Effects of capsaicin pretreatment on expiratory laryngeal closure during pulmonary edema in lambs

Abstract

The present study, performed in nonsedated, conscious lambs, consisted of two parts. In the first part, we 1) examined for the first time whether a respiratory response to pulmonary C-fiber stimulation could be elicited in nonsedated newborns and 2) determined whether this response could be abolished by capsaicin pretreatment. Then, by using capsaicin-desensitized lambs, we studied whether pulmonary C fibers were involved in the sustained, active expiratory upper airway closure previously observed during pulmonary edema. Airflow and thyroarytenoid and inferior pharyngeal constrictor muscle electromyographic activities were recorded. In the first set of experiments, a 5-10 microg/kg capsaicin bolus intravenous injection in seven intact lambs consistently led to a typical pulmonary chemoreflex, showing that C fibers are functionally mature in newborn lambs. In the second series of experiments, eight lambs pretreated with 25-50 mg/kg subcutaneous capsaicin did not exhibit any respiratory response to 10-50 microg/kg intravenous capsaicin injection, implicating C fibers in the response. Finally, in the above capsaicin-desensitized lambs, we observed that halothane-induced high-permeability pulmonary edema did not cause the typical response of sustained expiratory upper airway closure seen in the intact lamb. We conclude that functionally mature C fibers are present and responsible for a pulmonary chemoreflex in response to capsaicin intravenous injection in nonsedated lambs. Capsaicin pretreatment abolishes this reflex. Furthermore, the sustained expiratory upper airway closure observed during halothane-induced pulmonary edema in intact nonsedated lambs appears to be related to a reflex involving stimulation of pulmonary C fibers.

Laryngeal narrowing during nasal ventilation does not originate from bronchopulmonary C-fibers

“…Neonatal injection of high doses of capsaicin is well known to induce both a selective degeneration and functional ablation of CFEs (Jancso et al, 1977), which we previously confirmed in newborn lambs (Diaz et al, 1999). Accordingly, CFEs were blocked on the first recording afternoon by a subcutaneous injection of 25 mg/kg of capsaicin (diluted in 10% Tween 80, 10% ethanol and 80% physiological saline) under a 30-min general anesthesia.…”

“…i.e., at least 1 tidal volume above functional residual capacity. In addition, CFE stimulation can lead to active laryngeal closure, including in lambs (Diaz et al, 1999), which is of high relevance for our studies. From these premises, the overall aim of our ongoing investigations is to uncover the bronchopulmonary receptor type(s) involved in the active, inspiratory laryngeal narrowing observed during nPSV.…”

“…Accordingly, CFEs were blocked on the first recording afternoon by a subcutaneous injection of 25 mg/kg of capsaicin (diluted in 10% Tween 80, 10% ethanol and 80% physiological saline) under a 30-min general anesthesia. The integrity of bronchopulmonary CFEs was assessed by inducing pulmonary chemoreflexes by intravenous (IV) injections of 5 and 10 µg/kg capsaicin under intact CFE conditions, while effective CFE blockade was verified by IV injection of 50 µg/kg capsaicin (Diaz et al, 1999).…”

“…The short burst of EaTA, disappearing well before the end of the inspiratory pressure plateau in nPSV (see figure 3 in Moreau-Bussière et al, 2007), does not suggest the involvement of SAR. While both RARs and CFEs are also stimulated by lung distension (Coleridge JCG and Coleridge HM, 1984;Coleridge HM and Coleridge JCG, 2011), our previous observation that stimulation of pulmonary CFEs in lambs triggers post-inspiratory EaTA (Diaz et al, 1999), together with the availability of our robust lamb model with blocked CFEs, prompted us to assess the potential involvement of CFEs in inspiratory laryngeal narrowing during nPSV. The present demonstration that CEFs are not involved leads us now to suggest that this inspiratory laryngeal narrowing most likely originates from RAR stimulation.…”

“…From these premises, the overall aim of our ongoing investigations is to uncover the bronchopulmonary receptor type(s) involved in the active, inspiratory laryngeal narrowing observed during nPSV. The specific aim of the present study was twofold: i) to take advantage of our unique newborn lamb model with blocked CFEs (Diaz et al, 1999) in order to assess whether CFEs are involved; ii) to perform exploratory experiments to test whether the few published tools used to modulate RAR or SAR function are operative in lambs.…”