Inhaled nitric oxide

吸入一氧化氮

• 批准号: 6909827
• 负责人: WARREN Myron ZAPOL
• 金额: $ 37.13万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6909827
• 关键词: SDS polyacrylamide gel electrophoresis; disease /disorder model; endotoxins; free radical oxygen; genetically modified animals; laboratory mouse; leukotrienes; lipoxygenase; lung injury; nitric oxide; nonhuman therapy evaluation; polymerase chain reaction; pulmonary hypertension; pulmonary respiration; respiratory circulation; respiratory disorder chemotherapy; respiratory epithelium; respiratory hypoxia; respiratory pharmacology; respiratory therapy; sheep; vascular endothelium; vasomotion

DESCRIPTION (provided by applicant): This grant proposes preclinical studies to improve the utility and efficacy of inhaled nitric oxide (NO). This laboratory has reported pioneering studies providing evidence that inhaled NO gas produces selective Pulmonary vasodilation. Inhaling low levels of NO has been shown to selectively reverse pulmonary vasoconstriction due to hypoxia and other stimuli and increase systemic oxygenation by selectively vasodilating ventilated lung regions in patients and animal models of acute lung injury. Since1999, over 120,000 patients per year have breathed low levels of NO to treat pulmonary hypertension and acute respiratory failure. Unfortunately, approximately 40% of patients do not respond to NO inhalation with pulmonary vasodilation and improved oxygenation. The etiology of this variable response remains incompletely understood. Studies supported by this grant will have four aims: (1) identify mediators of the impaired hypoxic pulmonary vasoconstriction (HPV) due to endotoxin-induced lung injury, (2) elucidate the roles of NO, leukotrienes, and reactive oxygen species in the impairment of HPV associated with ventilator-induced lung injury (VILI), (3) examine the role of leukotrienes in the impairment of pulmonary vascular responsiveness to inhaled NO in acute lung injury, and (4) evaluate the impact of inhibitors of leukotriene signaling, as well as nitric oxide inhalation, on the development of VILI. Studies proposed in the first three acute lung injury due to endotoxemia and high tidal volume ventilation. New therapeutic approaches developed as a result of studies in mice will be tested in a second species, the lamb, as a key next step before bringing these new strategies to the patient bedside. By understanding the nature of the interaction of endogenous and inhaled NO and leukotriene synthesis in the pulmonary vascular dysfunction associated with acute lung injury, the proposed studies should enhance the utility of inhaled NO therapy in acute lung injury.

描述（由申请人提供）： 该基金提出了临床前研究，以提高吸入一氧化氮（NO）的效用和疗效。本实验室报告了一些开创性的研究，提供了吸入NO气体产生选择性肺血管舒张的证据。在急性肺损伤的患者和动物模型中，吸入低水平的NO已显示出选择性逆转由于缺氧和其他刺激引起的肺血管收缩，并通过选择性血管舒张通气肺区域来增加全身氧合。自1999年以来，每年有超过120，000名患者吸入低水平的NO来治疗肺动脉高压和急性呼吸衰竭。不幸的是，大约40%的患者对吸入NO没有反应，肺血管舒张和氧合改善。这种可变反应的病因仍不完全清楚。该补助金支持的研究将有四个目标：（1）鉴定由于内毒素诱导的肺损伤导致的受损的缺氧性肺血管收缩（HPV）的介质，（2）阐明NO、白三烯和活性氧在与呼吸机诱导的肺损伤（VILI）相关的HPV损伤中的作用，（3）检查白三烯在急性肺损伤中肺血管对吸入NO的反应性受损中的作用，和（4）评估白三烯信号传导抑制剂的影响，以及吸入一氧化氮对VILI的影响。研究建议在前三个急性肺损伤由于内毒素血症和大潮气量通气。在小鼠研究中开发的新治疗方法将在第二个物种-羔羊中进行测试，作为将这些新策略带到患者床边的关键下一步。通过了解与急性肺损伤相关的肺血管功能障碍中内源性和吸入性NO与白三烯合成的相互作用的性质，拟议的研究应提高吸入性NO治疗急性肺损伤的实用性。