EVALUATION OF POTENTIALLY INJURIOUS EFFECTS OF EXOGENOUS SURFACTANT LYSOPHOSPHOLIPIDS ON THE ALVEOLAR EPITHELIUM AND PULMONARY MECHANICS

Although lysophospholipids are normally found in the lung and their pr esence is connected to the metabolic pathway of surfactant phospholipi ds, several studies have reported that their intratracheal instillatio n is able to induce severe alveolar epithelial injury. Since lysophosp holipids are normally present in exogenous surfactants as a consequenc e of the nonenzymatic hydrolysis of parent phospholipids during their production and shelf-life, the aim of this study was to test the poten tial toxicity of surfactant lysophospholipids in artificially ventilat ed newborn rabbits in comparison with that of pure lysophosphatidylcho line (Lyse-PC) suspensions. In premature (surfactant-deficient) animal s, a commercially available Curosurf batch (0.56 mg Lyso-PC/ml) improv ed lung-thorax compliance and reduced lactate dehydrogenase (LDH), tot al protein and hemoglobin contents in bronchoalveolar lavage (BAL) flu id. The same batch submitted to thermal stress in order to increase th e Lyse-PC content (10.2 mg Lyso-PC/ml) failed to improve lung mechanic s but did not induce any significant change in biochemical markers in BAL fluid. When suspended in saline, pure Lyse-PC had a dramatic and d ose-dependent tissue-damaging effect with increased LDH, hemoglobin an d protein contents in BAL and a fall in the lung-thorax compliance, in both immature and mature (near-term) animals. The lack of toxicity of Lyso-PC in Curosurf might be explained by an interaction with surfact ant phospholipids.