DIAPHRAGM NEUROMUSCULAR TRANSMISSION--HYPOXIA & MATURITY

膈肌神经肌肉传导——缺氧

• 批准号: 2226577
• 负责人: Alia R Bazzy-Asaad
• 金额: $ 16.56万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226577
• 关键词: DIAPHRAGM; NEUROMUSCULAR; TRANSMISSION; HYPOXIA; MATURITY

Over the past several years, we have been interested and have focussed on the study of respiratory muscle function, especially as it relates to the young. From our recent work, it has become evident that neuromuscular (NM) transmission failure may be one important site of diaphragmatic fatigue. This is particularly true in the immature who may be predisposed for developing respiratory failure due to transmission impairment. This has been recently demonstrated by our preliminary observations in an isolated diaphragm preparation in our laboratory. On the basis of these data and those of other investigators, we have formulated several hypotheses in this proposal: A) Neuromuscular transmission failure can play a significant role in the development of diaphragmatic fatigue in the newborn. This will be tested in the rat phrenic nerve-hemidiaphragm preparation in-vitro at several ages and examined by comparing the force generated by the muscle in response to direct and indirect (phrenic) stimulation and correlating the force level to the size, number and shape of action potentials. B) The mechanisms responsible for NM transmission failure in the newborn diaphragm are related to an imbalance between Acetylcholine (ACH) release and breakdown in the synaptic cleft. This will be tested by measuring the size of ACH quanta, the activity of specific and nonspecific esterases and by the use of blockade experiments. C) NM transmission failure in the immature is secondary to presynaptic rather than postsynaptic mechanisms and these are specific to the neuromuscular junction of specific muscle fiber types. This will be examined by analyzing the amplitude and number of end plate potentials and the safety factor of NM transmission at various frequency of stimulation and correlating these with muscle fiber type. D) NM transmission in the young is more resistant to the effects of acute stresses such as hypoxia or acidosis. In this proposal, we utilize state-of-the-art techniques and methodologies and these are either operative or currently being developed. Since proper functioning of the respiratory system is vitally dependent on the integrity of the respiratory muscles, we believe that understanding the mechanisms which lead to muscle failure will be crucial for the treatment and prevention of respiratory muscle fatigue and subsequent respiratory failure in the newly born.

在过去的几年里，我们一直感兴趣，并专注于 关于呼吸肌功能的研究，特别是当它与 年轻人。从我们最近的工作来看，很明显 神经肌肉(NM)传递失败可能是 横隔膜疲劳。这一点在那些可能 易患上由传播引起的呼吸衰竭 减损。这一点最近得到了我们初步的证明 在我们实验室的隔离隔膜制备中的观察。在……上面 根据这些数据和其他调查人员的数据，我们有 在这份提案中提出了几个假设：a)神经肌肉 变速器故障可能在以下方面发挥重要作用 新生儿的横隔膜疲劳。这将在大鼠身上进行测试 不同年龄和年龄的大鼠膈神经-横隔膜的体外制备 通过比较肌肉产生的力来检查 直接和间接(膈)刺激和相关的力量水平 动作电位的大小、数量和形状。B)机制 新生儿隔膜中NM传输失败的责任是 与乙酰胆碱(ACH)释放和分解之间的失衡有关 在突触裂隙里。这将通过测量ACH的大小来测试 量、特异酯酶和非特异酯酶的活性及其用途 封锁实验。C)未成熟IS网管传输故障 次要于突触前机制而不是突触后机制 专用于特定肌肉纤维的神经肌肉连接 类型。这将通过分析振幅和数量来检查 不同端板电势与NM传输安全系数 刺激频率并将其与肌肉纤维类型相关联。 D)在年轻人中传播新城疫对急性肺炎的影响更具抵抗力 应激，如缺氧或酸中毒。在这个提案中，我们利用 最先进的技术和方法，这些是 正在运行的或目前正在开发的。由于运行正常， 呼吸系统在很大程度上取决于 呼吸肌，我们相信了解 导致肌肉衰竭将是治疗和预防的关键 呼吸肌疲劳和随后的呼吸衰竭 刚出生的孩子。