A phospholipase inhibitor modifies the pulmonary damage associated with peritonitis in rabbits

Peritonitis has been produced in rabbits by the spreading of 5 ml of caecal contents throughout the peritoneal cavity. After sacrifice at 5 h, electron microscopy revealed a increase of 600% in PMN and 1200% in lymphocytes in the pulmonary capillaries of the test animals when compared to the sham operated group. The pulmonary capillaries in the test group showed a 27% reduction in their luminal area, which was associated with a 73% reduction in their patency due to occlusion by WBC and cell debris. In addition there was endothelial and epithelial disruption with basement membrane exposure. The PMN were degranulated and adherent to the pulmonary endothelium. Pretreatment with the phospholipase inhibitor, mepacrine, significantly attenuated these responses, so that there was only an increase of 200% in PMN and 450% in lymphocytes in the lungs with no evidence of degranulation or adhesion to the pulmonary endothelium. Furthermore there was no change in capillary luminal area when compared to the sham operated group. In addition there was only slight damage to the endothelium and epithelium with no exposure of the basement membrane. Peripheral WBC in both the test and mepacrine groups showed a similar 62% and 75% reduction after 5 h when compared to baseline values. The sham group did not show this change. These results suggest that phospholipase inhibition plays an important role in attenuating the pulmonary response to faecal peritonitis and may be of potential benefit in treating clinical septicaemia.