The proposed studies concern physiologic mechanisms involved in initiation and recovery from attacks of apnea, such as occur in a variety of human diseases and disorders. Emphasis is given to maturation of the neuromuscular mechanisms that maintain patency of the upper airway. Attention is also directed to mechanisms involved in spontaneous recovery from apnea produced by acute anoxia. We plan to investigate reflex activity in rabbits during central nervous system depression produced by hypoxia. Upper airway protective reflexes and respiratory reflexes will be studied. Studies in mice will evaluate the ability to spontaneously recover form apnea and central nervous system depression produced by acute hypoxia (""""""""autoresuscitation""""""""). Specially, the affects of anesthesia and repeated anoxic exposure on respiratory gasping activity and autoresuscitation will be examined. Mice that develop an inability to autoresuscitate at the time of weaning will be studied to see if characteristic patterns in respiratory or cardiac activity predict death and if pretreatment with various agents restores viability. We will also see if increased upper airway resistance or oral obstruction decreases ability to spontaneously recover form hypoxic apnea. Animals of different ages will be evaluated in these various studies to determine maturational effects on response patterns. In human studies, we will investigate infants who habitually sleep with their nose and mouth pressed into the bedding. The prevalence of the face-directly-down sleep position, mattress composition, and sleep state will be studied. Infants with tracheostomies will be evaluated to determine the source of the cyclical pressure changes in the upper airway that appear when it is closed to the atmosphere. Such oscillations are indicative of critical airway maintaining forces. Therefore, electromyographic activity of different upper airway muscles will be surveyed to see if changes in muscle activity correspond to the oscillations. We also plan to study the effect of maturation on this airway stabilizing activity. Normal term and preterm infants will be studied to evaluate the precise timing and coordination of breathing, sucking, and swallowing during bottle feeding. In further studies, we will evaluate maturation of this coordination. Attention will be focused on the inhibition of breathing by swallows and obstruction of inspiratory efforts during swallows. In preterm and term infants who have episodes of apnea, and/or cyanosis, during feeding, we will conduct similar studies to define the pathophysiology of the apnea and its resolution with maturation.
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