IMPACT OF ACID AND PEPSIN ON HUMAN ESOPHAGEAL PROSTAGLANDINS

Objectives: Although the prostaglandin-mediated mucosal protection wit hin the gastric compartment has been well established, its potential r ole in the maintenance of integrity of the esophageal mucosa in humans has not been explored due to the lack of appropriate methodology. Met hods: We have recently developed an esophageal perfusion catheter, equ ipped with two balloons, compartmentalizing a 7.5-cm segment of the es ophageal lumen. Using this catheter, we studied the impact of the lumi nal perfusion with saline, HCl (0.01 M, pH 2.1), and HCl/pepsin soluti ons (0.5 mg/ml) on esophageal luminal release of PGE2 in 21 asymptomat ic, presumably healthy volunteers (12 M, 9F; mean age 40 yr). The cont ent of PGE2 in its methyl oximated form was measured by RIA (Amersham, IL), using a novel iodinated label. Results are expressed as mean +/- SEM. Student's t test was used for statistical analysis. Results: Per fusion of the esophageal lumen resulted in continuous release of PGE2 into the perfusate at the rate of 1880 +/- 393 pg/min during the first 8-min perfusion period. During continuation of perfusion with saline, the luminal release of PGE2 was maintained at the rate of 1820 +/- 64 0 pg/min during the second 8-min perfusion period. This rate declined (although in nonsignificant fashion; p < 0.2) during the third perfusi on period, reaching a plateau of 1220 +/- 473 pg/min and maintained du ring the last (period IV) perfusion period with saline. Introduction o f acid during the perfusion period II in the second group of investiga ted subjects resulted in a rapid and statistically significant decline of the luminal release of PGE2 to the value of 1020 +/- 167 ng/min (p < 0.01). Continuation of esophageal perfusion with acid during the ne xt 8-min perfusion period further diminished the luminal release of PG E2 to the value of 520 +/- 73; p < 0.001. The significant decline in t he rate of luminal PGE2 release was still maintained despite the repla cement of acid with saline during the ending 8-min perfusion (period I V; 560 +/- 80 ng/min; p < 0.001). Esophageal perfusion with HCl/pepsin solution, in group III subjects, potentiated luminal release of PGE2, reaching the value of 1553 +/- 340 pg/min, which is 3 times higher th an the value of PGE2 observed during corresponding perfusion with HCl (period III; p < 0.03). This significant impact of HCl/pepsin solution was still maintained despite the substitution of HCl/pepsin with NaCl during the last perfusion period, and was still significantly higher (1260 +/- 220 pg/min; p < 0.02) than the corresponding value during th e ending perfusion with NaCl after HCl (group II). This study for the first time demonstrates that luminal release of PGE2 in humans remains under a significant impact of luminal chemical factors such as acid a nd pepsin. Conclusion: The modulatory effect of acid and pepsin on eso phageal mucosal prostaglandin release may play a role in the developme nt of reflux-related mucosal pathology.