Impact of synthetic surfactant CHF5633 with SP-B and SP-C analogues on lung function and inflammation in rabbit model of acute respiratory distress syndrome.

Abstract

Acute respiratory distress syndrome (ARDS) is associated with diffuse inflammation, alveolar epithelial damage, and leakage of plasma proteins into the alveolar space, which together contribute to inactivation of pulmonary surfactant and respiratory failure. Exogenous surfactant delivery is therefore considered to hold potential for ARDS treatment, but clinical trials with natural derived surfactant or synthetic surfactant containing a surfactant protein C (SP-C) analogue have been negative. Synthetic surfactant CHF5633, containing analogues of SP-B and SP-C, may be effective against ARDS. The aim here was to compare treatment effects of CHF5633 and animal-derived surfactant poractant alfa in animal model of ARDS. ARDS was induced in adult New Zealand rabbits by mild lung lavages followed by injurious ventilation until respiratory failure (P/F ratio <26.7 kPa). The animals were then treated with intratracheal bolus of 200 mg/kg CHF5633 or poractant alfa (Curosurf® ), or air as control. The animals were subsequently ventilated for an additional 4 hr and respiratory parameters were recorded regularly. Postmortem, histological analysis, degree of lung edema, and levels of the cytokines TNFα, IL-6, and IL-8 in lung homogenates were evaluated. Both surfactant preparations improved lung function, reduced the levels of pro-inflammatory cytokines, and degree of lung edema to very similar degrees versus the controls. No significant differences in any of the analyzed parameters were observed between the CHF5633- and poractant alfa-treated groups. This study indicates that single dose of CHF5633 improves lung function and attenuates inflammation as effectively as poractant alfa in experimental ARDS caused by injurious ventilation.

• Authors: Pavol Mikolka, Tore Curstedt, Riccardo Feinstein, Anders Larsson, Marian Grendar, Anna Rising, Jan Johansson
• Journal: Physiological reports (Physiol Rep) Vol. 9 Issue 1 Pg. e14700 (01 2021) ISSN: 2051-817X [Electronic] United States
• PMID: 33403805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Biological Products
• CHF5633
• Peptide Fragments
• Phosphatidylcholines
• Phospholipids
• Pulmonary Surfactant-Associated Protein B
• Pulmonary Surfactant-Associated Protein C
• Pulmonary Surfactants
• poractant alfa

Topics

• Animals
• Biological Products (pharmacology)
• Disease Models, Animal
• Inflammation (drug therapy, pathology)
• Lung (drug effects, pathology)
• Peptide Fragments (pharmacology)
• Phosphatidylcholines (pharmacology)
• Phospholipids (pharmacology)
• Pulmonary Surfactant-Associated Protein B (metabolism, pharmacology)
• Pulmonary Surfactant-Associated Protein C (metabolism, pharmacology)
• Pulmonary Surfactants (pharmacology)
• Rabbits
• Respiratory Distress Syndrome (drug therapy, metabolism, pathology)