Upper airway cooling and l-menthol reduce ventilation in the guinea pig

Cooling of the upper airway, which stimulates specific cold receptors and inhibits laryngeal mechanoreceptors, reduces respiratory activity in unanesthetized humans and anesthetized animals. This study shows that laryngeal cooling affects the pattern of breathing in the guinea pig and assesses the potential role of cold receptors in this response by using a specific stimulant of cold receptors (l-menthol). The response to airflows (30 ml/s, 10-s duration) through the isolated upper airway was studied in 23 anesthetized (urethan, 1 g/kg ip) guinea pigs breathing through a tracheostomy. Respiratory airflow, tidal volume, laryngeal temperature, and esophageal pressure were recorded before the challenges (control), during cold airflows (25 degrees C, 55% relative humidity), and during warm airflows (37 degrees C, saturated) with or without the addition of l-menthol. Whereas warm air trials had no effect, cold air trials, which lowered laryngeal but not nasal temperature, reduced ventilation (VE) to 85% of control, mainly by prolonging expiratory time (TE, 145% of control), an effect abolished by laryngeal anesthesia. Addition of l-menthol to the warm airflow caused a greater reduction in VE (41% of control) by prolonging TE (1,028% of control). Nasal anesthesia markedly reduced the apneogenic effect of l-menthol but did not affect the response to cold air trials. In conclusion, both cooling of the larynx and l-menthol in the laryngeal lumen reduce ventilation. Exposure of the nasal cavity to l-menthol markedly enhances this ventilatory inhibition; considering the stimulatory effect of l-menthol on cold receptors, these results suggest a predominant role of nasal cold receptors in this response.