The parasympathetic nervous system is believed to play a dominant role in the mediation of the exaggerated bronchomotor responses of so-called hyperreactive airways. The precise nature of this parasympathetic involvement is unknown. The search for the parasympathetic mechanism involved in these pathophysiological bronchomotor responses is severely hampered by our incomplete knowledge of how normal bronchomotor tone and responses are regulated. The ultimate goal of this study is to extend our knowledge of the mechanisms controlling normal bronchomotor tone so that we might improve our changes of discovering the role played by parasympathetic mechanisms in causing hyperreactive airways. The key to understanding the neural control of normal airway smooth muscle tone could be linked to the understanding of the magnitude and pattern of the motor discharge reaching the parasympathetic ganglion neurons which are located in the walls of the airways. While we know that bronchomotor tone reaches minimal levels in the absence of this preganglionic activity, not much else is known, with any degree of certainty, about how changes in its pattern and magnitude alter the pattern and magnitude of changes in bronchomotor tone; about its relationship to ventilatory effort; about how it might be altered at the peripheral ganglionic level by local reflexes or about the central nervous system location of the cells whose axons transmit the preganglionic activity to the airways. The major objective of this study is to address these areas about which we know so little. Dogs will be used as the experimental model since the parasympathetic nervous system is known to dominate bronchomotor tone in this species. Some will be trained and chronically instrumented for repeated use in the normal unmedicated state throughout the duration of the study. This chronic preparation will permit simultaneous measurements of ventilation, inspiratory and expiratory electromyograms and airway smooth muscle tone from an isolated tracheal segment. Others will be studied acutely in an anesthetized, and sometimes both anesthetized and paralyzed state so that efferent activity to the airway smooth muscle can be monitored and related to the measurements of ventilatory drive being made. The combination of acute experiments and those in trained unmedicated chronically prepared dogs will provide unique information about the way in which the autonomic nervous system regulates normal airway smooth muscle tone.
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