Effect of endotoxin on ventilation and breath variability - Role of cyclooxygenase pathway

To evaluate the effects of endotoxemia on respiratory controller function, 12 subjects were randomized to receive endotoxin or saline; six also receiv ed ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Adminis tration of endotoxin produced fever, increased respiratory frequency, decre ased inspiratory time, and widened alveolar-arterial oxygen tension gradien t (all p less than or equal to 0.001); these responses were blocked by ibup rofen. Independent of ibuprofen, endotoxin produced dyspnea, and it increas ed fractional inspiratory time, minute ventilation, and mean inspiratory fl ow (all p less than or equal to 0.025). Endotoxin altered the autocorrelati ve behavior of respiratory frequency by increasing its autocorrelation coef ficient at a lag of one breath, the number of breath lags with significant serial correlations and its correlated fraction (all p < 0.05); these respo nses were blocked by ibuprofen. Changes in correlated behavior of respirato ry frequency were related to changes in arterial carbon dioxide tension (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspirat ory time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In conclusion, endotoxin produced increases in respiratory motor output and d yspnea independent of fever and symptoms, and it curtailed the freedom to v ary respiratory timing-a response that appears to be mediated by the cycloo xygenase pathway.