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This study compares qualitative and quantitative differences between the cardiopulmonary responses to Salmonella typhimurium and Escherichia coli 055:B5 endotoxins (Difco) in the same sheep model. Lipopolysaccharides, 0.75 micrograms/kg, were infused into chronically instrumented sheep over 30 min. Cardiopulmonary and pulmonary lymph flux data were collected for 2 h prior to and 6 h following this. One week later the sequence was repeated with another endotoxin. The administration of the two endotoxins was varied: some received S. typhimurium first; others received E. coli. A total of 13 animals were studied; 8 had intact pulmonary lymphatic catheters. Following each injection of endotoxin these animals showed a typical response of early high pressure-mediated increase in pulmonary lymph flow and later lymph flow elevation associated with a very mild increase in microvascular pressure and lymph with normal protein levels. These changes were associated with hemoconcentration, lowered arterial oxygen partial pressure, cardiac index, and blood neutrophil count. It is concluded that Difco S. typhimurium and E. coli endotoxins are similar in their mechanism of action and potency and can be studied in the same animal.

Prostaglandins released during inflammatory reactions cause increases in microvascular hydrostatic pressure, a primary cause of edema. Ibuprofen, a nonsteroidal, anti-inflammatory agent that reduces prostaglandin synthesis via inhibition of cyclooxygenase, was used to investigate the possible role of prostaglandins in the cardiopulmonary responses during sepsis. Sheep, surgically prepared for cardiopulmonary studies and collection of lung lymph, were given 0.75 micrograms/kg per 30 min of E. coli endotoxin iv. Ibuprofen (14 mg/kg) was given 15 min before and 1 h 45 min after the administration of endotoxin. We had previously noted a triphasic character to the hypovolemia encountered in endotoxin sepsis. The initial phase occurs during the first hour after endotoxin administration; it is characterized by decreases in PaO2, neutrophil count, and lymph-to-plasma (L/P) protein concentration ratios and by increases in mean arterial pressure, body temperature, hematocrit, lymph flow, and total plasma protein concentration. In the second phase these variables return toward their baseline values. In Phase 3 the same changes are observed an in Phase 1 except for a decrease in total plasma protein concentration and an increase in L/P ratios. Ibuprofen administration results in a statistically significant reduction in magnitude of Phase 1 changes, without notable effect on Phase 2 or Phase 3 values. These observations support the hypothesis that prostaglandins released during inflammatory reactions contribute to the extravascular fluid movement. Ibuprofen appears to lessen the severity of microvascular hydrostatic pressure-induced edema and the hypovolemia that occurs in the early stages of endotoxin.