Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals

Courtney M. Wheatley, Sarah E. Baker, Bryan J. Taylor, Manda L. Keller-Ross, Steven C. Chase, Alex R. Carlson, Robert J. Wentz, Eric M. Snyder, Bruce D. Johnson

Research output: Contribution to journalArticle

Abstract

Wheatley, Courtney M., Sarah E. Baker, Bryan J. Taylor, Manda L. Keller-Ross, Steven C. Chase, Alex R. Carlson, Robert J. Wentz, Eric M. Snyder, and Bruce D. Johnson. Influence of inhaled amiloride on lung fluid clearance in response to normobaric hypoxia in healthy individuals. High Alt Med Biol 18:343-354, 2017. Aim: To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5%) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. Results: Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5% ± 3.8% vs. -7.9% ± 5.2%, p < 0.05), (2) an increase in VC (53.6% ± 28.9% vs. 53.9% ± 52.3%, p < 0.05), (3) a small increase in DLCO (9.6% ± 29.3% vs. 9.9% ± 23.9%, p > 0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). Conclusion: Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged.

Original languageEnglish (US)
Pages (from-to)343-354
Number of pages12
JournalHigh Altitude Medicine and Biology
Volume18
Issue number4
DOIs
StatePublished - Dec 2017

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Amiloride
Lung
Extravascular Lung Water
Tomography
Epithelial Sodium Channels
Lung Volume Measurements
Hypoxia
Water-Electrolyte Balance
Extracellular Fluid
Carbon Monoxide
Blood Volume
Healthy Volunteers
Nitric Oxide
Thorax
Placebos
Oxygen

Keywords

  • chest computed tomography (CT)
  • diffusion capacity of the lungs for carbon monoxide and nitric oxide (DLCO/DLNO)
  • epithelial sodium channels (ENaC)

Cite this

Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals. / Wheatley, Courtney M.; Baker, Sarah E.; Taylor, Bryan J.; Keller-Ross, Manda L.; Chase, Steven C.; Carlson, Alex R.; Wentz, Robert J.; Snyder, Eric M.; Johnson, Bruce D.

In: High Altitude Medicine and Biology, Vol. 18, No. 4, 12.2017, p. 343-354.

Research output: Contribution to journalArticle

Wheatley, CM, Baker, SE, Taylor, BJ, Keller-Ross, ML, Chase, SC, Carlson, AR, Wentz, RJ, Snyder, EM & Johnson, BD 2017, 'Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals', High Altitude Medicine and Biology, vol. 18, no. 4, pp. 343-354. https://doi.org/10.1089/ham.2017.0032
Wheatley, Courtney M. ; Baker, Sarah E. ; Taylor, Bryan J. ; Keller-Ross, Manda L. ; Chase, Steven C. ; Carlson, Alex R. ; Wentz, Robert J. ; Snyder, Eric M. ; Johnson, Bruce D. / Influence of Inhaled Amiloride on Lung Fluid Clearance in Response to Normobaric Hypoxia in Healthy Individuals. In: High Altitude Medicine and Biology. 2017 ; Vol. 18, No. 4. pp. 343-354.
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abstract = "Wheatley, Courtney M., Sarah E. Baker, Bryan J. Taylor, Manda L. Keller-Ross, Steven C. Chase, Alex R. Carlson, Robert J. Wentz, Eric M. Snyder, and Bruce D. Johnson. Influence of inhaled amiloride on lung fluid clearance in response to normobaric hypoxia in healthy individuals. High Alt Med Biol 18:343-354, 2017. Aim: To investigate the role of epithelial sodium channels (ENaC) on lung fluid clearance in response to normobaric hypoxia, 20 healthy subjects were exposed to 15 hours of hypoxia (fraction of inspired oxygen [FiO2] = 12.5{\%}) on two randomized occasions: (1) inhaled amiloride (A) (1.5 mg/5 mL saline); and (2) inhaled saline placebo (P). Changes in lung fluid were assessed through chest computed tomography (CT) for lung tissue volume (TV), and the diffusion capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) for pulmonary capillary blood volume (VC). Extravascular lung water (EVLW) was derived as TV-VC and changes in the CT attenuation distribution histograms were reviewed. Results: Normobaric hypoxia caused (1) a reduction in EVLW (change from baseline for A vs. P, -8.5{\%} ± 3.8{\%} vs. -7.9{\%} ± 5.2{\%}, p < 0.05), (2) an increase in VC (53.6{\%} ± 28.9{\%} vs. 53.9{\%} ± 52.3{\%}, p < 0.05), (3) a small increase in DLCO (9.6{\%} ± 29.3{\%} vs. 9.9{\%} ± 23.9{\%}, p > 0.05), and (4) CT attenuation distribution became more negative, leftward skewed, and kurtotic (p < 0.05). Conclusion: Acute normobaric hypoxia caused a reduction in lung fluid that was unaffected by ENaC inhibition through inhaled amiloride. Although possible amiloride-sensitive ENaC may not be necessary to maintain lung fluid balance in response to hypoxia, it is more probable that normobaric hypoxia promotes lung fluid clearance rather than accumulation for the majority of healthy individuals. The observed reduction in interstitial lung fluid means alveolar fluid clearance may not have been challenged.",
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AU - Keller-Ross, Manda L.

AU - Chase, Steven C.

AU - Carlson, Alex R.

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