The investigations being proposed will be carried out in direct continuation of our previous work on laryngeal and upper airway receptors, and related reflex responses. On the basis of previous observations on the effect of water solutions on laryngeal receptors activity, we will examine the possibility of modifying the strength of laryngeal reflex responses by changes in the physico-chemical composition of the mucosal surface liquid (Aim #1). A relatively common disorder, gastroesophageal reflex, has increasingly been recognized as an etiologic factor int he development of many laryngeal lesions. We will examine the effects of a HCI-pepsin solution applied to the laryngeal mucosa on the neural function of this organ: receptor transduction and related reflex responses. Histological control of the laryngeal mucosa and submucosa will be carried out to characterize the damage (inflammation, necrosis...) due to the exposure to HCI-pepsin solutions (Aim #2). The larynx is expected to be the most reactive, tussigenic-site of the entire respiratory tract and some evidence favors this expectation. However, evidence to the contrary is also available. Using a preparation in which upper and lower airway are functionally isolated, we will compare the elicitability of cough and the intensity of its efforts to comparable mechanical and chemical irritation of the larynx and the tracheobronchial tree. Moreover, we will evaluate the pattern of discharge of intrinsic laryngeal muscles and their temporal relationship to changes in subglottic pressure in laryngeal and tracheobronchial cough. We will also study any possible alteration of laryngeal muscle pattern of discharge, in tracheobronchial-elicted cough, following deafferentation of the larynx. Developmental aspects of laryngeal and tracheobronchial reactivity to noxious stimuli will be studied.
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