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 presence is connected to the metabolic pathway of surfactant phospholipids, several studies have reported that their intratracheal instillation is able to induce severe alveolar epithelial injury. Since lysophospholipids are normally present in exogenous surfactants as a consequence of the nonenzymatic hydrolysis of parent phospholipids during their production and shelf-life, the aim of this study was to test the potential toxicity of surfactant lysophospholipids in artificially ventilated newborn rabbits in comparison with that of pure lysophosphatidylcholine (Lyso-PC) suspensions. In premature (surfactant-deficient) animals, a commercially available Curosurf batch (0.56 mg Lyso-PC/ml) improved lung-thorax compliance and reduced lactate dehydrogenase (LDH), total protein and hemoglobin contents in bronchoalveolar lavage (BAL) fluid. The same batch submitted to thermal stress in order to increase the Lyso-PC content (10.2 mg Lyso-PC/ml) failed to improve lung mechanics but did not induce any significant change in biochemical markers in BAL fluid. When suspended in saline, pure Lyso-PC had a dramatic and dose-dependent tissue-damaging effect with increased LDH, hemoglobin and protein contents in BAL and a fall in the lungthorax 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 surfactant phospholipids.
Fornasier
M
M
Chiesi Farmaceutici, Parma, Italia.
Puccini
P
P
Razzetti
R
R
Acerbi
D
D
Bongrani
S
S
Ventura
P
P
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007442:Intubation, Intratracheal; D008168:Lung / Q000737:chemistry / Q000503:physiopathology; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D015656:Respiratory Mechanics / Q000187:drug effects*; D015996:Survival Rate
D008244:Lysophosphatidylcholines