Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury.

Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C). Surfactant therapy consisted of two lung lavages (BAL) with diluted Curosurf (5 mg phospholipids/ml, 10 ml/kg) followed by undiluted Curosurf (100 mg phospholipids/kg). N-acetylcysteine (Acc Injekt, 10 mg/kg) was given intravenously in M + S + NAC group 10 min after surfactant therapy. Animals were oxygen-ventilated for additional 5 h. Then, differential white cell count in the blood (WBC) was determined. Left lung was saline-lavaged and differential cell count in BAL was determined. In right lung tissue, wet/dry weight ratio, oxidation markers (TBARS, 3NT) and interleukines (IL-2, IL-6, IL-13, and TNFα) using ELISA and RT-PCR were estimated. Combined S + NAC therapy significantly decreased W/D ratio, TBARS, 3NT, and IL, whereas the effect of monotherapies (either S or NAC) was less obvious. In conclusion, addition of NAC to surfactant treatment may enhance the therapeutic outcome in MAS.

High-Frequency Jet Ventilation against Small-Volume Conventional Mechanical Ventilation in the Rabbit Models of Neonatal Acute Lung Injury.

Patients with acute lung injury are ventilated by conventional mechanical ventilation (CMV) rather than high-frequency jet ventilation (HFJV). This study estimated the potential usefulness of HFJV in acute lung injury. The issue was addressed by comparing the effects on lung function of CMV and HFJV in two rabbit models of neonatal acute lung injury: repetitive saline lung lavage (LAV) and meconium aspiration syndrome (MAS) induced by intratracheal meconium instillation. The animals were then ventilated with either HFJV or CMV for 4 h. Ventilatory pressures, blood gases, and indexes of gas exchange were assessed. Lung edema formation was expressed as wet-dry lung weight ratio. Both LAV and MAS significantly decreased lung compliance, increased airway resistance, and caused severe hypoxemia, hypercarbia, and acidosis. Although CMV was superior to HFJV at 1 h of ventilation, there were no clinically relevant differences in lung function or edema formation between CMV and LAV in both models of respiratory insufficiency at 4 h of ventilation. We conclude that, HFJV may be used for ventilation in acute non-homogenous lung injury.

Effects on Lung Function of Small-Volume Conventional Ventilation and High-Frequency Oscillatory Ventilation in a Model of Meconium Aspiration Syndrome.

For treatment of severe neonatal meconium aspiration syndrome (MAS), lung-protective mechanical ventilation is essential. This study compared short-term effects of small-volume conventional mechanical ventilation and high-frequency oscillatory ventilation on lung function in experimentally-induced MAS. In conventionally-ventilated rabbits, MAS was induced by intratracheal instillation of meconium suspension (4 ml/kg, 25 mg/ml). Then, animals were ventilated conventionally with small-volume (f-50/min; VT-6 ml/kg) or with high frequency ventilation (f-10/s) for 4 h, with the evaluation of blood gases, ventilatory pressures, and pulmonary shunts. After sacrifice, left lung was saline-lavaged and cells in bronchoalveolar lavage fluid (BALF) were determined. Right lung was used for the estimation of lung edema formation (wet/dry weight ratio). Thiobarbituric acid-reactive substances (TBARS), oxidative damage markers, were detected in lung tissue and plasma. Meconium instillation worsened gas exchange, and induced inflammation and lung edema. Within 4 h of ventilation, high frequency ventilation improved arterial pH and CO2 elimination compared with conventional ventilation. However, no other significant differences in oxygenation, ventilatory pressures, shunts, BALF cell counts, TBARS concentrations, or edema formation were observed between the two kinds of ventilation. We conclude that high frequency ventilation has only a slight advantage over small-volume conventional ventilation in the model of meconium aspiration syndrome in that it improves CO2 elimination.