Protocol (92-CC-0141) is evaluating the acute effects of endotoxin administration on human cardiopulmonary function. Endotoxin administration to humans provides an opportunity t evaluate the earliest inflammatory responses that are activated after exposure to an important and common bacterial component. Defining these pathways and their interactions may allow a better understanding of the factors that can be controlled or altered during critical illness. The current protocol will extend previous observations of endotoxin on heart lung function in three separate studies. 1) Using bronchoalveolar lavage, the effects of direct instillation of endotoxin into a lobe of the lung will be used to assess local pulmonary inflammatory responses. 2) Using flow transducers, esophageal balloons and respiratory inductive plethysmography, respiratory muscle strength will be evaluated after endotoxin. 30 Systemic hemodynamics and inflammatory responses will be evaluated following two doses of endotoxin given with 4-6 hours of each other in order to evaluate mechanisms of endotoxin tolerance. The goal of these studies is to learn more about mechanisms that control acute inflammatory responses in a model relevant to human septic shock. Knowledge of these control mechanisms will assist in the development of new therapies for septic shock.
