Relationship between low-dose aspirin-induced gastric mucosal injury and intragastric pH in healthy volunteers.
OBJECTIVE
Gastric acid plays an important role in the pathogenesis of gastric mucosal lesions. We investigated whether aspirin-induced gastric mucosal injury might have any association with the intragastric pH.


METHODS
Fifteen healthy, Helicobacter pylori-negative volunteers randomly underwent the four different 7-day regimens: (1) aspirin 100 mg, (2) rabeprazole 10 mg, (3) aspirin 100 mg + rabeprazole 10 mg, and (4) aspirin 100 mg + rabeprazole 40 mg. Gastric mucosal injury based on the modified Lanza score (MLS), 24-h intragastric pH, and histopathology of gastric mucosa were evaluated prior to the start and on day 7 of each regimen.


RESULTS
The median MLSs were 0 in the baseline and the rabeprazole 10 mg regimen. The median MLS in the aspirin regimen was 3, while those in both aspirin + rabeprazole 10 mg and aspirin + rabeprazole 40 mg regimens were 0. Rabeprazole significantly prevented the gastric mucosal injury by aspirin (P = 0.001 for rabeprazole 10 mg and P = 0.005 for rabeprazole 40 mg). The MLSs were negatively correlated with the 24-h intragastric pH (P = -0.711, < 0.001), whereas aspirin had no effect on the intragastric pH. Aspirin expanded the mean diameter of the microvessels of the gastric mucosa, which, in turn, was negatively correlated with the intragastric pH.


CONCLUSIONS
Aspirin might induce gastric mucosal injury by affecting the mucosal microvessels in an acid-dependent manner. Sustained maintenance of the intragastric pH at an elevated value is necessary to prevent gastric mucosal damage induced by aspirin.
Nishino
Masafumi
M
First Department of Medicine, Hamamatsu University School of Medicine, Higashi-Ku, Hamamatsu, Japan.
Sugimoto
Mitsushige
M
Kodaira
Chise
C
Yamade
Mihoko
M
Shirai
Naohito
N
Ikuma
Mutsuhiro
M
Tanaka
Tatsuo
T
Sugimura
Haruhiko
H
Hishida
Akira
A
Furuta
Takahisa
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D001706:Biopsy; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005773:Gastroscopy; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010641:Phenotype; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000378:metabolism; D064750:Rabeprazole; D012720:Severity of Illness Index; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D001241:Aspirin