Dexamethasone and indomethacin modify endotoxin-induced respiratory failure in pigs.
We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0-2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2-4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004731:Endotoxins; D004926:Escherichia coli; D006321:Heart / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000503:physiopathology; D011652:Pulmonary Circulation; D012128:Respiratory Distress Syndrome / Q000503:physiopathology; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D013552:Swine; D013553:Swine Diseases / Q000503:physiopathology*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D003907:Dexamethasone; D007213:Indomethacin