The Therapeutic Effect of Bronchoalveolar Lavage with KL₄-Surfactant in Animal Models of Meconium Aspiration Syndrome. † 1578

Animal models of Meconium Aspiration Syndrome (MAS) were established in adult rabbits and newborn rhesus monkeys. Rabbits were given a slurry of human meconium intratracheally. A dose of 187.5 mg/kg resulted in a drop in PaO₂ from approximately 500 to <100 mmHg on FiO₂ = 1.0. Untreated control animals remained atelectatic, had greatly decreased lung compliance, and developed severe inflammation 3-5 hours after the meconium injury. Twelve meconium-injured rabbits were treated with 2-4 bronchoalveolar lavages with dilute KL₄-Surfactant, a synthetic pulmonary surfactant containing an SP-B-like peptide. These rabbits showed a rapid and sustained recovery of PaO₂ to approx. 400 mmHg within minutes, a return towards normal compliance, and greatly diminished inflammation. Five additional injured rabbits were lavaged with saline; although meconium was removed from the lungs to the same extent as with lavage with KL₄-Surfactant, these animals showed no rise in PaO₂, no increase in compliance, and no diminution of inflammation in their lungs. Ten full-term Cesarean-delivered rhesus monkeys were given an intratracheal instillation of slurried human meconium prior to the first breath (mean quantity instilled = 553.1 mg/kg). All developed rapid onset of ventilatory failure, requiring FiO₂ of 0.8- 1.0 with a/A ratios <0.2 and chest radiographs showing generalized opacity. Treatment of these monkeys 1-5 hours after birth and meconium injury with bronchoalveolar lavage with dilute KL₄-Surfactant produced clearing of the chest radiographs and a rapid improvement in gas exchange with a/A ratios rising into the normal range where they remained through the 20-hour period of study. The monkeys were breathing room air approx. 11 hours after treatment. Control animals not receiving lavage with KL₄-Surfactant failed to improve a/A ratios, maintained opacity in chest radiographs, and showed severe atelectasis and inflammation at necropsy. These studies indicate that bronchoalveolar lavage with dilute KL₄-Surfactant is successful in improving pulmonary function in two animal models of MAS; clinical trials in human infants with meconium aspiration appear warranted.

(Funded, in part, by the R. W. Johnson Pharmaceutical Research Institute.)