Prevention of rabbit acute lung injury by surfactant, inhaled nitric oxide, and pressure support ventilation

Improvement of pulmonary perfusion and blood oxygenation and prevention of acute lung injury (ALI) may rely on ventilation strategy. We hypothesized t hat application of a combined surfactant, inhaled nitric oxide (iNO), and p ressure support ventilation (PSV) should more effectively protect the lungs from injury. Anesthetized and intubated adult rabbits weighing 2.8 +/- 0.3 kg were allowed to breathe room air while receiving oleic acid intravenous ly (60 mu l/kg). Within 90 min this caused a reduction of Pa-O2 from 94 +/- 7 to 48 +/- 3 mm Hg and dynamic lung compliance (Cdyn) from 1.59 +/- 0.22 to 0.85 +/- 0.10 ml/cm H2O/kg (both p < 0.01), and increase of intrapulmona ry shunting ((Q) over dot s/(Q) over dot T) from 9.4 +/- 1.2 to 27 +/- 5% ( p < 0.05). PSV was subsequently applied with 3 cm H2O of continuous positiv e airway pressure and FIO2 of 0.3, and the animals were randomly allocated to four groups, receiving: (1) PSV only (Control, n = 10); (2) iNO at 20 pp m (NO, n = 9); (3) surfactant phospholipids at 100 mg/kg (Surf, n = 8); and (4) surfactant at 100 mg/kg and iNO at 20 ppm (SNO, n = 8). PSV level was varied to maintain a tidal volume of 8 to 10 ml/kg for another 12 h or unti l early animal death. Five animals in the SNO, three each in the NO and Sur f group, and one in the Control group survived 12 h (SNO versus Control, p < 0.05). The NO, Surf, and SNO groups had significantly improved mean Pa-O2 (> 70 mm Hg, p < 0.05), and reduced (Q) over dot s/(Q) over dot T (15, 19, and 17%, respectively, p < 0.05) at 6 and 12 h, but not in the Control gro up. The SNO group had the highest values of Cdyn at 12 h, alveolar aeration and disaturated phosphatidylcholine-to-total protein ratio in bronchoalveo lar lavage fluid, and the lowest wet-to-dry lung weight ratio and lung inju ry score (p < 0.05). The results indicate that early alleviation of ALI by surfactant, iNO, and PSV is due to synergistic effects, and only PSV in thi s model had limited effects.