title: Pepsinogen release and acid secretion from human and guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness.
abstract: Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.
authors.affiliation: Dept. of Surgery, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: I M
authors.initials: IM
authors.lastname: Modlin
authors.forename: M D
authors.initials: MD
authors.lastname: Basson
authors.forename: T E
authors.initials: TE
authors.lastname: Adrian
authors.forename: J
authors.initials: J
authors.lastname: Sussman
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D006168:Guinea Pigs; D006801:Humans; D007362:Intensive Care Units; D008854:Microscopy, Electron; D010435:Pepsinogens / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D010435:Pepsinogens