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Effect of Amiloride on Experimental Acid-Induced Heartburn in Non-erosive Reflux Disease

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Abstract

Background

Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion.

Methods

In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent.

Results

14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05).

Conclusions

Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.

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Acknowledgments

This research was conducted with financial support from the Investigator Sponsored Study Program of AstraZeneca. Dr. Hansen of Astra Zeneca provided expertise in the design of the trial, interpretation of the findings and in the development of this manuscript.

Conflict of interest

None.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Center for Esophageal Diseases and Swallowing Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    William J. Bulsiewicz, Nicholas J. Shaheen, Amy Pruitt & Roy C. Orlando

  2. AstraZeneca R&D, Mölndal, Sweden

    Mark B. Hansen

Authors
  1. William J. Bulsiewicz
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  2. Nicholas J. Shaheen
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  3. Mark B. Hansen
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  4. Amy Pruitt
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  5. Roy C. Orlando
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Corresponding author

Correspondence to William J. Bulsiewicz.

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Bulsiewicz, W.J., Shaheen, N.J., Hansen, M.B. et al. Effect of Amiloride on Experimental Acid-Induced Heartburn in Non-erosive Reflux Disease. Dig Dis Sci 58, 1955–1959 (2013). https://doi.org/10.1007/s10620-013-2586-0

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  • DOI: https://doi.org/10.1007/s10620-013-2586-0

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