New Insights into Impairment of Mucosal Defense in Portal Hypertensive Gastric Mucosa

Overview

Journal J Gastrointest Surg

Specialty Gastroenterology

Date 2000 Nov 15

PMID 11077319

Citations 2

Authors

M Tomikawa

Y Akiba

J D Kaunitz

H Kawanaka

K Sugimachi

I J Sarfeh

A S Tarnawski

Affiliations

Soon will be listed here.

Abstract

Portal hypertension (PHT) increases susceptibility of the gastric mucosa to injury. The aim of this study was to investigate whether PHT affects rat gastric mucosal defense mechanisms in vivo at the pre-epithelial, epithelial, and/or post-epithelial levels. PHT was produced in rats by staged portal vein ligation and sham-operated (SO) rats served as controls. The gastric mucosa was exposed, chambered, and continuously superfused with buffers under in vivo microscopy. We measured gastric mucosal gel layer thickness, surface epithelial cell intracellular pH (pHi), mucosal blood flow, and mucosal/serosal oxygenation. In PHT rats, gastric mucosal gel layer thickness was significantly reduced (88 +/- 16 microm in PHT rats vs. 135 +/- 25 microm in SO rats; P <0.0001), and the surface epithelial cell pHi was significantly decreased (6.80 +/- 0.11 in PHT rats vs. 7.09 +/- 0.21 in SO rats; P <0.01). Although total gastric mucosal blood flow was significantly increased in PHT rats by 72% (P <0.05), the oxygenation of the gastric mucosal surface was decreased by 42% (P <0.05) compared with SO rats. PHT impairs pre-epithelial (mucosal gel layer thickness), epithelial (pHi), and post-epithelial (maldistribution of blood flow) components of the gastric mucosal barrier. These findings can explain the increased susceptibility of portal hypertensive gastric mucosa to injury.

Citing Articles

Changes of Intestinal Functions in Liver Cirrhosis.

Fukui H, Wiest R Inflamm Intest Dis. 2018; 1(1):24-40.

PMID: 29922655 PMC: 5988129. DOI: 10.1159/000444436.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy.

Gjeorgjievski M, Cappell M World J Hepatol. 2016; 8(4):231-62.

PMID: 26855694 PMC: 4733466. DOI: 10.4254/wjh.v8.i4.231.

References

Pique J, Pizcueta P, Perez Ayuso R, Bosch J . Effects of propranolol on gastric microcirculation and acid secretion in portal hypertensive rats. Hepatology. 1990; 12(3 Pt 1):476-80. DOI: 10.1002/hep.1840120305. View

Ishikawa T, Sarfeh I, Tarnawski A, Golshan R, Douglas T, Sugiyama M . Epidermal growth factor protects portal hypertensive gastric mucosa in ischemia/reperfusion: the role of capillary endothelia and prostaglandins. Surgery. 1992; 112(2):341-6. View

Nishizaki Y, Kaunitz J, Oda M, Guth P . Impairment of gastric mucosal defenses measured in vivo in cirrhotic rats. Hepatology. 1994; 20(2):445-52. View

Vorobioff J, Bredfeldt J, Groszmann R . Hyperdynamic circulation in portal-hypertensive rat model: a primary factor for maintenance of chronic portal hypertension. Am J Physiol. 1983; 244(1):G52-7. DOI: 10.1152/ajpgi.1983.244.1.G52. View

Palmer R, Ashton D, Moncada S . Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988; 333(6174):664-6. DOI: 10.1038/333664a0. View

Wallace J, Granger D . The cellular and molecular basis of gastric mucosal defense. FASEB J. 1996; 10(7):731-40. DOI: 10.1096/fasebj.10.7.8635690. View

Sarfeh I, Soliman H, Waxman K, Coccia M, Rypins E, Bui H . Impaired oxygenation of gastric mucosa in portal hypertension. The basis for increased susceptibility to injury. Dig Dis Sci. 1989; 34(2):225-8. DOI: 10.1007/BF01536055. View

Whittle B, Moncada S . Nitric oxide: the elusive mediator of the hyperdynamic circulation of cirrhosis?. Hepatology. 1992; 16(4):1089-92. DOI: 10.1002/hep.1840160437. View

Nishizaki Y, Guth P, Kaunitz J . Isoproterenol enhances rat gastric mucosal barrier function in vivo. Gastroenterology. 1993; 105(2):340-6. DOI: 10.1016/0016-5085(93)90706-i. View

10.

Hills B, Butler B, Lichtenberger L . Gastric mucosal barrier: hydrophobic lining to the lumen of the stomach. Am J Physiol. 1983; 244(5):G561-8. DOI: 10.1152/ajpgi.1983.244.5.G561. View

11.

McCormack T, Sims J, Eyre-Brook I, Kennedy H, Goepel J, Johnson A . Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy?. Gut. 1985; 26(11):1226-32. PMC: 1432906. DOI: 10.1136/gut.26.11.1226. View

12.

Ohta M, Tanoue K, Tarnawski A, Pai R, Itani R, Sander F . Overexpressed nitric oxide synthase in portal-hypertensive stomach of rat: a key to increased susceptibility to damage?. Gastroenterology. 1997; 112(6):1920-30. DOI: 10.1053/gast.1997.v112.pm9178684. View

13.

Ichikawa Y, Tarnawski A, Sarfeh I, Ishikawa T, Shimada H . Distorted microangioarchitecture and impaired angiogenesis in gastric mucosa of portal hypertensive rats. Gastroenterology. 1994; 106(3):702-8. DOI: 10.1016/0016-5085(94)90705-6. View

14.

Sarfeh I, JULER G, STEMMER E, MASON G . Results of surgical management of hemorrhagic gastritis in patients with gastroesophageal varices. Surg Gynecol Obstet. 1982; 155(2):167-70. View

15.

Whittle B . Thirteenth Gaddum Memorial Lecture. Neuronal and endothelium-derived mediators in the modulation of the gastric microcirculation: integrity in the balance. Br J Pharmacol. 1993; 110(1):3-17. PMC: 2175995. DOI: 10.1111/j.1476-5381.1993.tb13763.x. View

16.

Pique J, Leung F, Kitahora T, Sarfeh I, Tarnawski A, Guth P . Gastric mucosal blood flow and acid secretion in portal hypertensive rats. Gastroenterology. 1988; 95(3):727-33. DOI: 10.1016/s0016-5085(88)80021-0. View

17.

Kim H, Kim K . Effect of nitric oxide on hydrogen peroxide-induced damage in isolated rabbit gastric glands. Pharmacology. 1998; 57(6):323-30. DOI: 10.1159/000028258. View

18.

Hashizume M, Tanaka K, Inokuchi K . Morphology of gastric microcirculation in cirrhosis. Hepatology. 1983; 3(6):1008-12. DOI: 10.1002/hep.1840030619. View

19.

Ferraz J, Tigley A, Wallace J . Paradoxical effects of L-arginine on gastric mucosal integrity. Eur J Pharmacol. 1994; 260(1):107-11. DOI: 10.1016/0014-2999(94)90018-3. View

20.

Arakawa T, Tarnawski A, Mach T, Kobayashi K, Sarfeh I . Impaired generation of prostaglandins from isolated gastric surface epithelial cells in portal hypertensive rats. Prostaglandins. 1990; 40(4):373-82. DOI: 10.1016/0090-6980(90)90102-2. View