(762.8) The superior laryngeal nerve is involved in a brief apneic response to intralaryngeal, but not in the lethal ventilatory arrest to intravenous, administration of fentanyl (FNT) in rats

Poster Board Number: E535

Jianguo Zhuang (Lovelace Biomedical Research Institute), Shan Shi (Lovelace Biomedical Research Institute), Xiuping Gao (Lovelace Biomedical Research Institute), Fadi Xu (Lovelace Biomedical Research Institute)

Rapid intravenous (IV) injection of FNT induces a sudden ventilatory arrest within a few minutes or even seconds, which is the major cause of overdose FNT-induced death. Our previous studies have shown that right atrial or IV bolus injection of FNT in anesthetized rats produced a vagal-mediated apnea or a lethal ventilatory arrest in a dose-dependent manner (Zhuang et al, AJP 2012 and EB Meeting 2022). The superior laryngeal nerve (SLN) containing the laryngeal sensory afferents also travels in the vagus nerve and is capable of triggering the apneic response associated with hypertension and bradycardia upon activation. Here, we asked whether local administration of FNT into the larynx affected cardiorespiratory activities via acting on the SLN and to what extent the sudden ventilatory arrest induced by IV injection of FNT depended on the SLN integrity. FNT at 15 µg was either sprayed (5-10 µl) into the larynx or bolus IV-injected (50 µl) in the anesthetized rats with and without bilateral SLN transection. We found that FNT sprayed into the larynx induced an immediate brief apnea (~3.5-fold of baseline TE) and laryngeal constriction (but not closure) associated with hypertension and bradycardia. The cardiorespiratory response disappeared after transection of SLN. Interestingly, the same dose of FNT given by IV injection induced a ventilatory arrest (apneic duration gt;8-fold longer than that produced by the local administration) associated with laryngeal closure, hypotension and bradycardia. These responses to IV injection of FNT were not significantly affected by SLN transection. Our data suggest that the SLN is responsible for the brief apneic response to laryngeal application of FNT, but not for the lethal ventilatory arrest induced by rapid IV injection of FNT.