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，我将完成博士学位的研究。 生理学论文研究了 暴露于猫病毒的猫中的气管平滑肌 鼻气管炎病毒。 一部分气管肌会 在体内分离并附着在力传感器上。 血和 维持气管段的神经供应，以允许本地 自主激动剂和拮抗剂的动脉内输注 神经供应分离出来用于电刺激。 两组 将研究猫。 主要群体将受到挑战 气溶胶吸入猫病毒鼻气管炎病毒，而A 对照组接收气溶胶的盐水。 两天后 挑战我将研究气管的自主法规 肌肉。 毒蕈碱活性将通过测量 剂量反应乙酰胆碱内局部输注和 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 通过检查对局部输注的剂量反应来调查 异丙肾上腺素和对颈椎刺激的反应 交感神经。 alpha1和alpha2肾上腺素能活性 由对苯肾上腺素的剂量反应确定和 可乐定。 刺激迷走神经后 副交感神经和同情封锁将证明 非肾上腺素能抑制神经系统的活性。 适当的阻滞剂将用于确定 回答。 我将确定病毒效应是否是由于上皮引起的 通过重复研究a）猫中的损伤或炎症 从孤立的气管中除去气管上皮 段，b）在贫血的猫中。 在第二阶段我会 从病毒感染恢复期间进行类似的研究 以及自主法规变化的研究机制 在第一阶段观察到的II期的特定方案将是 一旦可以使用I阶段协议的结果。 我 将仅重复已确定异常的方案 在自主法规中定义时间以确定 病毒感染后这些异常的持续时间。 对机制的调查将涉及使用特定 花生四烯酸和代谢产物的阻滞剂。 气道反应性 在猫科动物中，还将研究“哮喘”。