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Antioxidants Increase the Ventilatory Response to Hyperoxic Hypercapnia

Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece

Correspondence and requests for reprints should be addressed to Spyros G. Zakynthinos, M.D., Medical School of Athens University, Department of Critical Care and Pulmonary Services, Evangelismos Hospital, 45-47 Ipsilandou St., GR 106 75 Athens, Greece. E-mail: szakynthinos{at}yahoo.com

Rationale: The mechanisms by which chemoreceptors process carbon dioxide stimuli are poorly understood. Recent in vitro studies suggest a role of reactive oxygen species in central carbon dioxide chemoreception.

Objectives: We tested the hypothesis that antioxidant treatment modulates the ventilatory response to carbon dioxide in healthy humans, either during unloaded breathing or after strenuous resistive breathing.

Methods: In the first experiment of this randomized, double-blind, placebo-controlled study, 14 healthy males completed hyperoxic carbon dioxide rebreathing, received either antioxidants (vitamins E, A, and C for 2 mo, allopurinol for 15 d, and N-acetylcysteine for 3 d) (n = 7) or placebo (n = 7), and repeated rebreathing 3 mo later. In the second experiment, 18 healthy males completed a series of rebreathing tests before and after strenuous resistive breathing. Subjects repeated the same protocol 3 mo later, after they had received antioxidants (n = 9) or placebo (n = 9).

Main Results: After antioxidants, the sensitivity of the ventilatory (minute ventilation) response to carbon dioxide increased (mean [± SEM], 3.2 ± 0.5 vs. 1.7 ± 0.4 L/min/mm Hg; p < 0.001). Antioxidants also increased the sensitivity to carbon dioxide before and at 5, 30, and 120 min after resistive breathing (p = 0.01). This effect was entirely due to increased tidal volume. Antioxidants did not influence the breathing pattern during resting breathing or the rapid shallow breathing response to carbon dioxide at 5 min after resistive breathing.

Conclusions: Antioxidants, by augmenting the tidal volume, increase the sensitivity of the ventilatory response to carbon dioxide, either during unloaded breathing or after resistive breathing.

Key Words: central chemoreception • control of breathing • reactive oxygen species

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Recent studies have provided clues to the fundamental role of reduction–oxidation (redox) reactions and reactive oxygen species in central carbon dioxide chemoreception. What This Study Adds to the Field Antioxidants augment the tidal volume, thereby increasing the sensitivity of the ventilatory response to carbon dioxide in healthy humans during unloaded breathing and after resistive breathing.

 

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