Weakness of mucosal barrier in portal hypertensive gastropathy of alcoholic cirrhosis. Effects of propranolol and enprostil.
OBJECTIVE
It has been suggested that the vulnerability of gastric mucosa is increased in patients with cirrhosis as a result of a PGE2 deficiency. Therefore, we evaluated whether PGE2 mucosal generation, and gastric potential difference - a reflection of the gastric mucosal barrier - were correlated to endoscopic features and whether these alterations could be alleviated.


METHODS
The potential difference was measured before (basal) and after a stimulation test by aspirin. The serum levels of gastrin and glucagon were also determined. Finally, the effects of a 1-week administration of propranolol or enprostil were tested on potential difference. The endoscopic grade of portal hypertensive gastropathy was assessed according to McCormack et al. The results are presented respectively for controls, patients with mild gastropathy, and patients with severe gastropathy. Comparisons were made using variance or covariance analysis after adjustment with age.


RESULTS
Basal potential difference was significantly different between the three groups: -30.6, -28.8, -24.9 mV, p <0.05, respectively. The effects of aspirin administration on potential difference parameters were significantly different between the three groups (irritability index: 35 +/- 25, 92 +/- 98, 114 +/- 74 mV2.min, p <0.05, respectively) when non-responders to aspirin were excluded. PGE2 mucosal generation was significantly increased in both the antrum (9.8, 19.5, 19.7 ng/mg proteins, p<0.05, respectively) and in the corpus (8.1, 14.0, 20.2 ng/mg proteins, p<0.05, respectively). PGE2 generation was not related to potential difference. Glucagon serum levels were related to the grade of gastropathy. A 1-week administration of 160 mg/d long-acting propranolol, 35 micro g/d enprostil or placebo did not significantly modify basal potential difference.


CONCLUSIONS
Portal hypertensive gastropathy is characterized by a decreased potential difference proportional to the endoscopic severity. The gastric mucosa of patients with cirrhosis seems to be more susceptible to aspirin than that of healthy subjects. It appears that the role of PGE2 is controversial in portal hypertensive gastropathy. Propranolol and enprostil do not improve this decreased potential difference.
Payen
J L
JL
Service d'Hepato-Gastroenterologie, CHU Purpan, Toulouse, France.
Cales
P
P
Pienkowski
P
P
Sozzani
P
P
Kervran
A
A
Frexinos
J
J
Pascal
J P
JP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects; D015232:Dinoprostone / Q000502:physiology; D016620:Enprostil / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000503:physiopathology; D005755:Gastrins / Q000097:blood; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications / Q000503:physiopathology*; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology*; D013272:Stomach Diseases / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D000897:Anti-Ulcer Agents; D005755:Gastrins; D011433:Propranolol; D016620:Enprostil; D015232:Dinoprostone; D001241:Aspirin