Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomach in vitro.
Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO2 and bicarbonate whereas, during normal acid, secretion cytoprotective CO2/HCO3- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in an in vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO2 supply. Without acid inhibition there was no mucosal damage at any level of serosal CO2/HCO3- supply. Acid inhibition reduced metabolic CO2 production by 29% (P < 0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P < 0.05). Although, 1% CO2 supply completely replaced the reduction in metabolic CO2, it did not protect against mucosal damage. Overreplacement by 5% serosal CO2/HCO3- was required to prevent damage. There was no correlation between luminal CO2/HCO3- output and mucosal damage. The protection by endogenous or exogenous CO2/HCO3- appears to act intracellularly rather than by intragastric or intercellular neutralization.
Glauser
M
M
Department of Gastroenterology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Bauerfeind
P
P
Feil
W
W
Riegler
M
M
Fraser
R
R
Blum
A L
AL
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D012704:Serous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D001639:Bicarbonates; D004791:Enzyme Inhibitors; D007093:Imidazoles; C035235:Sch 28080; D002245:Carbon Dioxide; D000251:Adenosine Triphosphatases