Abstract
During postnatal adaptation pulmonary surfactant may be inactivated by lipopolysaccharide (LPS). We evaluated the effect of surfactant therapy in combination with antibiotic polymyxin B (PxB) in double-hit model of neonatal lung injury. Surfactant (poractant alfa, Curosurf) was exposed to smooth (S) LPS without/with PxB and tested in captive bubble surfactometer. Preterm rabbits received intratracheally saline (control) or S-LPS and were ventilated with 100% oxygen. After 30 min, LPS-treated animals received no treatment, or surfactant (200 mg/kg) without/with 3% PxB; controls received the same dose of surfactant. Animals were ventilated for further 2 h. In vitro, addition of 5% S-LPS to surfactant increased minimum surface tension (γmin) and addition of 1–3% PxB to surfactant/S-LPS mixture restored γmin to low values. Animals only given S-LPS had lower lung compliance and lung gas volume (LGV) compared to surfactant groups. Treatment with surfactant/PxB, but not with surfactant only, restored LGV. Addition of PxB to the surfactant increased the alveolar expansion. S-LPS interferes with surface activity of the pulmonary surfactant and PxB improves the resistance of surfactant to LPS-induced inactivation. In our neonatal model of respiratory distress syndrome surfactant gives positive response even in simultaneous exposure to S-LPS, when enriched with PxB.
Highlights
The interface between respiratory system and external environment is permanently exposed to the air- or bloodborne toxins
Different concentrations of poractant alfa were tested in order to find the lowest concentration of PL at which the surfactant had a minimum surface tension ≤ 5 mN/m during the 5th cycle in the captive bubble surfactometer and was sensitive to inactivation by LPS
LPS interferes with surface-active properties of the pulmonary surfactant and prevents the alveoli from reaching low surface tension during expiration
Summary
The interface between respiratory system and external environment is permanently exposed to the air- or bloodborne toxins. PxB is the antimicrobial peptide used in clinical practice to treat infections by resistant Gram-negative bacteria It binds Escherichia coli lipopolysaccharides and prevents inflammatory a ctivation[15]. It mimics some activities of a specific surfactant protein B 16, stabilizes surfactant multilayers and is able to increase the resistance of exogenous surfactant to serum albumin17, meconium[14] and LPS in vitro[18]. Surfactant/PxB mixture has been effective in animals with acute respiratory distress syndrome due to albumin leak[17] and prevented bacterial growth in neonatal E. coli pneumonia of rabbits[20], but has not been evaluated in other models of neonatal lung disease. The aims of the present study were to investigate, in captive bubble surfactometer, the interplay between surfactant, smooth LPS and PxB and to evaluate in a newly established double-hit neonatal rabbit model connecting lung immaturity and inflammatory response, the effect of PxB for restoring surfactant activity
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