Mechanisms of gastro-oesophageal reflux in the ferret

Abstract

Transient lower oesophageal sphincter (LOS) relaxation is the major mechanism of gastro-oesophageal reflux in humans--an event unassociated with swallowing. Mechanisms involved in triggering transient LOS relaxation are poorly understood, and their further study requires a small animal model. In this study we aimed to establish methods for prolonged ambulant oesophageal manometry in ferrets, and to determine motor events associated with reflux episodes and their triggering by different gastric nutrient loads. Forty-two studies were performed on nine ferrets with chronic cervical oesophagostomies, through which a manometric assembly was introduced and secured to a collar, which incorporated a microphone for detection of swallows. The assembly included a gastric feeding channel, one gastric and four oesophageal manometric sideholes, 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 mL air (nine studies). Episodes of oesophageal acidification were absent before gastric infusions. After infusion, 2.1 +/- 0.2 episodes occurred over the first 30 min. After glucose infusion, 15/18 acidification episodes (83%) occurred during transient LOS relaxation, and 3/18 (17%) occurred after gradual (< 1 mmHg sec-1) downward drifts in basal LOSP to < 2 mmHg. After lipid infusion two acidification episodes occurred, both during transient LOS relaxation. Mean duration of transient LOS relaxation was 8.0 +/- 0.4 sec. All infusions increased occurrence of transient LOS relaxation to a similar extent, each of which ended with primary peristalsis. We conclude that gastric infusion of glucose, lipid and gas are all effective in provoking gastro-oesophageal reflux in ferrets. Reflux occurs through similar mechanisms to those seen in humans, i.e. increased triggering of transient LOS relaxation. The conscious ferret is therefore an appropriate model for future studies of manipulation of mechanisms giving rise to gastro-oesophageal reflux.