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Research article - Peer-reviewed, 2021

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

Mikolka, Pavol; Curstedt, Tore; Feinstein, Riccardo; Larsson, Anders; Grendar, Marian; Rising, Anna; Johansson, Jan

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(R)), 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 TNF alpha, 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.

Keywords

ARDS model; CHF5633; inflammation; lung function; synthetic pulmonary surfactant

Published in

Physiological Reports
2021, volume: 9, number: 1, article number: e14700
Publisher: WILEY

Authors' information

Mikolka, Pavol
Karolinska Institutet
Curstedt, Tore
Karolinska University Hospital
Feinstein, Riccardo
National Veterinary Institute SVA
Larsson, Anders
Uppsala University
Grendar, Marian
Comenius University Bratislava
Karolinska Institutet
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)
Johansson, Jan
Karolinska Institutet

UKÄ Subject classification

Physiology

Publication Identifiers

DOI: https://doi.org/10.14814/phy2.14700

URI (permanent link to this page)

https://res.slu.se/id/publ/118681