VIRAL-AUTONOMIC INTERACTIONS IN THE TRACHEA

气管中的病毒-自主相互作用

• 批准号: 3087434
• 负责人: CHERYL R KILLINGSWORTH
• 金额: $ 7.3万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087434
• 关键词: aerosols; alpha adrenergic receptor; alpha antiadrenergic agent; autonomic nervous system; beta adrenergic receptor; beta antiadrenergic agent; cats; chemical stimulation; electrostimulus; inflammation; inhalation drug administration; intraarterial administration; muscle function; respiratory airway pressure; respiratory epithelium; respiratory muscles; rhinovirus; smooth muscle; trachea; vagus nerve; virus diseases; virus virus interaction

In Phase I of this award I will complete the research for my Ph.D. thesis in physiology investigating the autonomic regulation of tracheal smooth muscle in cats exposed to feline viral rhinotracheitis virus. A segment of trachealis muscle will be isolated in vivo and attached to a force transducer. The blood and nerve supply to the tracheal segment is maintained to allow local intra-arterial infusion of autonomic agonists and antagonists and the nerve supply is isolated for electrical stimulation. Two groups of cats will be studied. A principal group will be challenged by aerosol inhalation of feline viral rhinotracheitis virus, while a control group receives an aerosol of saline. Two days following challenge I will study autonomic regulation of the trachealis muscle. Muscarinic activity will be investigated by measuring the dose response to local intraarterial infusion of acetylcholine and the response to electrical stimulation of the vagus nerve with increasing stimulus frequency. Beta adrenergic activity will be investigated by examining the dose response to local infusion of isoproterenol and the response to stimulation of the cervical sympathetic nerves. Alpha1 and alpha2 adrenergic activity will be determined by the dose response to phenylephrine and clonidine, respectively. Stimulation of the vagus nerve after parasympathetic and sympathetic blockade will demonstrate the activity of the non-adrenergic inhibitory nervous system. Appropriate blockers will be used to determine specificity of responses. I will determine if viral effects are due to epithelial injury or inflammation by repeating the studies a) in cats in which tracheal epithelium is removed from the isolated tracheal segment, and b) in neutrophil-depleted cats. In Phase II I will conduct similar studies during recovery from the viral infection and study mechanisms of any changes in autonomic regulation observed in Phase I. Specific protocols for Phase II will be designed once the results of protocols of Phase I are available. I will repeat only the protocols which have identified abnormalities in autonomic regulation to define the time to determine the duration of these abnormalities following viral infection. Investigations of mechanisms will involve the use of specific blockers of arachidonic acid and metabolites. Airway reactivity in feline "asthma" will also be studied.

在该奖项的第一阶段，我将完成我的博士学位研究。 生理学论文研究自主神经调节 接触猫病毒的猫的气管平滑肌 鼻气管炎病毒。 一段气管肌将 体内分离并连接到力传感器。 血液和 维持气管段的神经供应，以允许局部 动脉内输注自主神经激动剂和拮抗剂 神经供应被隔离以进行电刺激。 两组 将研究猫的数量。 主要群体将面临以下挑战： 气溶胶吸入猫病毒性鼻气管炎病毒，同时 对照组接受盐水气雾剂。 两天后 挑战 我将研究气管的自主调节 肌肉。 毒蕈碱活性将通过测量 局部动脉内注射乙酰胆碱的剂量反应 对迷走神经电刺激的反应 增加刺激频率。 β肾上腺素能活性将是 通过检查局部输注的剂量反应进行研究 异丙肾上腺素和对宫颈刺激的反应 交感神经。 α1 和 α2 肾上腺素能活性将 由对去氧肾上腺素的剂量反应确定 可乐定，分别。 刺激迷走神经后 副交感神经和交感神经阻滞将证明 非肾上腺素能抑制性神经系统的活性。 将使用适当的阻断剂来确定 回应。 我将确定病毒的影响是否是由于上皮细胞引起的 通过在猫身上重复 a) 的研究来造成损伤或炎症，其中 从分离的气管中去除气管上皮 段，和b)在中性粒细胞耗尽的猫中。 在第二阶段我将 在病毒感染恢复期间进行类似的研究 并研究自主调节任何变化的机制 在第一阶段观察到。第二阶段的具体方案将 一旦第一阶段的协议结果可用，就进行设计。 我 将仅重复已识别出异常的方案 在自主调节中定义时间来确定 病毒感染后这些异常的持续时间。 机制的调查将涉及使用特定的 花生四烯酸及其代谢物的阻滞剂。 气道反应性 还将研究猫科动物的“哮喘”。