[Influence of inhaled nitric oxide on surfactant in the total cardiopulmonary bypass pig model].

OBJECTIVE

To study whether or not inhaled nitric oxide (INO) can improve surfactant production and pulmonary mechanics after CPB in pigs, and to seek the mechanism of lung injury during mechanical ventilation.

METHODS

Thirty pigs were randomized into 6 groups: Sham (n = 5), Sham + INO (n = 5), CPB (n = 5), CPB + INO (n = 5), CPB + lipopolysaccharide (LPS) (n = 5), and CPB + LPS + INO (n = 5). After anesthesia induction, INO (mass fraction, 20 x 10(-6)), added to the gas mixture, was given to the animals throughout the procedure. After 2 hours of INO treatment, broncho-alveolar lavage (BAL) fluid was taken for surfactant assay and cytology analysis. Pulmonary hemodynamics parameters and lung compliance were measured as well. CPB was performed for 90 minutes after the first BAL sampling at T0. Four hours (T4) and 24 hours (T24) following CPB, BAL and other measurements were repeated. After CPB, LPS (4 micrograms.kg-1) was infused to specific groups of pigs within 90 minutes in order to stimulate the inflammation process.

RESULTS

Pulmonary hemodynamics parameters (pulmonary artery pressure, pulmonary vascular resistance and oxygenation) in all INO groups were much better than those of the control groups at T4 and T24. However, lung compliance of pigs in all groups declined with time, and showed statistically significant differences at T24 compared with T0. At T0, the active subfraction of surfactant (large aggregate, LA) was increased in animals given INO treatment compared with the controls, but decreased with time, and at T24 significantly reduced in all groups. In LPS groups, this decrease LA after T4 was very obvious. Total cell counts and the percent differentials of neutrophils in BAL increased with time, being lower in the INO groups than in other groups.

CONCLUSION

INO exposure exerted time-related effects on the lung surfactant (LA). Initially, INO resulted in short-term increase of surfactant production at T0. However, with time passing by, INO exposure following CPB did not prevent long-term decrease of lung surfactant and lung compliance although INO was beneficial for pulmonary hemodynamics and oxygenation. In summary, despite the use of INO, synergetic effects of long-term hyperoxia, mechanical ventilation and inflammation following CPB may exacerbate pulmonary mechanics and result in surfactant dysfunction.