ONTOGENY OF AIRWAY SMOOTH MUSCLE FUNCTION

气道平滑肌功能的个体发育

• 批准号: 3473252
• 负责人: KENNETH T NAKAMURA
• 金额: $ 7.47万
• 依托单位: KAPI'OLANI MEDICAL CENTER/WOMEN/CHILDRN
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473252
• 关键词: acetylcholine; beta adrenergic agent; bronchus; calcium channel blockers; controlled environment; cyclic AMP; cyclic GMP; gestational age; growth /development; guinea pigs; histamine; histology; hyperoxia; mature animal; muscle contraction; muscle function; muscle relaxants; newborn animals; perfusion; premature infant animal; respiratory distress syndrome of newborn; respiratory epithelium; smooth muscle; statistics /biometry; trachea

Neonatal respiratory distress syndrome (RDS) may be complicated by a forma of unresolved lung injury referred to as bronchopulmonary dysplasia (BPD). Treatment of RDS is believed to be partially responsible for the emergence of BPD by mechanisms such as oxygen toxicity. Many studies suggest that BPD is characterized in part by reactive airway disease in addition to lung parenchymal damage. On the other hand, while bronchodilators are frequently employed in the routine management of these infants, other studies suggest that large-airway collapse may complicate BPD and that bronchodilators may at times worsen airway obstruction by promoting large airway relaxation. Thus, abnormal airway smooth muscle tone probably plays an important role in the symptoms of BPD. Herein are described studies on isolated airway smooth muscle from 6 groups of guinea pigs: 1) term newborns between 1-3 days of age, randomized to breathe room air for 2-3 days; 2) or to breathe 95% oxygen for 2-3 days; 3) 6 week old adults (controls); 4) 6 week old adults that have been exposed to 95% oxygen in the newborn period for 2-3 days; 5) preterm newborns delivered 3-6 days prior to term and allowed to breathe room air; and 6)preterm newborns exposed to 95% oxygen as described for groups #2. These experiments will first define the normal ontogeny of airway smooth muscle responses to physiologic and pharmacologic stimuli in order to test the overall hypothesis that exposure to high oxygen concentrations during the newborn period alters the normal developmental pregression of airway smooth muscle function. The technique of isometric force measurements on segments of tracheal and bronchial rings will be employed to determine the following specific aims: 1) Determine if the normal ontogeny of airway smooth muscle response sis altered after exposure to high oxygen concentrations during the newborn period to physiologic, pharmacologic and environmental stimuli; 2) Determine if the effect of airway epithelial function during normal development changes after high oxygen exposure during the newborn period; 3) Determine if gestational age at birth influences airway smooth muscle reactivity following exposure to high oxygen concentrations; and 4) Determine if relaxation responses mediated by cAMP and cGMP correlate with measurements of intracellular cAMP and cGMP accumulation. The importance of these studies is best expressed by a recent NHLBI workshop summary on "Postnatal lung development in health and disease" that recommended that the "sequence of events leading to the early development of chronic lung diseases in neonates, . . . needs to be defined. The relative importance of oxygen toxicity, . . . and airway reactivity as etiologic factors in this disease process must be examined." (30). Thus, results of studies proposed herein hold the promise of achieving new knowledge that the NHLBI feel should be "given the highest priority" (30).

新生儿呼吸窘迫综合征（RDS）可能并发一种形式， 未解决的肺损伤称为支气管肺发育不良（BPD）。 RDS的治疗被认为是部分原因， BPD的机制，如氧中毒。 许多研究表明， BPD的特征部分在于除了肺外的反应性气道疾病。 实质损伤 另一方面，虽然支气管扩张剂是 经常用于这些婴儿的日常管理，其他 研究表明，大气道塌陷可能使BPD复杂化， 支气管扩张剂有时可通过促进大的 呼吸道松弛 因此，异常的气道平滑肌张力可能起作用， 在BPD的症状中起着重要作用。 本文描述了以下研究： 来自6组豚鼠的分离的气道平滑肌：1）长期 1-3日龄的新生儿，随机呼吸室内空气2-3 天; 2）或呼吸95%氧气2-3天; 3）6周龄成人 （对照）; 4）6周龄的成年人，暴露于95%的氧气中， 新生儿期为2-3天; 5）早产儿分娩3-6天 在足月前，允许呼吸室内空气;以及6）早产新生儿 如第2组所述暴露于95%氧气。 这些实验将 首先定义气道平滑肌对 生理和药理刺激，以测试整体 假设新生儿期间暴露于高氧浓度 周期改变气道平滑肌的正常发育进程 功能 在节段上的等长力测量技术 将使用气管和支气管环来确定以下内容 具体目的：1）确定气道平滑肌的正常个体发育是否 在暴露于高氧浓度后， 新生儿期对生理、药理和环境刺激的反应; 2)确定是否影响气道上皮功能在正常 新生儿期高氧暴露后的发育变化; 3)确定出生时胎龄是否影响气道平滑肌 暴露于高氧浓度后的反应性;以及4） 确定cAMP和cGMP介导的舒张反应是否与 测量细胞内cAMP和cGMP积累。 的重要性 这些研究的最佳表达是最近的NHLBI研讨会摘要， “产后肺发育的健康和疾病”，建议， “导致慢性肺疾病早期发展的一系列事件” 新生儿疾病。. .需要定义。 的相对重要性 氧中毒。. .和气道反应性作为致病因素， 这个疾病过程必须加以检查。“（30）。 因此，研究结果 本文提出的承诺，实现新的知识，NHLBI 应该“给予最高优先权”（30）。