Phospholipase A₂-induced lung edema and its mechanism in isolated perfused guinea pig lung

Abstract

Lung injury induced by phospholipase A₂ (PLA₂, 0.046 IU/ml perfusate) was studied in a continuous weighing system of isolated perfused guinea pig lungs. The results revealed that lung weight increased progressively during the 30-min perfusion of PLA₂. No change of pulmonary arterial pressure was observed in the same period. Albumin permeability-surface area product, lung index, lung water content, exudate from pleura, and angiotensin-converting-enzyme activity increased significantly at the end of 30 min PLA₂ perfusion.p-Bromophenacyl bromide, a PLA₂ inhibitor, may block the above changes nearly completely. The effects of inhibitors of cyclooxygenase (indomethacin, IM), lipoxygenase (diethylcarbamaxine, DE), and platelet-activating factor (SRI 63-441) on PLA₂-induced lung injury were also studied. We found: (1) PLA₂ may induce high permeability lung edema. The role of endothelial injury in the permeability change remains to be further investigated. (2) DE ameliorated lung injury significantly within 10 min of PLA₂ treatment but showed no effect after 15 min. IM ameliorated lung injury during the whole experimental period. SRI 63-441 had no effect. It is suggested that PLA₂ may damage lung by inducing products of cyclooxy genase and lipoxygenase besides its direct effect.