Impairment of Acid-Neutralizing Capacity and Lesion Formation in the Rat Duodenum during Hemorrhagic Shock: Comparative Study with Indomethacin

Abstract

Abstract-The effects of hemorrhagic shock (HE) on duodenal pH, acid-neutralizing capacity and mucosal tolerance to acid were investigated in anesthetized rats, and they were compared with those of indomethacin. HE was performed by bleeding from the carotid artery to reduce arterial blood pressure to about 55 mmHg (3 ml of bleeding per 200 g of body weight), and indomethacin was given s.c. in a dose of 5 mg/kg. Duodenal pH was determined in the outflow from the proximal duodenum (1.7 cm) which was perfused with 10-4 M HCI, and acid-neutralizing capacity was measured by back-titration of the perfusate to pH 4.0 with 10 mM HCI. Under these conditions, duodenal pH was kept at around 6.0 as the result of neutralization in the loop (-8 ,uEq/hr). Both HE and indomethacin significantly decreased the pH and acid-neutralizing capacity. Administration of 16,16 dimethyl prostaglandin E2 (16-dmPGE2: 30 ,ag/kg, s.c.) significantly increased both pH and acid-neutralizing capacity in normal and indomethacin-treated rats, but failed to affect these parameters in rats under HE conditions. When the duodenal loop was perfused with 50 mM HCI for 1.5 hr, both HE and indomethacin induced extensive damage in the mucosa. Pretreatment with 16-dmPGE2 sig nificantly reduced the formation of duodenal lesions induced by indomethacin but not by HE. These results suggest that HE as well as indomethacin impaired duodenal acid-neutralizing capacity to reduce the tolerance to acid of the mucosa. The deleterious effects of H E on the mucosa may be mainly due to a decreased mucosal blood flow, but not due to a deficiency of endogenous prostaglandins.

Stimulation by Prostaglandin E2 of Alkaline Secretion in the Rat Duodenum: Comparative Study with Hypertonic NaCI

“…The duodenal PD was determined using a PD meter (Yokokawa, Type 2575) through two agar bridges, one positioned in the lumen of the duodenum and the other in the abdominal cavity (6). The pH of the duodenal perfusate was measured using a pH glass electrode of the flow type (Horiba, Model 6901-25T), and continuously monitored on a two channel recorder (Hitachi, Model 056), simultaneously with the duo denal PD.…”