Muscimol dialysis in the rostral ventral medulla reduced the CO2 response in awake and sleeping piglets

Abstract

Some victims of sudden infant death syndrome have arcuate nucleus abnormalities. The arcuate nucleus may be homologous with ventral medullary structures in the cat known to be involved in the control of breathing and the response to systemic hypercapnia. We refer to putative arcuate homologues in the piglet collectively as the rostral ventral medulla (RVM). We inhibited the RVM in awake and sleeping, chronically instrumented piglets by microdialysis of the GABAA receptor agonist muscimol. Muscimol dialysis (10 and 40 mM) had no effect on eupnea but caused a significant reduction in the response to hypercapnia during both wakefulness (34.8 ± 8.7 and 30.7 ± 10.1%, respectively) and sleep (36.7 ± 6.7 and 49.5 ± 8.9%, respectively). The effect of muscimol on the CO2 response was entirely via a reduction in tidal volume and appeared to be greater during non-rapid-eye-movement sleep. We conclude that the piglet RVM contains neurons of importance in the response to systemic CO2 during both wakefulness and non-rapid-eye-movement sleep. We hypothesize that dysfunction of homologous regions in the human infant could lead to impaired ability to respond to hypercapnia, particularly during sleep, which could potentially be involved in the pathogenesis of sudden infant death syndrome.