Correlation of Changes in Pulmonary Surfactant Phospholipids with Compliance in Bleomycin-Induced Pulmonary Fibrosis in the Rat

Abstract
Qualitative and quantitative analysis was performed on phospholipids isolated from bronchoalveolar lavage fluid during the development of pulmonary fibrosis in the rat. A single transtracheal injection of 2.0 units of bleomycin was administered to rats to induce lung injury. Animals were killed at 0, 3, 7, 14, 30, and 120 days after bleomycin treatment. Total lipid phosphorus in BAL from animals given bleomycin increased from 1.6 .mu.mol/lung in normal animals to 3.2 .mu.mol/lung at 14 and 30 days. The increase in phospholipids was primarily in phosphatidylcholine with minor increases in phosphatidylinisitol and phosphatidylethanolamine. These quantitative changes were accompanied by qualitative changes that included an increase in the percentage of total phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylinositol. In contrast, the percentage of phosphatidylglycerol was significantly reduced. Plasma phospholipid analysis indicated that these alterations were not due to plasma contamination. The functional significance of the phospholipid changes was assessed by comparing air- and saline-filled compliance measurements at similar times after bleomycin. Abnormal compliance measurements were observed at 3, 7, and 14 days after bleomycin. At 3 and 7 days the predominant compliance defect was at the air-liquid interface; however, at 14 days, when phospholipids were significantly elevated, the defect was primarily due to tissue components. We conclude that changes in surfactant composition and concentration occur during the development of bleomycin-induced pulmonary fibrosis in the rat and that these changes coincide with altered lung compliance.