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- Almlen, A, et al.
(författare)
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Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity
- 2007
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 92:3, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5–1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development. <i>Objectives:</i> To investigate the potential of different concentrations of the SP-C analogue SP-C33 in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol (68:31, w/w). <i>Methods:</i> Surface activity was evaluated in pulsating and captive bubble surfactometers and in immature newborn rabbits. <i>Results:</i> Preparations containing ≧1% SP-C33 achieve minimum surface tension <5 mN/m indicating good biophysical activity, and increase tidal volumes in premature rabbit fetuses to the same level as a modified natural surfactant preparation does. Alveolar patency at end expiration, as evaluated by measurement of lung gas volumes, histological assessment of alveolar expansion and determination of alveolar volume density, was lower in the animals treated with synthetic surfactant than in those receiving modified natural surfactant. <i>Conclusions:</i> These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.
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- Almlen, A, et al.
(författare)
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Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome
- 2008
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 104:4, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of ∼5 ml/kg after 30 min of ventilation. However, treatment with phospholipids containing both SP-B and SP-C/SP-C33 approximately doubled lung gas volumes. Doubling the SP-C33 content did not affect lung gas volumes. The tidal volumes were similar in all groups receiving surfactant. This shows that SP-B and SP-C exert different physiological effects, since both proteins are needed to establish alveolar stability at end expiration in this animal model of respiratory distress syndrome, and that an optimal synthetic surfactant probably requires the presence of mimics of both SP-B and SP-C.
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- Almlen, A, et al.
(författare)
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Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits
- 2010
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 98:1, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. <i>Objectives:</i> To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. <i>Methods:</i> Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. <i>Results:</i> Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8–9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3–4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15–17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. <i>Conclusions:</i> The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
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- Johansson, J, et al.
(författare)
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A synthetic surfactant based on a poly-Leu SP-C analog and phospholipids: effects on tidal volumes and lung gas volumes in ventilated immature newborn rabbits
- 2003
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Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 95:5, s. 2055-2063
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Tidskriftsartikel (refereegranskat)abstract
- Available surfactants for treatment of respiratory distress syndrome in newborn infants are derived from animal lungs, which limits supply and poses a danger of propagating infectious material. Poly-Val→poly-Leu analogs of surfactant protein (SP)-C can be synthesized in large quantities and exhibit surface activity similar to SP-C. Here, activity of synthetic surfactants containing a poly-Leu SP-C analog (SP-C33) was evaluated in ventilated premature newborn rabbits. Treatment with 2.5 ml/kg body wt of 2% (wt/wt) SP-C33 in 1,2-dipalmitoyl- sn-3-glycero phosphoryl choline (DPPC)-1-palmitoyl-2-oleoyl- sn-3-glycero phosphoryl choline (POPC)-1-palmitoyl-2-oleoyl- sn-3-glycero phosphoryl glycerol (POPG), 68:0:31, 68:11:20, or 68:16:15 (wt/wt/wt) suspended at 80 mg/ml gave tidal volumes (Vt) of 20-25 ml/kg body wt, with an insufflation pressure of 25 cmH2O and no positive end-expiratory pressure (PEEP), comparable to the Vt for animals treated with the porcine surfactant Curosurf. Nontreated littermates had a Vt of ∼2 ml/kg body wt. The Vt for SP-C33 in DPPC-egg phosphatidylglycerol-palmitic acid [68:22:9 (wt/wt/wt)], DPPC-POPG-palmitic acid [68:22:9 (wt/wt/wt)], and DPPC-POPC-POPG [6:2:2 (wt/wt/wt)] was 15-20 ml/kg body wt. Histological examination of lungs from animals treated with SP-C33-based surfactants showed incomplete, usually patchy air expansion of alveolar spaces associated with only mild airway epithelial damage. Lung gas volume after 30 min of mechanical ventilation were more than threefold larger in animals treated with Curosurf than in those receiving SP-C33 in DPPC-POPC-POPG, 68:11:20. This difference could be largely counterbalanced by ventilation with PEEP (3-4 cmH2O). An artificial surfactant based on SP-C33 improves Vt in immature newborn animals ventilated with standardized peak pressure but requires PEEP to build up adequate lung gas volumes.
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