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 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 < or = 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 < or = 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 timing-a response that appears to be mediated by the cyclooxygenase pathway.
Preas
H L
HL
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Jubran
A
A
Vandivier
R W
RW
Reda
D
D
Godin
P J
PJ
Banks
S M
SM
Tobin
M J
MJ
Suffredini
A F
AF
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000097:blood; D004417:Dyspnea / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D019446:Endotoxemia / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D004731:Endotoxins / Q000009:adverse effects*; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007052:Ibuprofen / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000276:immunology*; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000276:immunology*; D012132:Respiratory Muscles / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D016037:Single-Blind Method
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004731:Endotoxins; D002245:Carbon Dioxide; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen