Ontogenic studies of gastrointestinal function. II. Lower esophageal sphincter maturation in neonatal beagle puppies

Summary: The purpose of the present study was to investigate the postnatal development of lower esophageal spincter (LES) competence in the beagle and to determine the role of gastrin in LES functional ontogeny. Eleven beagle puppies taken from two litters were studied. All puppies were allowed to suckle during the first 3 postnatal wk. In the 4th wk, all puppies were weaned, and by the 5th wk only solid chow was offered. Intraluminal manometric pressure determinations were obtained in unanesthetized, unsedated puppies using twin-lumen, 1.7 mm OD, 1 mm ID polyvinyl catheters. A 12–15 min baseline period of intraluminal pressure was monitored, after which the puppies received successive doses of 0.03, 0.1, 1.0, and 8.0 μg/kg pentagastrin (PG) SC spaced at 45-min intervals. Progressive increases in LES pressure both during basal periods and during gastric contractions and in gastric fundus (GF) pressures during gastric contractions occurred during the 1st 5 weeks of life. An increase in pressure gradient between the LES and GF during gastric contraction occurred from birth through 5 wk of age. There was no response to 0.1–8.0 μg/kg PG until postnatal days 5–6 when the LES pressure gradient in the basal state increased in response to each of these doses. There was also no significant response by the LES to PG during gastric contraction until days 11–12 when all doses of PG evoked enhancement of LES pressure. These studies suggest that an increase in LES-GF intraluminal pressure gradient develops during the initial 2 postnatal wk in this species and that this development does not involve the hormone gastrin. Later, however, the pressure gradient may depend upon both age and gastrin since a two-way analysis of variance indicated that not only is LES pressure affected by postnatal age and by PG dose, but that there is an interaction between postnatal age and PG dose which is significant. By the fifth wk, there was an apparent dose-response effect in which the lower two doses produced increased LES pressure and the larger two doses produced decreased LES pressures. Speculation: Gastroesophageal reflux (GER) in some infants may occur when the developmental interplay between endogenous gastrin concentration, increasing sensitivity to gastrin by LES, and sensitivity to gastrin by the muscular stomach proceeds abnormally. Alternatively, either the postnatal increase in LES muscle mass or the maturation of a neural pathway that mediates reflex contraction of the LES during gastric contraction, or both, may be delayed or abnormal in some children with GER. A fourth possible abnormality that may permit GER in still other infants is failure to generate the increasing gastric contraction rate and intraluminal pressures observed to occur in normal development, thus permitting delayed gastric emptying.