Effect of Intravenous Substance P on Laryngeal Adductor Activity in Young Dogs

Abstract

Reflex laryngeal adduction is a component of both the laryngeal chemoreflex and the esophagolaryngeal adductor reflex, two life-threatening reflexes that occur in immature animals. These two reflex responses are also thought to exist in infants and may play a role in causing life-threatening laryngospastic events and perhaps sudden infant death syndrome. Identifying neurotransmitters that mediate laryngeal adduction is important to understanding the mechanism of reflex laryngeal responses and to identifying potential means of pharmacologic prevention. Substance P (SP), a tachykinin, putatively functions as a sensory neurotransmitter and may play a role in mediating laryngeal reflexes. Substance P-immunoreactive-like fibers and receptors are present in the subepithelial tissues of the larynx, the vagus nerves, the nodose and jugular ganglia, and the vagal brain stem nuclei. In this investigation, the effect of SP infusion on laryngeal motor activity in an in vivo model is reported. Substance P was infused intravenously into 8 puppies (20 to 133 days of age, mean 81.2), on a mean of 3.0 occasions (range 1 to 6). Cardiovascular, respiratory, arterial blood gas, and cricothyroid (CT), thyroarytenoid (TA), and genioglossus electromyographic (EMG) responses to infusion of the tachykinin were recorded and subsequently analyzed. The SP infusion induced a marked increase in CT or TA EMG activity in 23 of 24 studies, and the increase was typically apparent within 60 seconds of the infusion. An increase in genioglossus EMG activity did not occur. An immediate, profound decrease in mean arterial pressure and an increase in respiratory rate and depth of chest wall excursion accompanied the laryngeal response. Arterial blood gas values remained unchanged (p > .05). The laryngeal adductor response to SP infusion was blocked when animals were pretreated with a systemic SP antagonist (Pfizer CP-96,345). This study demonstrates that peripheral infusion of the tachykinin SP induces a marked increase in laryngeal adductor activity. The response may be blocked by pretreatment of animals with a systemic SP antagonist. Because SP is thought to act primarily as a sensory neurotransmitter, these findings may be important in understanding the mechanism of reflex laryngeal adductor responses.

Capsaicin-induced activation of pulmonary vagal C fibers produces reflex laryngeal closure in the rat

“…N is the number of animals observed. very similar to previous reports (10,15,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) and also to the laryngeal chemoreflex (3,4). However, differences exist in the response between our present findings and these previous reports.…”

“…The cardiopulmonary chemoreflex (apnea and decreases in the blood pressure and heart rate) induced by intravenous administration of capsaicin has been well documented (7,13,(17)(18)(19)(20)(21)28). Apnea and reflex laryngeal adduction can also be induced by stimulations applied to the larynx (3,4,28) or by inhaled wood smoke (17,21).…”

“…Laryngeal adduction is a component of the pulmonary chemoreflex and laryngeal chemoreflex. The laryngeal chemoreflex can be induced by local stimulation of the laryngeal mucosa or intravenous infusion of substance P (2,3,4,30). It can also be triggered by laryngeal exposure to wood smoke (21) or a femoral injection of capsaicin (16).…”

Effect of Respiratory Syncytial Virus on Apnea in Weanling Rats

“…We repeated some of these experiments using a different viral pathogen, adenovirus, to verify whether the effect of RSV was specific or rather a nonspecific consequence of virusinduced airway inflammation. Furthermore, we explored the mechanism of apnea in our model by blocking different neurotransmitters [substance P, calcitonin gene-related peptide (CGRP), and ␥-aminobutyric acid (GABA)] that are released directly or indirectly by capsaicin and known to affect the control of ventilation (15,(17)(18)(19). Finally, we studied whether the administration of RSV-neutralizing antibodies protects against capsaicin-induced apnea and apnea-related mortality in RSV-infected rats.…”

Neurophysiology and Clinical Implications of the Laryngeal Adductor Reflex

“…Such consequences may represent a potential mechanism for the development of sudden infant death syndrome (SIDS) similar to neonates found to be at high risk for SIDS from apneas secondary to GER 36 . Work in animal models lends support to these clinical observations 37 however the cause of SIDS remains speculative.…”