The effects of a GABA(A) agonist in the rostral ventral medulla on sleep and breathing in newborn piglets

Study Objectives: Abnormalities in the rostral ventral medulla (RVM) in hum an infants may contribute to the etiology of the sudden infant death syndro me (SIDS) or a subset of SIDS, by interfering with cardiorespiratory and ar ousal responses to physiological stimuli often encountered during sleep. Th e purpose of this study was to determine whether inhibition of groups of ne urons in the RVM in newborn piglets would alter steep and/or the sleep-modu lation of breathing. We hypothesized that inhibition of neurons in the RVM would produce less wakefulness or increase the low frequency power (delta) during Quiet sleep. Design: Unanesthetized piglets were studied in a whole-body plethysmograph. Artificial cerebral spinal fluid (aCSF) or the GABAA agonist, muscimol, wa s dialyzed into the RVM for 40 minutes after a control period consisting of aCSF dialysis. Sleep was analyzed using a combination of EEG spectral anal ysis and behavioral observations. Setting: N/A Participants: N/A Interventions: N/A Measurements and Results: Cardiorespiratory variables varied with state. Di alysis of neither aCSF nor muscimol into the RVM resulted in alterations in resting respiration, BP, HR, or VO2 or their modulation by state. Compared to control dialysis with aCSF, muscimol dialysis caused dramatic effects o n sleep architecture. Sleep cycling was abolished in some experiments, wher eas in others there were decreases in low-frequency EEG activity or delta p ower. The animals in which sleep cycling ceased continued in a perpetual st ate of drowsiness interspersed with periods of wakefulness. Conclusions: We conclude that dialysis of muscimol into the RVM has little effect on resting breathing, blood pressure, or heart rate or their modulat ion by state, but interferes with normal sleep architecture. We speculate t hat abnormalities in the ventral medulla may alter sleep cycling or interfe re with arousal mechanisms, thus contributing to the etiology of at least a subset of SIDS.