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.