The effects of a prostaglandin synthetase inhibitor, ibuprofen, on the cardiopulmonary response to endotoxin in sheep.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D001810:Blood Volume / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology*; D007958:Leukocyte Count; D008196:Lymph / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects
D001798:Blood Proteins; D004731:Endotoxins; D007052:Ibuprofen