Am. J. Respir. Crit. Care Med., Volume 164, Number 4, August 2001, 620-626

Effect of Endotoxin on Ventilation and Breath Variability
Role of Cyclooxygenase Pathway

HUGH L. PREAS II, AMAL JUBRAN, R. WILLIAM VANDIVIER, DEBRA REDA, PAUL J. GODIN, STEVEN M. BANKS, MARTIN J. TOBIN, and ANTHONY F. SUFFREDINI

Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland; and The Division of Pulmonary and Critical Care Medicine, Edward Hines Jr., Veterans Affairs Hospital and Loyola University of Chicago Stritch School of Medicine, Hines, Illinois

To evaluate the effects of endotoxemia on respiratory controller function, 12 subjects were randomized to receive endotoxin or saline; six also received ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Administration of endotoxin produced fever, increased respiratory frequency, decreased inspiratory time, and widened alveolar-arterial oxygen tension gradient (all p  0.001); these responses were blocked by ibuprofen. Independent of ibuprofen, endotoxin produced dyspnea, and it increased fractional inspiratory time, minute ventilation, and mean inspiratory flow (all p  0.025). Endotoxin altered the autocorrelative behavior of respiratory frequency by increasing its autocorrelation coefficient at a lag of one breath, the number of breath lags with significant serial correlations, and its correlated fraction (all p < 0.05); these responses were blocked by ibuprofen. Changes in correlated behavior of respiratory frequency were related to changes in arterial carbon dioxide tension (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspiratory time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In conclusion, endotoxin produced increases in respiratory motor output and dyspnea independent of fever and symptoms, and it curtailed the freedom to vary respiratory timinga response that appears to be mediated by the cyclooxygenase pathway.

Keywords: endotoxemia; respiratory center; Fourier analysis; sepsis; respiratory muscles

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