MECHANISMS OF GASTROESOPHAGEAL REFLUX IN THE FERRET

Transient lower oesophageal sphincter (LOS) relaxation is the major me chanism of gastro-oesophageal reflux in humans - an event unassociated with swallowing. Mechanisms involved in triggering transient LOS rela xation are poorly understood, and their further study requires a small animal model. In this study we aimed to establish methods for prolong ed ambulant oesophageal manometry in ferrets, and to determine motor e vents associated with reflux episodes and their triggering by differen t gastric nutrient loads. Forty-two studies were performed on nine fer rets with chronic cervical oesophagostomies, through which a manometri c assembly was introduced and secured to a collar, which incorporated a microphone for detection of swallows. The assembly included a gastri c feeding channel, one gastric and four oesophageal manometric sidehol es, a 2.5-cm-long LOS sleeve sensor, and an oesophageal pH electrode. Intragastric infusions were given over 2 min, the first after a 30-min control recording period, and in 29/42 studies, a second infusion was given 60 min later. Infusions were either 25 mL 10% dextrose solution , pH 3.5 (22 studies), 25 mL triglyceride emulsion (Intralipid) pH 3.5 (11 studies), or 25 mt air (nine studies). Episodes of oesophageal ac idification were absent before gastric infusions. After infusion, 2.1 +/- 0.2 episodes occurred over the first 30 min. After glucose infusio n, 15/18 acidification episodes (83%) occurred during transient LOS re laxation, and 3/18 (17%) occurred after gradual (< 1 mmHg sec(-1)) dow nward drifts in basal LOSP to < 2 mmHg. After lipid infusion two acidi fication episodes occurred, both during transient LOS relaxation. Mean duration of transient LOS relaxation was 8.0 +/- 0.4 sec. All infusio ns increased occurrence of transient LOS relaxation to a similar exten t, each of which ended with primary peristalsis. We conclude that gast ric infusion of glucose, lipid and gas are all effective in provoking gastro-oesophageal reflux in ferrets. Reflux occurs through similar me chanisms to those seen in humans, i.e. increased triggering of transie nt LOS relaxation. The conscious ferret is therefore an appropriate mo del for future studies of manipulation of mechanisms giving rise to ga strooesophageal reflux.