Role of gastric acid secretion in the formation of gastric lesions induced by ischemia-reperfusion

Background: Ischemia (I) followed by reperfusion (R) is known to produce gastric lesions due to generation of free radical and increase in lipid peroxidation but the role of endogenous gastric H + secretion in the formation of this injury remains unknown. In this study we induced gastric lesions by ischemia-reperfusion (I/R) and studied gastric secretory changes during healing of I/R damage in conscious rats with or without pretreatment with antisecretory drugs. Methods: I/R gastric lesions were produced in rats with chronic gastric fistula (GF) to determine gastric H ÷ secretion without and with clamping device around the celiac artery to induce I for 30 rain that was followed by 60 rain R without or with vehicle (saline, control), ranitidine (40 mg/kg i.p.) or omeprazole (20 mg/kg i.p.). Rats were killed at 1, 3, 6, 24, 48, 72 and 96 h after I/R and the area of gastric lesions was determined by planimetry and gastric biopsy samples were taken for histological assessment. Gastric blood flow (GBF) was examined by H2-gas clearance technique and gastric H + output was measured by automatic titration of gastric juice collected from GF with 0.01 N NaOH to pH 7.0. Results: Clamping of the celiac artery decreased GBF by 90% of control value but after removal of the clamp the GBF returned immediately to control level. I/R produced acute gastric erosions in the oxyntic mucosa 1 h after R, the area of which increased up to 6 h after I/R. After 18-96 h upon I/R, these lesions progressed towards the deep gastric ulcers as assessed by histology and this was accompanied by the rise in plasma gastrin. Gastric H + secretion was suppressed immediately after I and failed to recover until 12 h, returning to the control value at 48 h after I/R. Pretreatment with ranitidine or omeprazole attenuated the acute lesions induced by I/R by about 88 and 67%, respectively, and increased GBF and plasma gastrin as compared to vehiclecontrols. Administration of antisecretory drugs 1 h after I/R, accelerated significantly healing of acute I/R lesions and completely prevented the progression of these erosions into chronic gastric ulcers and this prevention was abolished by addition of exogenous 0.1N HC1 (2 ml/day) into the stomach in rats treated with ranitidine or omeprazole. Conclusions: 1) Endogenous gastric H ÷ secretion plays an important role in progression of I/R lesions to chronic gastric ulcers; 2) Suppression of gastric acid by antisecretory drugs enhances healing of acute erosive gastritis caused by I/R and 3) Gastric ischemia enhances the release of gastrin that might contribute to the restoration of gastric acid as well as the prevention by gastric H ÷ inhibitors of progression of acute lesions into chronic ulcers.