ARTIFICIAL SURFACTANT ATTENUATES HYPEROXIC LUNG INJURY IN PRIMATES .1. PHYSIOLOGY AND BIOCHEMISTRY

Prolonged exposure to O-2 causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O-2 exposure in primates. Sixteen healthy male baboons (10-15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O-2 (n = 6) or 100% O-2 plus aerosolized artificial surfactant (Exosurf; n = 5). A third group of animals (n = 5) was ventilated with an inspired fraction of O-2 of 0.21 to control for the effects of sedation and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution (V-A/Q) was measured daily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH(2)O and was intermittently raised to 10 cmH(2)O for 30 min to obtain additional measurements of V-A/Q After the experiments, lungs were obtained for biochemical and histological assessment of injury. O-2 exposures altered hemodynamics, progressively worsened V-A/Q, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturated phosphatidylcholine in lavage fluid and improved intrapulmonary shunt, arterial PO2, and lung edema. Surfactant also enhanced the shunt-reducing effect of positive end-expiratory pressure. We conclude that an aerosolized protein-free surfactant decreased the progression of pulmonary O-2 toxicity in baboons.