of Work: Administration of endotoxin to humans allows a unique way to evaluate the early inflammatory reactions that occur during infection. Characterizing these responses and the mechanisms that control them is important because these inflammatory responses contribute to the development of septic shock and organ failure. Few data are available describing the effects on respiratory drive and frequency of acute inflammation induced by endotoxin. This information may have implications for the development of respiratory failure during sepsis. We have previously shown that intravenous (IV) endotoxin leads to a loss of heart rate variability and an increase in heart rate regularity, as reflected by a decrease in approximate entropy and power spectra. Similar analyses of respiratory frequency will be performed in subjects given either IV endotoxin alone or endotoxin with ibuprofen, using respiratory inductive plethysmography to monitor breathing patterns, respiratory drive, frequency, and muscle strength. In subjects given ibuprofen, symptoms and fever do not develop but similar hemodynamic responses to endotoxin remain. This information will link data relating to hemodynamic and respiratory responses to endotoxin in humans. In a parallel study, we will evaluate the initial human responses to localized pulmonary inflammation after endotoxin is instilled into a segmental bronchus. A control group will be studied in a similar fashion to control for the effects of bronchoscopy on ventilatory response.
