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

Abstract

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% O2 and tidal volume 8-10 ml/kg. Respiratory failure was induced by tracheal instillation of albumin (50 or 100mg/ml; 2 ml/kg) and the instillation was repeated 15 min later. Surfactant (Curosurf, 200mg/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 (CLT)<0.6 ml/kg cm H2O were directly treated with surfactant without previous instillation of albumin. Animals treated with a larger dose of Curosurf (200mg/kg) showed a significant increase in CLT at 60 min with no difference between groups receiving high or low dose of albumin. Addition of dextran to Curosurf at high dose (200mg/kg) reduced the therapeutic response (P<0.05 vs. Curosurf without dextran). After treatment with low-dose Curosurf (40 mg/kg) CLT 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 (200mg/kg) in animals with low-grade surfactant deficiency or respiratory failure induced by airway instillation of albumin.

• Authors: A Calkovska, M Some, B Linderholm, T Curstedt, B Robertson
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 21 Issue 2 Pg. 393-400 ( 2008) ISSN: 1094-5539 [Print] England
• PMID: 18032077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biological Products
• Dextrans
• Phospholipids
• Pulmonary Surfactants
• Serum Albumin
• poractant alfa

Topics

• Acute Disease
• Animals
• Animals, Newborn
• Biological Products (administration & dosage, therapeutic use)
• Dextrans (administration & dosage, therapeutic use)
• Drug Synergism
• Drug Therapy, Combination
• Gestational Age
• Humans
• Lung Compliance (drug effects)
• Phospholipids (administration & dosage, therapeutic use)
• Pulmonary Surfactants (administration & dosage, therapeutic use)
• Rabbits
• Respiratory Insufficiency (chemically induced, drug therapy, pathology)
• Serum Albumin