INHALED NITRIC OXIDE

该基金建议对以下机制进行重要的实验室研究： 吸入一氧化氮（NO）的作用和毒理学。 本实验室 吸入低水平的一氧化氮是一种选择性的 逆转缺氧性肺血管收缩的肺血管扩张剂。 应用NO与NO混合液复苏缺氧新生绵羊， 弥漫性急性肺损伤 吸入一氧化氮可以改善 成人呼吸窘迫的肺通气与灌注 综合征（ARDS）。 吸入NO也是一种快速而深刻的支气管扩张剂 在动物模型中。 这项拨款建议进行实验室研究， 内源性和外源性肺NO产生的相互作用，以及 为了了解NO合酶抑制剂是否可以增加有益的 吸入NO对脓毒性肺损伤的影响 缺氧新生儿 绵羊呼吸性和代谢性酸中毒对NO诱导的 将探索肺血管舒张。 在豚鼠中， NO将在炎症刺激增强的气道张力上进行检查 （白三烯）。 将进行仔细的病理分析 研究吸入NO的任何毒性作用， 正常成年和新生大鼠肺。 以这种方式，我们 将提高对NO吸入作为一种 支气管痉挛，肺血管收缩， 弥漫性急性肺部炎症。

This grant proposes important laboratory studies of the mechanisms of action and toxicology of inhaled nitric oxide (NO). Our laboratory has reported that inhaling low levels of nitric oxide is a selective pulmonary vasodilator that reverses hypoxic pulmonary vasoconstriction. NO has mixtures were used to resuscitate hypoxic newborn sheep and treat diffuse acute lung injury. Inhaling nitric oxide improves the matching of pulmonary ventilation with perfusion in the Adult Respiratory Distress Syndrome (ARDS). Inhaled NO is also a rapid and profound bronchodilator in animal models. This grant proposes laboratory studies to examine the interaction of endogenous and exogenous pulmonary NO production, and to learn whether NO synthase inhibitors can augment the beneficial effects of NO inhalation in septic lung injury. In hypoxic newborn sheep the effects of respiratory and metabolic acidosis on NO induced pulmonary vasodilation will be explored. In guinea pigs the effects of NO will be examined on airway tone augmented by inflammatory stimuli (leukotrienes). A careful pathological analysis will be undertaken searching for any toxic effects of inhaling NO for periods up to one month upon normal adult and newborn rat lungs. In this manner our understanding will be enhanced of the safety of NO inhalation as a therapeutic agent in states of bronchospasm, pulmonary vasoconstriction, and diffuse acute pulmonary inflammation.