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Relationship Between Low-Dose Aspirin-Induced Gastric Mucosal Injury and Intragastric pH in Healthy Volunteers

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Abstract

Background and Aims

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.

Materials and 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.

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Abbreviations

COX:

Cyclooxygenase

CYP2C19:

Cytochrome P450 2C19

H. pylori :

Helicobacter pylori

IM:

Intermediate metabolizer

MLS:

Modified Lanza score

NSAID:

Non-steroidal anti-inflammatory drug

PG:

Prostaglandin

PM:

Poor metabolizer

RM:

Rapid metabolizer

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Acknowledgments

This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20590718) and (20014007) and grants from Ministry of Health, Labour and Welfare (19-19). The abstract of the study was presented at the Annual Meeting of the American Gastroenterological Association held in San Diego, CA, USA, in May 2008. We greatly appreciate the help of our endoscopy room staff, Ms. Chieko Matsumoto, Ms Kinuko Maruyama, Ms Satoko Takebayashi, Ms Keiko Kikuchi and Ms Hitomi Tanaka.

Conflict of Interest Statement

None of the authors have any conflicts of interest related to this study.

Author information

Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Masafumi Nishino, Mitsushige Sugimoto, Chise Kodaira, Mihoko Yamade, Mutsuhiro Ikuma & Akira Hishida

  2. Department of Gastroenterology, Enshu General Hospital, Hamamatsu, Japan

    Naohito Shirai

  3. Department of Endoscopic & Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Tatsuo Tanaka

  4. First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Haruhiko Sugimura

  5. Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan

    Takahisa Furuta

Authors
  1. Masafumi Nishino
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  2. Mitsushige Sugimoto
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  3. Chise Kodaira
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  4. Mihoko Yamade
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  5. Naohito Shirai
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  6. Mutsuhiro Ikuma
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  7. Tatsuo Tanaka
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  8. Haruhiko Sugimura
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  9. Akira Hishida
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  10. Takahisa Furuta
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Corresponding author

Correspondence to Takahisa Furuta.

Additional information

Study highlights: we demonstrate for the first time that low dose aspirin induces gastric mucosal injury in the intragastric acidity-dependent manner in humans. We also show that aspirin induces dilatation of gastric subepithelial microvessels, which also depends on intragastric acidity. These endoscopic and histopathological changes can be prevented by concomitant treatment with rabeprazole, a proton-pump inhibitor.

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Nishino, M., Sugimoto, M., Kodaira, C. et al. Relationship Between Low-Dose Aspirin-Induced Gastric Mucosal Injury and Intragastric pH in Healthy Volunteers. Dig Dis Sci 55, 1627–1636 (2010). https://doi.org/10.1007/s10620-009-0920-3

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  • DOI: https://doi.org/10.1007/s10620-009-0920-3

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