Dextran or Polyethylene Glycol Added to Curosurf for Treatment of Meconium Lung Injury in Rats

Abstract

Background: In experimental lung injuries, improvement of lung function after treatment with surfactant/polymer mixtures may depend on both type of polymer and the specific surfactant. In vitro studies suggest that dextran is more effective when mixed with Curosurf, and polyethylene glycol (PEG) is more effective when mixed with Survanta. We therefore wanted to find out whether these results held true in an animal model of acute lung injury. Objective:To compare the response to therapy of PEG vs. dextran when added to Curosurf after meconium lung injury. Methods:Lung injury was produced by intratracheal instillation of meconium (30 and 4 ml/kg). One hour after injury, Curosurf (35 mg/ml) with or without 5% dextran (68 kDa) or 5% PEG (10 kDa) was given. Arterial blood gases and peak inspiratory pressures were measured for 3 h after treatment while animals were supported by volume-regulated ventilation. Then animals were sacrificed and pressure volume relationships, lung wet/dry weights, and histology were assessed. Results:Initially, improved PaO₂ and inspiratory pressure occurred for both Curosurf/PEG and Curosurf/dextran groups compared with Curosurf, but at three hours, peak inspiratory pressure and PaO₂ remained significantly improved for the Curosurf/dextran but not for Curosurf/PEG groups when compared with Curosurf alone. Total lung capacity at the end of the experiment was also significantly increased in the Curosurf/dextran group, but not the Curosurf/PEG group when compared with Curosurf. Conclusion:Under these experimental conditions, Curosurf/dextran mixtures provided a better therapeutic response than Curosurf/PEG or Curosurf.

Bronchoalveolar lavage with pulmonary surfactant/dextran mixture improves meconium clearance and lung functions in experimental meconium aspiration syndrome

“…The harmful effect of meconium can be counterbalanced by increasing surfactant concentration [27] and/or enrichment of the surfactant preparations with polymers such as polyethylene glycol (PEG) [16,29], dextran [30], hyaluronan [17] and other substances [1,25]. Dextran is known to improve the activity of pulmonary surfactant in the presence of meconium in vitro [30] and restore the surface activity of modified natural surfactants by meconium in animal studies [18,31]. Positive effects of dextran on surfactant function were also demonstrated in models other than MAS [5,12].…”

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

“…Both in vitro (1)(2)(3)(4)(5)(6) and in vivo (7)(8)(9) trials have shown that these nonionic polymers can significantly improve the surface activity of different therapeutic lung surfactants and effectively reverse inactivation due to a variety of inhibitory substances.…”

Efeitos da adição de polietilenoglicol ao surfactante exógeno no tratamento da síndrome de aspiração de mecônio em coelhos recém-nascidos

“…Porém em outro estudo mais recente os autores não encontram diferenças na curva P-V de animais tratados com Curosurf ® ou Curosurf ® adicionado de PEG (Lu et al, 2005b (Dehority et al, 2005;Lu et al, 2005b).…”

“…Por fim não julgamos necessária a inclusão de um grupo de estudo que recebesse apenas o PEG, pois diversos estudos mostram que o polímero administrado de forma isolada no alvéolo não tem nenhum efeito, com comportamento igual à salina (Lu et al, 2000;2001a;2005b).…”

“…O frasco contendo a mistura final foi energicamente homogeneizado, utilizando-se um "mixer" (Mistral -Labline instruments INC, Melrose, Estados Unidos) por um período mínimo de 30 segundos, em temperatura ambiente, obtendo-se uma mistura final homogênea, sem grumos visíveis a olho nu. A forma de preparo e mistura do PEG foi realizada seguindo técnica descrita na literatura (Lu et al, 2001a;Lu et al, 2005b).…”