Focal warming in the nucleus of the solitary tract prolongs the laryngeal chemoreflex in decerebrate piglets

Abstract

The laryngeal chemoreflex (LCR), elicited by a drop of water in the larynx, is exaggerated by mild hyperthermia (body temperature = 40-41 degrees C) in neonatal piglets. We tested the hypothesis that thermal prolongation of the LCR results from heating the nucleus of the solitary tract (NTS), where laryngeal afferents first form synapses in the brain stem. Three- to 13-day-old piglets were decerebrated and vagotomized and studied without anesthesia while paralyzed and ventilated. Phrenic nerve activity and rectal temperature were recorded. A thermode was placed in the medulla, and the brain tissue temperature was recorded with a thermistor approximately 1 mm from the tip of the thermode. When the thermode was inserted into the brain stem, respiratory activity was arrested or greatly distorted in eight animals. However, the thermode was inserted in nine animals without disrupting respiratory activity, and in these animals, warming the medullary thermode (thermistor temperature = 40-41 degrees C) while holding rectal temperature constant reversibly exaggerated the LCR. The caudal raphé was warmed focally by approximately 2 degrees C in four additional animals; this did not alter the duration of the LCR in these animals. Thermodes placed in the NTS did not disrupt respiratory activity, but they did prolong the LCR when warmed. Thermodes that were placed deep to the NTS in the region of the nucleus ambiguus disrupted respiratory activity, which precluded any analysis of the LCR. We conclude that prolongation of the laryngeal chemoreflex by whole body hyperthermia originates from the elevation of brain tissue temperature within in the NTS.

Interleukin-1β and interleukin-6 enhance thermal prolongation of the LCR in decerebrate piglets

“…Another aspect of our experimental LCR maneuvers that distinguish them from naturally occurring apneas is that the animals are continuously ventilated and so do not become hypoxic or hypercapnic during the periods of phrenic “apnea”. We found in this study and have found in previous studies somewhat variable effects of drug or changes in body temperature on respiratory frequency (Curran et al, 2005; Xia et al, 2007a, b). It is worth noting that, to the extent an increased respiratory frequency represents an increased respiratory drive, such an increase in frequency would tend to decrease, rather than increase the duration of apnea and the LCR.…”

“…These five breaths did not need to have the same frequency or amplitude as the control breaths; we simply required that they be regular (Curran et al, 2005; van der Velde et al, 2003; Xia et al, 2007b). The respiratory disruption measured in this way included both periods of unstable respiratory activity and apneas.…”

The Brainstem and Serotonin in the Sudden Infant Death Syndrome

“…In anaesthetized piglets, the nonspecific inhibition of all neurons in the rostral medullary raphé (by focal dialysis of the GABA A receptor agonist muscimol) causes a prolonged duration of apnea in the LCR (152). The LCR is also exaggerated in neonatal piglets and rats, whose body temperature rises 1–3°C above normal (150) (Figure 6). In piglets, the hyperthermic exaggeration of the LCR is most striking under postnatal day 5 and disappears by postnatal day 20 (151).…”

My child cannot breathe while sleeping: a report of three cases and review

“…The LCR protects the subglottic airway from the liquid materials and the lungs from aspiration; this reflex consists of swallowing, coughing, and arousal aimed at limiting the duration of contact between the liquids and the laryngeal mucosa [13, 14]. However, in some infants, the laryngospasm triggered by LCR and associated with nocturnal symptoms, including central or mixed/obstructive apnea, oxygen desaturation, and bradycardia due to a vagal efferent component during the sleep, can be life-threatening.…”