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J Appl Physiol 94: 141-154, 2003. First published September 6, 2002; doi:10.1152/japplphysiol.00594.2002
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Vol. 94, Issue 1, 141-154, January 2003

Hypoxic and hypercapnic drives to breathe generate equivalent levels of air hunger in humans

S. H. Moosavi1,2, E. Golestanian2,3, A. P. Binks1,2, R. W. Lansing1,4, R. Brown2,5, and R. B. Banzett1,2,5

1 Physiology Program, Harvard School of Public Health, 3 Pulmonary/Critical Care Medicine, Brigham and Women's Hospital, and 5 Department of Medicine, Harvard Medical School, Boston 02115; and 2 Pulmonary Department, Veterans Affairs Boston Healthcare System, West Roxbury Campus, Massachusetts 02132; and 4 Department of Psychology, University of Arizona, Tucson, Arizona 85721

Anecdotal observations suggest that hypoxia does not elicit dyspnea. An opposing view is that any stimulus to medullary respiratory centers generates dyspnea via "corollary discharge" to higher centers; absence of dyspnea during low inspired PO2 may result from increased ventilation and hypocapnia. We hypothesized that, with fixed ventilation, hypoxia and hypercapnia generate equal dyspnea when matched by ventilatory drive. Steady-state levels of hypoxic normocapnia (end-tidal PO2 = 60-40 Torr) and hypercapnic hyperoxia (end-tidal PCO2 = 40-50 Torr) were induced in naive subjects when they were free breathing and during fixed mechanical ventilation. In a separate experiment, normocapnic hypoxia and normoxic hypercapnia, "matched" by ventilation in free-breathing trials, were presented to experienced subjects breathing with constrained rate and tidal volume. "Air hunger" was rated every 30 s on a visual analog scale. Air hunger-PETO2 curves rose sharply at PETO2 <50 Torr. Air hunger was not different between matched stimuli (P > 0.05). Hypercapnia had unpleasant nonrespiratory effects but was otherwise perceptually indistinguishable from hypoxia. We conclude that hypoxia and hypercapnia have equal potency for air hunger when matched by ventilatory drive. Air hunger may, therefore, arise via brain stem respiratory drive.

visual analog scale; perception; adverse electrocardiogram effects; steady state; shortness of breath; breathlessness


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