Impact of acid and pepsin on human esophageal prostaglandins.

OBJECTIVES

Although the prostaglandin-mediated mucosal protection within the gastric compartment has been well established, its potential role in the maintenance of integrity of the esophageal mucosa in humans has not been explored due to the lack of appropriate methodology.

METHODS

We have recently developed an esophageal perfusion catheter, equipped with two balloons, compartmentalizing a 7.5-cm segment of the esophageal lumen. Using this catheter, we studied the impact of the luminal perfusion with saline, HCl (0.01 M, pH 2.1), and HCl/pepsin solutions (0.5 mg/ml) on esophageal luminal release of PGE2 in 21 asymptomatic, presumably healthy volunteers (12 M, 9F; mean age 40 yr). The content 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

Perfusion 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 +/- 640 pg/min during the second 8-min perfusion period. This rate declined (although in nonsignificant fashion; p < 0.2) during the third perfusion period, reaching a plateau of 1220 +/- 473 pg/min and maintained during the last (period IV) perfusion period with saline. Introduction of acid during the perfusion period II in the second group of investigated 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 next 8-min perfusion period further diminished the luminal release of PGE2 to the value of 520 +/- 73; p < 0.001. The significant decline in the rate of luminal PGE2 release was still maintained despite the replacement of acid with saline during the ending 8-min perfusion (period IV; 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 than 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 the 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 and pepsin.

CONCLUSION

The modulatory effect of acid and pepsin on esophageal mucosal prostaglandin release may play a role in the development of reflux-related mucosal pathology.