4.3 Article

Therapeutic effects of exogenous surfactant enriched with dextran in newborn rabbits with respiratory failure induced by airway instillation of albumin

Journal

PULMONARY PHARMACOLOGY & THERAPEUTICS
Volume 21, Issue 2, Pages 393-400

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pupt.2007.10.003

Keywords

ARDS; Albumin; Lung compliance; Pulmonary surfactants; Dextran

Funding

  1. Swedish Research Council [3351, 10371]
  2. Konung Oscar II's Jubilcumsfond
  3. Research Funds of the Karolinska Institute
  4. Chiesi Farmaceutici
  5. European Respiratory Society

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The aim of the study was to investigate lung function and morphology in newborn rabbits with acute respiratory failure induced by airway instillation of albumin and to test whether the therapeutic effect of exogenous modified natural surfactant could be enhanced by addition of dextran. Rabbits (gestational age 29 days) were ventilated with 100% O-2 and tidal volume 8-10 ml/kg. Respiratory failure was induced by tracheal instillation of albumin (50 or 100 mg/ml; 2 ml/kg) and the instillation was repeated 15 min later. Surfactant (Curosurf, 200 mg/kg) with or without addition of dextran (30 mg/ml) was administered 15 min after the second dose of albumin and animals were then ventilated for another 60 min. In one series of experiments, instillation of albumin was followed by administration of diluted Curosurf (40 mg/kg) with or without dextran (30 mg/ml). Animals with initial lung-thorax compliance (C-LT)<0.6 ml/kg cm H2O were directly treated with surfactant without previous instillation of albumin. Animals treated with a larger dose of Curosurf (200 mg/kg) showed a significant increase in C-LT at 60 min with no difference between groups receiving high or low dose of albumin. Addition of dextran to Curosurf at high dose (200 mg/kg) reduced the therapeutic response (P<0.05 vs. Curosurf without dextran). After treatment with low-dose Curosurf (40 mg/kg) C-LT increased more prominently after Curosurf+dextran than after non-enriched surfactant (P<0.05). Dextran potentiated the treatment effect of Curosurf at suboptimal dose (40 mg/kg) but not at high dose (200 mg/kg) in animals with low-grade surfactant deficiency or respiratory failure induced by airway instillation of albumin. (C) 2007 Elsevier Ltd. All rights reserved.

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