Alterations in Lung Surfactant Disaturated Phosphatidylcholine, SP-A, and SP-B in Meconium Injured Rats Lavaged with Perfluorochemical (PFC) or KL4 Surfactant † 1600

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Meconium aspiration remains a common cause of respiratory distress from lung injury and surfactant inhibition. Meconium debris in the lung can be removed by lavage with KL4 surfactant, a mixture of phospholipids (PL) and synthetic peptide (Revak, Pediatr Res, 41;264A,1997), or with PFC which are used to maintain gas exchange. In these models, however the status of lung surfactant composition remains unclear. In a rat model of meconium injury, we have evaluated if lung lavage alters the surfactant disaturated phosphatidylcholine (DSPC) and proteins SP-A and SP-B in spontaneously breathing animals. Adult rats were intubated and given 0.3 ml meconium (13.5 mg dry wt) or saline (NS, n=3) endotracheally. Ten minutes later, meconium instilled lungs (Mec) were lavaged (x 3) with 6 ml/kg aliquots of saline (NSL, n=5) or PFC (PFCL, n=5). One group of Mec rats was lavaged twice with saline suspension of KL4 at 2.5 mg/ml, and once at 10 mg/ml (KL4L, n=5); another group was lavaged twice with saline, followed by once with KL4 at 10mg/ml, in order to replenish surfactant washed out with saline lavages (SKL4L, n=5). Animals were extubated after recovering from anesthesia (1-2 hours) to spontaneously breathe room air for 18 hours, a period previously shown to correlate with maximal lung injury in this model. Thereafter, bronchoalveolar lavage fluid (BAL) was obtained on excised lungs and seperated into large(Lag) and small surfactant aggregates. BAL fractions and lung tissue were analyzed for DSPC content and Lag for SP-A and SP-B. DSPC levels (μg lipid phosphorus/lung) were similar in Lag of Mec (12.5±2.1, mean±SE, n=4) and NS animals (9.5±0.2, p=0.06). They were slightly elevated in PFCL group (14.0±0.5, p>0.05, vs Mec) and significantly elevated in KL4L (87±19, p<0.001, vs Mec) and NSKL4L groups (48±8, p<0.001, vs Mec). DSPC levels in the lung tissue were similar in Mec(138±14) and NS animals 189±17, p=0.06). The lungs of KL4L(330±85, p<0.02) and NSKL4L animals (256±42, p<0.05) also showed higher levels of DSPC compared to Mec animals (138±20). In Western blots of Lag, both SP-A and SP-B were decreased in NSL group compared with NS or Mec animals, suggesting that saline lavage depleted SP. Both proteins were elevated in KL4L compared to NSL animals. We speculate that KL4 lavage may lead to metabolic changes that result in increased retention of PL in lung tissue, and may affect SP metabolism to prevent their depletion in lung surfactant. KL4 was a gift of Acute Therapeutics, Inc, Doylestown, Pa.