Effect of isosorbide dinitrate on gastroesophageal reflux in healthy volunteers and patients with Chagas' disease

Abstract

The effect of isosorbide dinitrate (ISD) on gastroesophageal reflux and gastric emptying during the 24-min period following a liquid meal was studied in healthy volunteers, Chagas' disease patients with normal esophageal motility (CD-1 group), and Chagas' disease patients with esophageal dysmotility (CD-2 group) with dynamic scintigraphy. At random, on two separate days, the subjects received 5 mg isosorbide dinitrate or an identical-appearing placebo tablet, by the sublingual route, and ingested a liquid test meal containing [^99mTc]phytate colloid before scintigraphic studies were performed. Gastroesophageal reflux episodes were more frequent (P=0.016) and gastroesophageal reflux indexes were greater (P<0.010) after isosorbide dinitrate than after placebo in CD-2 group (N=15) but not in healthy volunteers (N=14) or CD-1 group (N=9); six of seven CD-2 patients presenting with gastroesophageal reflux after isosorbide dinitrate had abnormal clearance of refluxate. Gastric emptying was similar in healthy volunteers (N=13), CD-1 patients (N=6), and CD-2 patients (N=13), and no effect of isosorbide dinitrate on it was detected in any of the groups. In separate studies, 5 mg isosorbide dinitrate reduced the lower esophageal pressure (P<0.01) in seven CD-2 patients. These results indicate that ISD increases the tendency towards GER in CD-2 patients, but not in healthy volunteers or CD-1 patients. This effect is probably related to an exceedingly intense relaxation of the LES caused by ISD in CD-2 patients. Considering the role of the destruction of the intramural neurons in the pathogenesis of the esophageal motor disorder in Chagas' disease, these findings are likely to be a consequence of the loss of the normal neural influences on the lower esophageal sphincter in Chagas' disease.