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. 1981 Apr;67(4):1103–1110. doi: 10.1172/JCI110123

Methylprednisolone Prevention of Increased Lung Vascular Permeability following Endotoxemia in Sheep

Kenneth L Brigham 1, Ronald E Bowers 1, Charles R McKeen 1
PMCID: PMC370670  PMID: 7009652

Abstract

To see whether methylprednisolone would affect the pulmonary vascular response to endotoxemia, we studied responses to endotoxemia in the presence and absence of methylprednisolone in the same chronically instrumented, unanesthetized sheep. Infusion of Escherichia coli endotoxin (0.70-1.33 μg/kg) caused an initial period of marked pulmonary hypertension followed several hours later by a long period of increased vascular permeability when pulmonary vascular pressures were near base line (base-line pulmonary artery pressure (PPa) = 21±1 cm H2O SE, left atrial pressure (Pla) = 1±3; experimental PPa = 20±3, Pla = 3±4; P = NS), lung lymph flow (˙Qlym) was high (base-line ˙Qlym = 7.2±0.2 ml/h; experimental ˙Qlym = 23.2±1.0; P < 0.05) and lymph/plasma protein concentration (L/P) was high (base-line L/P = 0.65±0.04; experimental L/P = 0.79±0.05; P < 0.05). When methylprednisolone (1.0 g + 0.5 g/h i.v.) was begun 30 min before the same dose of endotoxin was infused, the initial pulmonary hypertension was less and the late phase increase in lung vascular permeability was prevented (experimental PPa = 24±1, Pla = 1±1, ˙Qlym = 10.0±0.4; L/P = 0.56±0.03). ˙Qlym and L/P were significantly (P < 0.05) lower than with endotoxin alone. Methylprednisolone began during the initial pulmonary hypertensive response to endotoxin also prevented the late phase increase in lung vascular permeability, but the drug had no effect once vascular permeability was increased. We conclude that large doses of methylprednisolone given before or soon after endotoxemia prevent the increase in lung vascular permeability that endotoxin causes, but do not reverse the abnormality once it occurs.

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Selected References

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