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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD010993-17
Application #
3485022
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1977-09-30
Project End
1994-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
17
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Thach, B T; Kenney-Hunt, J P; Simon, T C et al. (2009) Sex-specific quantitative trait loci linked to autoresuscitation failure in SWR/J mice. Heredity (Edinb) 103:469-75
Song, Z; Harris, K A; Thach, B T (2009) Laryngeal constriction during hypoxic gasping and its role in improving autoresuscitation in two mouse strains. J Appl Physiol (1985) 106:1223-6
Thach, Bradley T (2009) Does swaddling decrease or increase the risk for sudden infant death syndrome? J Pediatr 155:461-2
Thach, Bradley T (2008) Some aspects of clinical relevance in the maturation of respiratory control in infants. J Appl Physiol 104:1828-34
Thompson, John M D; Thach, Bradley T; Becroft, David M O et al. (2006) Sudden infant death syndrome: risk factors for infants found face down differ from other SIDS cases. J Pediatr 149:630-633
Scheers-Masters, Joshua R; Schootman, Mario; Thach, Bradley T (2004) Heat stress and sudden infant death syndrome incidence: a United States population epidemiologic study. Pediatrics 113:e586-92
Paluszynska, Dorota A; Harris, Kathleen A; Thach, Bradley T (2004) Influence of sleep position experience on ability of prone-sleeping infants to escape from asphyxiating microenvironments by changing head position. Pediatrics 114:1634-9
Kahraman, Levent; Thach, Bradley T (2004) Inhibitory effects of hyperthermia on mechanisms involved in autoresuscitation from hypoxic apnea in mice: a model for thermal stress causing SIDS. J Appl Physiol 97:669-74
Unger, Benjamin; Kemp, James S; Wilkins, Davida et al. (2003) Racial disparity and modifiable risk factors among infants dying suddenly and unexpectedly. Pediatrics 111:E127-31
Patel, Aloka L; Paluszynska, Dorota; Harris, Kathleen A et al. (2003) Occurrence and mechanisms of sudden oxygen desaturation in infants who sleep face down. Pediatrics 111:e328-32

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