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Methylprednisolone prevention of increased lung vascular permeability following endotoxemia in sheep
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 mug/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 H(2)O 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.
Insights
Methylprednisolone prevents endotoxin-induced lung vascular permeability increases in sheep when given before or early in endotoxemia. However, it does not reverse this lung injury once it has occurred.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Critical Care Medicine
Background:
- Endotoxemia, often caused by Gram-negative bacteria, leads to significant pulmonary complications.
- Increased lung vascular permeability is a hallmark of endotoxemia, contributing to lung injury.
- The role of corticosteroids like methylprednisolone in mitigating these responses requires further elucidation.
Purpose of the Study:
- To investigate the effect of methylprednisolone on the pulmonary vascular response to endotoxemia in an ovine model.
- To determine if methylprednisolone can prevent or reverse endotoxin-induced increases in lung vascular permeability.
Main Methods:
- Chronically instrumented, unanesthetized sheep were used to study responses to endotoxin infusion.
- Pulmonary artery pressure, left atrial pressure, lung lymph flow (Qlym), and lymph/plasma protein concentration (L/P) were measured.
- Methylprednisolone was administered before or during endotoxin challenge.
Main Results:
- Endotoxin infusion caused initial pulmonary hypertension and a subsequent increase in lung vascular permeability (elevated Qlym and L/P).
- Pre-treatment with methylprednisolone attenuated the initial pulmonary hypertension and prevented the late-phase increase in lung vascular permeability.
- Methylprednisolone administered during the hypertensive response also prevented increased permeability, but was ineffective once permeability was already elevated.
Conclusions:
- Large doses of methylprednisolone administered before or shortly after endotoxemia can prevent endotoxin-induced increases in lung vascular permeability.
- Methylprednisolone does not reverse established lung vascular permeability increases caused by endotoxin.
- These findings suggest a prophylactic or early intervention role for methylprednisolone in endotoxemia-related lung injury.
