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There is controversy surrounding the effects of portal hypertension on the level of perfusion to the gastric wall. This study maps the regional distribution of gastric mucosal and muscle blood flow measured using quantitative autoradiography in a carbon tetrachloride-induced rat model of hepatic cirrhosis. There was a significant increase in both corpus mucosal (124.3 +/- 13.8 vs. 84.8 +/- 4.2 ml.100 g-1.min-1) and muscle blood flow (50.9 +/- 3.6 vs. 33.4 +/- 2.3 ml.100 g-1.min-1) in animals with experimental cirrhosis compared with controls. There was no significant difference in the ratio of blood tracer concentration between the basal and luminal aspects of corpus mucosa in cirrhotic and control groups. We conclude that experimental cirrhosis is associated with gastric mucosal hyperperfusion and that "active" rather than "passive" congestion of the stomach wall may be a more appropriate description of the basic hemodynamic change in this model.

The susceptibility of the gastric mucosa to injury by topical sodium taurocholate (40 mmol/l) in hydrochloric acid (150 mmol/l) was studied in prehepatic and cirrhotic rat models of portal hypertension. Portal venous pressure was increased in rats who had undergone partial portal vein ligation compared with rats that had undergone sham operation on days 3, 7, and 28 after operation (20.6 (0.9), 14.8 (0.8), and 11.3 (0.5) mm Hg v 7.3 (0.7), 7.3 (0.6), and 8.2 (0.2) mmHg respectively (mean (SEM)). At day 3 gastric mucosal injuries were increased in rats with partial portal vein ligation compared with sham operated rats (55.3 (9.4) vs 22.3 (10.5) mm2, p = 0.006), but at the later time intervals there was no significant difference in injuries between the two groups. In rats with carbon tetrachloride induced hepatic cirrhosis, portal pressure was increased (15.6 (1.0) v 6.7 (0.6) mmHg), but again there was no significant difference in mucosal injuries relative to control animals. We conclude that gastric mucosal defence mechanisms are impaired in acute but not chronic experimental portal hypertension.

There is conflicting evidence concerning the effects of portal hypertension on the gastric mucosa. This paper summarises the histological and haemodynamic alterations which are present in both human and experimental portal hypertension. Despite the fact that histological studies suggests that the gastric mucosa is an oedematous plethoric structure in portal hypertension, haemodynamic studies show that gastric mucosal blood glow is at least maintained if not increased in portal hypertension. The term "active" rather than "passive" congestion is a more appropriate description of the basic change present in the gastric mucosa in portal hypertension.

The effects of both an H1 receptor antagonist and an H2 receptor antagonist on changes in monovalent ion flux induced by topical sodium taurocholate were studied in antrectomised dogs fashioned with a denervated fundic pouch. The magnitude of taurocholate-induced ion flux was unaffected by topical administration of H1 or H2 receptor antagonists Parenteral administration of H1 or H2 receptor antagonist given singly or in combination produced an increase in net luminal Na+ gain before taurocholate administration but failed to reduce the magnitude of taurocholate-induced ion flux. It is concluded that histamine receptors are unlikely to have a role in the induction of mucosal injury by bile salts.

Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis.

The effects of the synthetic prostaglandin 16, 16 dimethyl-E2 methyl ester (16-diMe-PGE2) and the histamine H2-receptor antagonist metiamide on the gastric mucosal barrier have been studied using the Heidenhain pouch dog model. The 16-diMe-PGE2 caused significant change in the ionic permeability of the mucosa when instilled into the pouch in a concentration of 300 mug/20 ml. Intravenous administration of 16-diMe-PGE2 did not alter the barrier nor did it alter the response of the mucosa to sodium taurocholate. Metiamide given into the pouch did not affect the mucosa barrier and the response to taurocholate was not affected when metiamide was given locally or intravenously.

The effect of varying doses of cimetidine and omeprazole, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg; 1 ml/100 g) in 0.175 M HCl or topical sodium taurocholate (40 mM; 1 ml/100 g) in 0.175 M HCl was studied in the pylorus ligated rat. Preliminary studies revealed dose dependent inhibition of acid secretion with both cimetidine and omeprazole. Intraperitoneal cimetidine 50 mg/kg and 100 mg/kg given before topical acidified aspirin reduced mucosal lesions from a control score of 23.7 +/- 3.5 (mean +/- SEM) in which 83% of stomachs contained lesions, to 6.9 +/- 2.2 and 3.5 +/- 2.1 respectively (p less than 0.05), 36% and 27% of stomachs containing lesions. A dose of 250 mg/kg failed to reduce lesion score significantly (17.8 +/- 4.9) and 64% of stomachs contained lesions. Taurocholate-induced lesion score was reduced from a control value of 32.7 +/- 4.3 in which 97% of stomachs contained lesions to 10.8 +/- 3.3 and 15.5 +/- 3.8 by cimetidine 10 mg/kg and 25 mg/kg respectively (p less than 0.05), 62% and 68% of stomachs containing lesions. Cimetidine 50 mg/kg and 100 mg/kg failed to significantly reduce mucosal damage. Intraduodenal omeprazole (1.25 to 50 mumol/kg) given before topical acidified aspirin or taurocholate failed to reduce mucosal lesions, as did intragastric omeprazole 5 mumol/kg and 50 mumol/kg given before acidified aspirin. Cimetidine showed cytoprotective properties over a specific dose range beyond which the effect was lost despite continuing suppression of acid secretion. Omeprazole exhibited no cytoprotective activity.

The histamine H2-receptor antagonist, cimetidine, when given topically or parenterally, did not affect net luminal Na+ gain or net luminal H+ loss in vagally-denervated pouches of antrectomised dogs. Cimetidine did not affect disruption of the mucosal barrier by 5 mmol/l or 20 mmol/l sodium taurocholate.

15(R)-methyl PGE2 methyl ester (15MPG) and 16,16-dimethyl PGE2 methyl ester (16DMPG) were assessed for their effect on gastric mucosal permeability to Na+ and H+ in dogs prepared by antrectomy and vagally-denervated fundic pouches. 15MPG did not increase mucosal permeability to either ion when given topically (18.75-300 microgram) or parenterally (30 microgram), and did not affect permeability increases induced by topical 5mM sodium taurocholate in acid solution. 16DMPG caused significant increases in net Na+ gain when given topically (18.75-75 microgram) but did not affect net H+ loss from the pouch lumen. Attempts to use higher doses of 16DMPG were abandoned because of bleeding from the pouch, and perforation in one animal. It is conceivable that 16DMPG could cause adverse effects on the gastric mucosal barrier if used to suppress gastric secretion therapeutically. 15MPG does not share this potentially harmful property and remains worthy of further study as an inhibitor of gastric secretion with therapeutic promise.

Iodo[14C]antipyrine autoradiography was used to measure gastric mucosal blood flow in anesthetized rats and to study regional distribution. Blood flows of 61 +/- 8 ml.100 g-1.min-1 (means +/- SE) in corpus and 84 +/- 9 ml.100 g-1.min-1 in antral mucosa compared well with previously reported measurements by hydrogen clearance. Blood flow in the crests of corpus mucosal folds was significantly higher than in the valleys between folds, indicating that the greater susceptibility of the former areas to acute injury, documented in several studies, is not associated with a perfusion defect in the resting stomach. Corpus mucosal blood flow was also higher in the side walls of the stomach than in the greater curvature region, and in distal than in proximal locations. No systematic regional variations within antral mucosa were demonstrated.