安慰剂(室内空气)对照的设计，在每次压力测试之前，CAD患者接受大约1小时的无(或室内空气)呼吸治疗，然后在两天的测试后交叉到替代治疗。证明吸入NO的益处可能会为冠心病患者带来一个重要的治疗选择，因为几乎没有其他选择来缓解心肌缺血。

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.