Date of Award

4-1-1995

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physiology and Pharmacology

Abstract

This study characterizes bronchovascular and lower airway responses elicited by chemical stimuli applied to the frontal sinus or nasal mucosa of sheep, and evaluates the role of a sinu-nasal-bronchiolar neural reflex in the lower airway responses.In 18 adult sheep anesthetized with pentobarbital sodium, the frontal sinuses were trephined. After a left thoracotomy bronchial artery blood flow (Q$\rm\sb{br}$) was measured with an electromagnetic flow probe. Histamine or capsaicin was applied to the left or right frontal sinus mucosa, or the nasal mucosa, and alterations in Q$\rm\sb{br}$ and tracheal airflow measured. Airflow was measured with a pneumotachometer. Sheep were respired mechanically (5 cm H$\sb2$O PEEP).Histamine (0.1 ml, 5% w/v) applied to the sinus or nasal mucosa increased Q$\rm\sb{br}$ significantly, with a concurrent fall in bronchial vascular resistance (BVR), with a mean onset of 48 seconds and a peak response occurring 90 seconds after application. Airflow was significantly reduced by histamine application.Atropine pretreatment or transection of the ophthalmic and maxillary branches of the trigeminal nerve significantly reduced the histamine induced Q$\rm\sb{br}$ response, and prevented the histamine induced fall in airflow. Bilateral vagotomy also attenuated the response.Pretreatment with chlorpheniramine maleate following vagotomy or sensory nerve transection further attenuated the residual Q$\rm\sb{br}$ response.Capsaicin (0.1 ml, 1500 ug/ml) did not alter Q$\rm\sb{br}$, but reduced airflow to 98.5% of baseline. Transection of the ophthalmic and maxillary nerves blocked the capsaicin induced decrease in airflow.Application of chemical stimuli to the upper airway mucosa can effect alterations in tracheal airflow and lower airway blood flow and these changes are mediated primarily by a sinu-nasal-bronchovascular nerve reflex. Afferent sensory information is conducted unilaterally by the trigeminal nerve and efferent information transmitted through the vagus nerve bilaterally to the airways and bronchial circulation. This study illustrates how sensory input from the nasal or sinus mucosae can be important in acute host airway defense. This study also demonstrates a mechanism by which inflammatory mediators in the sinus may elicit effects in the lower airway and may explain why upper airway inflammation is associated with airway hyperresponsiveness and asthma.

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