Inhaled nitric oxide

吸入一氧化氮

• 批准号: 6822755
• 负责人: WARREN Myron ZAPOL
• 金额: $ 37.03万
• 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/6822755
• 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）：