Lower esophageal sphincter augmentation by endoscopic injection of dextranomer hyaluronic acid copolymer in a porcine gastroesophageal reflux disease model

Abstract

BackgroundWe previously demonstrated feasibility, safety, and a reproducible histologic bulking effect after injection of dextranomer hyaluronic acid copolymer (DxHA) into the gastroesophageal junction of rabbits. In the current study, we investigated the potential for DxHA to augment the lower esophageal sphincter (LES) in a porcine model of gastroesophageal reflux disease (GERD). MethodsTwelve Yucatan miniature pigs underwent LES manometry and 24-hour ambulatory pH monitoring at baseline, after cardiomyectomy, and 6weeks after randomization to endoscopic injection of either DxHA or saline at the LES. After necropsy, the foregut, including injection sites, was histologically examined. ResultsPigs in both groups had similar weight progression. Cardiomyectomy induced GERD in all animals, as measured by a rise in the median % of time pH <5 from 0.6 to 11.6 (p=0.02). Endoscopic injection of DxHA resulted in a higher median difference in LES length (1.8cm vs. 0.4cm, p=0.03). In comparison with saline injection, DxHA resulted in 120% increase in LES pressure, and 76% decrease in the mean duration of reflux episodes, but these results were not statistically significant. Injection of DxHA induced a foreign body reaction with fibroblasts and giant cells. ConclusionsPorcine cardiomyectomy is a reproducible animal GERD model. Injection of DxHA may augment the LES, offering a potential therapeutic effect in GERD.