Mitigation of endotoxin-induced acute lung injury in ventilated rabbits by surfactant and inhaled nitric oxide.

Abstract

To evaluate the efficacy of surfactant and inhaled nitric oxide (iNO) in endotoxin-induced acute lung injury (ALI). Prospective, randomised, controlled experimental study. A medical university hospital research laboratory. Twenty-nine adult rabbits (2.4-3.4 kg) were given two doses of intravenous endotoxin (Escherichia coli) (0.01 mg/kg and, 12 h later, 0.1 mg/kg), and then subjected to mechanical ventilation. After 8 h these animals were allocated to four treatment groups: (1) control, (2) iNO at 20 ppm (NO), (3) surfactant at 100 mg/kg (Surf) and (4) both surfactant and iNO as in groups 2 and 3 (SNO), and ventilated for a further 6 h followed by broncho-alveolar lavage (BAL), analysis of surfactant contents in BAL fluid and histological examination of the lungs. All the animals had developed ALI with respiratory failure 8 h after the second dose of endotoxin as evidenced by a decrease of PaO2/FIO2 from 520 +/- 30 to 395 +/- 19 mmHg and dynamic compliance (Cdyn) from 1.20 +/- 0.11 to 0.73 +/- 0.05 ml/ cmH2O x kg, and an increase of intrapulmonary shunting (Qs/Qt) from 7.5 +/- 0.8% to 12.9 +/- 1.0% (all measurements p < 0.01 versus baseline). In the SNO group, values for PaO2/FIO2, Cdyn and Qs/Qt after 6 h were 301 +/- 15 mmHg, 0.67 +/- 0.05 ml/cmH2O x kg and 16.5 +/- 0.8%, compared to 224 +/- 26 mmHg, 0.53 +/- 0.04 ml/ cmH2O x kg and 24.1 +/- 2.0%, respectively, in the control group (all measurements p < 0.01). Both Surf and NO groups showed intermediate levels of these parameters. In both Surf and SNO groups, the minimum surface tension of BAL fluid was lower, and the content of disaturated phosphatidylcholine/total protein higher, than in the control and NO groups (p < 0.01). Histological features of lung injury were less prominent and wet/dry lung weight ratio lower in the NO, Surf and SNO groups. Decreased surfactant protein A (SP-A) and its mRNA expression were found in all endotoxin-exposed groups, but the SP-A content of the SNO group was moderately improved in comparison to the control group. Surfactant aggregate size was not affected. Early application of surfactant and iNO moderately mitigated ALI as reflected by improvement of lung mechanics, pulmonary perfusion and morphology.