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.

The laryngeal chemoreflex (LCR) is elicited by water in the larynx and leads to apnea and respiratory disruption in immature animals. The LCR is exaggerated by the elevation of brain temperature within or near the nucleus of the solitary tract (NTS) in decerebrate piglets. Thermal prolongation of reflex apnea elicited by superior laryngeal nerve stimulation is reduced by systemic administration of GABA(A) receptor antagonists. Therefore, we tested the hypothesis that microdialysis within or near the NTS of gabazine, a GABA(A) receptor antagonist, would reverse thermal prolongation of the LCR. We examined this hypothesis in 21 decerebrate piglets (age 3-13 days). We elicited the LCR by injecting 0.1 ml of water into the larynx before and after each piglet's body temperature was elevated by approximately 2.5 degrees C and before and after 2-5 mM gabazine was dialyzed unilaterally and focally in the medulla. Elevated body temperature failed to prolong the LCR in one piglet, which was excluded from analysis. Elevated body temperature prolonged the LCR in all the remaining animals, and dialysis of gabazine into the region near the NTS (n = 10) reversed the thermal prolongation of the LCR even though body temperature remained elevated. Dialysis of gabazine in other medullary sites (n = 10) did not reverse thermal prolongation of the LCR. Gabazine had no consistent effect on baseline respiratory activity during hyperthermia. These findings are consistent with the hypothesis that hyperthermia activates GABAergic mechanisms in or near the NTS that are necessary for the thermal prolongation of the LCR.

We investigated the interaction between body temperature and the duration of the laryngeal chemoreflex (LCR) in decerebrate piglets. Elevating body temperature by approximately 2 degrees C prolongs the duration of the LCR and the length of apnea associated with the reflex. This thermal prolongation seems to arise within the nucleus of the solitary tract in the brainstem, and we believe the thermal effect is mediated by enhanced GABAergic neurotransmission.