In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant ( 14 C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 Ϯ 10% (mean Ϯ SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml ⅐ cm H 2 O Ϫ1 ⅐ kg Ϫ1, respectively; p Ͻ 0.05). The relative distribution of 14 C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 Ϯ 4 versus 26 Ϯ 3% (mean Ϯ SEM)] than in mechanically ventilated animals (p Ͻ 0.01), the latter figure being very similar to that of the control group (25 Ϯ 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation. In neonates with respiratory distress syndrome (RDS), exogenous surfactant has become a standard treatment (1). In humans, the effective mode of administration is instillation into the airways. This requires intubation, which means that surfactant treatment is usually given in conjunction with mechanical ventilation. With increasing knowledge of the detrimental effects of mechanical ventilation on the immature lung, there is a need for alternative treatment approaches. Early nasal continuous positive airway pressure (nCPAP) has been shown to be beneficial as initial treatment of RDS also in very low birth weight infants (2,3). With the administration of exogenous surfactant during a short intubation, followed by immediate extubation to nCPAP, the need for mechanical ventilation is reduced in preterm infants with RDS (4,5). In most of these patients, a single dose of surfactant is sufficient to reverse the clinical course of RDS, whereas in mechanically ventilated infants, multiple doses are often required (6). On the basis of these clinical observations, we hypothesized that the duration of the treatment response would be better and more sustained if infants were allowed to breathe spontaneously after receiving s...

In periodontitis local bacteria might stimulate PMN to release ROS, which cause inflammation and destruction.

Production of oxygen radicals by stimulated phagocytes followed by surfactant lipid peroxidation (LPO) and loss of surfactant function have all been implicated in the pathogenesis of acute lung injury. We studied the interactions between natural lung surfactant (Curosurf) and neutrophils in vitro, and compared various antioxidants; (superoxide dismutase (SOD), vitamin E, vitamin C, ebselen and melatonin), or combinations of them in duplicate and triplicate regarding their ability to decrease superoxide production and the peroxidation level of surfactant caused by activated phagocytes. The superoxide production of neutrophils activated by Candida albicans was measured with the nitroblue tetrazolium (NBT) test. The subsequent LPO was estimated as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). We found that lung surfactant decreased the superoxide production by activated neutrophils (29.7%) and that Curosurf was peroxidized with elevated MDA/4-HNE values. With supplements of antioxidants (except vitamin C), superoxide radical production and the surfactant LPO level fell in a dose-dependent manner. The protective effect of the antioxidants differed in each test. SOD had a slight effect in both tests. The findings with vitamin E, melatonin and ebselen were similar. The best combination was that of a natural and a synthetic antioxidant (melatonin-ebselen) with a 60% decrease in comparison to the corresponding control. These findings suggest that antioxidants, particularly in combination, prevent LPO of lung surfactant.