Role of inhibitory neurotransmitter interactions in the pathogenesis of neonatal apnea: implications for management.

F H p T A b l © 0 pnea of prematurity remains a troublesome clinical problem in the care of low birth eight infants. It may significantly impact the neoatal course of such patients by necessitating the se of assisted ventilation, prolonging their hospialization, and resulting in a need for xanthine or ther pharmacologic intervention. To better unerstand the physiologic basis for neonatal apnea, he response of respiratory neural output to hyperapnia, hypoxia, and stimulation of laryngeal and ther mechanoreceptor-mediated afferents has een extensively studied in both human infants nd various animal models. However, maturation f the role of neurotransmitters that mediate these eural pathways at the brainstem is poorly undertood. As fetal and early neonatal life are characerized by greater inhibition of respiratory output han in later life, it is tempting to speculate that his period is associated with greater expression of nhibitory versus excitatory neurotransmitters and euromodulators in respiratory-related neurons. A ariety of such substances have been implicated in eonatal respiratory control and some, such as erotonin and adenosine, may have excitatory or nhibitory effects depending on the receptor subypes activated (Fig 1). Although prostaglandins nd endorphins have both been studied for their ole as inhibitory neurotransmitters in relation to eonatal respiratory control,1 the focus of this reiew will be on gamma aminobutyric acid (GABA), denosine, and their potential interaction as the ajor modulators of respiratory neural output in arly life.