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- Calkovska, A, et al.
(author)
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Biophysical and physiological properties of porcine surfactant enriched with polymyxin B
- 2005
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In: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 88:2, s. 101-108
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Journal article (peer-reviewed)abstract
- <i>Objective:</i> We examined whether the biophysical and physiological properties of Curosurf<sup>®</sup> were improved by the cyclic amphipathic decapeptide polymyxin B (PxB). <i>Methods:</i> Curosurf was diluted to 1–5 mg/ml with PxB added at 1, 2 or 3% (w/w). Albumin was added at 40 mg/ml. Minimum surface tension (γ<sub>min</sub>) during surface compression was determined for each mixture with pulsating bubble. Immature newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32 mg/ml with or without 2% PxB and ventilated for up to 5 h. <i>Results:</i> At surfactant concentration 2 mg/ml, γ<sub>min</sub> was high (17 ± 8.9 mN/m) but remained low (2.7 ± 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5 mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax in comparison with controls but had no significant effect on lung-thorax compliance or alveolar expansion. <i>Conclusion:</i> Addition of 2% PxB improves surface activity of Curosurf at low concentration, increases its resistance to inactivation by albumin, and reduces the incidence of pneumothorax in immature newborn rabbits undergoing prolonged ventilation.
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| 6. |
- Calkovska, A, et al.
(author)
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Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits
- 2016
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In: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 109:3, s. 177-185
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. <b><i>Objectives:</i></b> To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. <b><i>Methods:</i></b> Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated. <b><i>Results:</i></b> Treatment with Curosurf® or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (V<sub>T</sub>) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small V<sub>T</sub>, but after addition of both analogues V<sub>T</sub> was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-<i>sn</i>-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on V<sub>T</sub> and LGV as Curosurf. <b><i>Conclusions:</i></b> Phospholipid composition is important for V<sub>T</sub> while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding V<sub>T</sub> and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.
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| 9. |
- Calkovska, A, et al.
(author)
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Restoration of surfactant activity by polymyxin B in lipopolysaccharide-potentiated injury of immature rabbit lungs
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 22-
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Journal article (peer-reviewed)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.
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