Ibuprofen and Diphenhydramine Reduce the Lung Lesion of Endotoxemia in Sheep

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Abstract
Endotoxin (0.75 μg/kg) was administered to unanesthetized sheep with and without premedication with ibuprofen, a cyclooxygenase inhibitor, and diphenhydramine, an antihistamine. The effect of the endotoxin on cardiopulmonary and lung lymph data and their alteration by the drug regimen was assessed. The cardiopulmonary responses to endotoxin can be defined into two phases. In phase I there is an elevation in protein-poor lung lymph flow, in pulmonary artery pressure (PA), and in hematocrit, and a reduction in cardiac index and leukocyte count. Phase II occurs late and shows much the same changes as phase I except that the PA is not as high and the lymph protein is increased. The drug combination (ibuprofen and diphenhydramine) virtually eliminates the phase I reponse. The phase II changes in lymph flow and protein content are affected by diphenhydramine but not ibuprofen. The cardiovascular changes which occur during this period are not affected by either agent.