title: Prevention of rabbit acute lung injury by surfactant, inhaled nitric oxide, and pressure support ventilation.
abstract: Improvement of pulmonary perfusion and blood oxygenation and prevention of acute lung injury (ALI) may rely on ventilation strategy. We hypothesized that application of a combined surfactant, inhaled nitric oxide (iNO), and pressure 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 intravenously (60 microl/kg). Within 90 min this caused a reduction of Pa(O(2)) 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 H(2)O/kg (both p < 0.01), and increase of intrapulmonary shunting (Q S/Q T) from 9.4 +/- 1.2 to 27 +/- 5% (p < 0.05). PSV was subsequently applied with 3 cm H(2)O of continuous positive airway pressure and FI(O(2)) of 0.3, and the animals were randomly allocated to four groups, receiving: (1) PSV only (Control, n = 10); (2) iNO at 20 ppm (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 until early animal death. Five animals in the SNO, three each in the NO and Surf 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(O(2)) (> 70 mm Hg, p < 0.05), and reduced Q S/Q T (15, 19, and 17%, respectively, p < 0.05) at 6 and 12 h, but not in the Control group. The SNO group had the highest values of Cdyn at 12 h, alveolar aeration and disaturated phosphatidylcholine-to-total protein ratio in bronchoalveolar lavage fluid, and the lowest wet-to-dry lung weight ratio and lung injury 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 this model had limited effects.
authors.affiliation: Children's Hospital Research Institute, Shanghai Medical University, Shanghai, Peoples Republic of China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Sun
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.forename: L W
authors.initials: LW
authors.lastname: Zhu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015633:Extravascular Lung Water / Q000187:drug effects; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D009569:Nitric Oxide / Q000494:pharmacology*; D011175:Positive-Pressure Respiration; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000517:prevention & control*
chemical_list: D011663:Pulmonary Surfactants; D009569:Nitric Oxide