Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals

Abstract

Jadcherla SR, Parks VN, Peng J, Dzodzomenyo S, Fernandez S, Shaker R, Splaingard M. Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals. Am J Physiol Gastrointest Liver Physiol 302: G134 -G144, 2012. First published August 18, 2011 doi:10.1152/ajpgi.00067.2011 as an effect of visceral provocation or of its temporal relationships with aerodigestive reflexes in premature neonates is not known. We tested the hypothesis that esophageal provocation results in both esophageal reflex responses and ECAs during sleep and that ECAs are dependent on the frequency characteristics of esophageal neuromotor responses. We defined the spatiotemporal relationship of ECAs in relation to 1) spontaneous pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and 2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy premature neonates born at 27.9 Ϯ 3.4 wk were tested at 36.8 Ϯ 1.9 wk postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in sleep during concurrent manometry and videopolysomnography. With stimulus onset as reference point, we scored the response latency, frequency occurrence and duration of arousals, peristaltic reflex, and upper esophageal sphincter contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and esophageal sensory-motor parameters were scored by blinded observers. Significantly (for each characteristic listed, P Ͻ 0.05), swallow sequences were associated with arousals and sleep state changes, and arousals were associated with incomplete peristalsis, response delays to lower esophageal sphincter relaxation, and prolonged esophageal clearance. GER events (73.5%) provoked arousals, and arousals were associated with response delays to peristaltic reflexes or clearance, sleep state modification, and prolonged respiratory arousal. Midesophageal stimuli (54%) provoked arousals and were associated with increased frequency, prolonged latency, prolonged response duration of peristaltic reflexes and UESCR, and increased frequency of sleep state changes and respiratory arousals. In human neonates, ECAs are provoked upon esophageal stimulation; the sensory-motor characteristics of esophageal reflexes are distinct when accompanied by arousals. Aerodigestive homeostasis is defended by multiple tiers of aerodigestive safety mechanisms, and when esophageal reflexes are delayed, cortical hypervigilance (ECAs) occurs.

Maturation of upstream and downstream esophageal reflexes in human premature neonates: the role of sleep and awake states

“…These findings suggest that maturation advances the regulation of UES, esophageal body peristalsis, and LES functions during sleep. Brain stem maturation is the most likely contributing factor to the regulation of observed sensory-motor interaction patterns, with similar observations reported through maturation of the central pattern generator and the respiratory rhythm regulation apparatus (4,5,22,26,35). We speculate that appropriate regulation of esophageal peristalsis and sphincteric functions protect the proximal aerodigestive tract against retrograde threats such as GER events during sleep.…”

“…These findings again implicate development of appropriate local sensory-motor interactions and adaptive regulatory abilities during sleep, favoring increased occurrence of SP in healthy thriving premature infants. The occurrence of EDR can coactivate multiple neural pathways modifying respiratory rhythm and deglutition apnea during swallowing (20,22). Such regulation appears present in premature infants during sleep.…”

Behavioral Observation Differentiates the Effects of an Intervention to Promote Sleep in Premature Infants

“…Gastroesophageal reflux has been associated with disrupted sleep in children younger than a year of age, 19 and it gives rise to arousals in neonates. 20 As we are a surgical NICU, infants with gastrointestinal diagnosis, such as gastrointestinal obstruction, gastroschisis, and necrotizing enterocolitis, are a high proportion of our population, and some require surgery. The impact of surgery on sleep was a potential factor that could impact study outcomes.…”

Physiology of esophageal sensorimotor malfunctions in neonatal neurological illness

“…We have recently developed and validated multimodal esophageal provocative methods to examine the functions of vagal afferent and efferent pathways by defining sensorimotor characteristics of esophageal body, UES contractile reflexes, and LES relaxation reflexes in healthy human neonates (7,8,11,12,24). Specifically, mechanosensitive, osmosensitive, and chemosensitive provocation of the midesophagus was undertaken using air, water (pH 7.0), and apple juice (pH 3.7), respectively, and the effects on upstream (UES) and downstream (LES) reflexes and esophageal peristalsis were evaluated.…”

“…Specifically, mechanosensitive, osmosensitive, and chemosensitive provocation of the midesophagus was undertaken using air, water (pH 7.0), and apple juice (pH 3.7), respectively, and the effects on upstream (UES) and downstream (LES) reflexes and esophageal peristalsis were evaluated. By using these media in graded incremental volumes, we defined the responses to varying physical and chemical characteristics of stimulus, media, and volume (12,25). During GER events, physical and chemical characteristics of the refluxate provoke the esophagus.…”