The role of high dose corticosteroids (HDC) in pulmonary capillary-alveolar membrane integrity.

Disturbed microvascular integrity is an initial event in the development of respiratory insufficiency following trauma and shock. Increased permeability in the pulmonary microvessels has been demonstrated in both experimental animals and in man. High dose corticosteroids have been used to prevent the development of the permeability lesion and to reduce it once it has occurred. Data from experimental animals are indicative of a positive effect of HDC and in patients with adult respiratory distress syndrome leakage of macromolecules over the capillary alveolar membrane was reduced significantly. Using the lung lymph fistula preparation in sheep we have demonstrated that the pulmonary microvascular sieving capacity was reduced (as indicated by a reduced osmotic reflection coefficient) following the operative trauma and manipulation of lungs necessary for cannulation of the lymphatics. We studied the effects of HDC (methyl-prednisolone 30 mg/kg) given preoperatively in 7 operated sheep and compared to 3 nonoperated controls. Permeability surface area product (PS) and osmotic reflection coefficient (sigma) for total protein were calculated by iterative curve fitting using the non-linear flux equation and data were compared to sigma achieved at maximal lymph flow following increased left atrial pressure. After surgery there were no differences between the two groups in baseline observations. In the experimental group lymph to plasma ratio for total protein (L/P) at maximal lymph flow was 0.46 +/- 0.09 corresponding to a sigma of 0.54. Maximal lymph flow was attained at microvascular pressure (Pmv) 38 +/- 2 mmHg. Calculated sigma was 0.61 +/- 0.03 and PS 0.09 +/- 0.01. Corresponding values in the control group were 0.69 +/- 0.003 and 0.1 +/- 0.0003 respectively. L/P at maximal lymph flow was 0.39 +/- 0.04 at Pmv = 35 +/- 6 mmHg in the control group. In this experiment HDC did not prevent the increase in pulmonary microvascular permeability as demonstrated after operative trauma by a decrease in the osmotic reflection coefficient for total protein. Data from patients indicate however, that HDC may have a beneficial effect on the integrity of the alveolar capillary membrane. Further studies are needed to elucidate these problems.