Modification of pulmonary responses to endotoxemia in awake sheep by steroidal and nonsteroidal anti-inflammatory agents.

Abstract

The effects of intravenous infusions of Escherichia coli endotoxin on white blood cell counts, hemodynamics, gas exchange, body temperature, and lung lymph flow were studied in chronically instrumented unanesthetized sheep. Six sheep received endotoxin (0.5 micrograms/kg) in the presence and absence of methylprednisolone treatment. Six sheep received the same dose of endotoxin with and without meclofenamate and methylprednisolone infusion. Endotoxemia caused an early increase in pulmonary artery pressure from 15.5 +/- 1.3 (mean +/- SEM) to 52.7 +/- 2.1 cmH2O (p less than 0.05), an initial phase of high flow of protein-poor lung lymph, an elevation in core body temperature, severe leukopenia, and an early increase in the alveolar to arterial oxygen difference (AaPO2) from 7.4 +/- 2.5 mmHg to 35.9 +/- 2.5 mmHg (p less than 0.05). From 2 to 5 h after endotoxin infusion, lung lymph flow averaged 4.8 times that of the baseline measurement, although lymph protein concentration relative to plasma was not different from the baseline measurement. Peripheral leukopenia and significantly increased AaPO2 (28.8 +/- 4.5 mmHg) persisted at 2 to 5 h. Methylprednisolone attenuated the early pulmonary artery hypertension (43.0 +/- 3.4 cmH2O), but did not inhibit the initial febrile response, severe leukopenia, or the early increase in AaPO2 (29.2 +/- 1.6 mmHg) in response to endotoxemia. Methylprednisolone did prevent the late phase increase in lung lymph flow, significantly attenuated the late phase leukopenia and hypoxemia (AaPO2, 13.3 +/- 5.9 mmHg), and attenuated accumulation of granulocytes in peripheral lung tissue throughout the endotoxin reaction.(ABSTRACT TRUNCATED AT 250 WORDS)