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Biophysical and physiological properties of porcine surfactant enriched with polymyxin B
A Calkovska1, M Some, B Linderholm
1Laboratory for Surfactant Research, Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden.
Objective:
We examined whether the biophysical and physiological properties of Curosurf were improved by the cyclic amphipathic decapeptide polymyxin B (PxB).
Methods:
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 (gammamin) 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.
Results:
At surfactant concentration 2 mg/ml, gammamin 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.
Conclusion:
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.
Insights
Polymyxin B (PxB) enhances Curosurf's surface activity and resistance to albumin inactivation. This combination reduced pneumothorax incidence in newborn rabbits, improving respiratory support outcomes.
Area of Science:
- Biochemistry
- Pulmonary Medicine
- Neonatology
Background:
- Curosurf is a vital exogenous surfactant for treating respiratory distress syndrome.
- Exogenous surfactant therapy can be limited by factors like albumin inactivation.
- Polymyxin B (PxB) is a cyclic peptide with potential to modify surfactant properties.
Purpose of the Study:
- To investigate the effects of Polymyxin B (PxB) on the biophysical and physiological properties of Curosurf.
- To assess PxB's ability to improve Curosurf's performance and stability.
Main Methods:
- Curosurf was mixed with varying concentrations of PxB (1-3%) and albumin (40 mg/ml).
- Minimum surface tension was measured using a pulsating bubble surfactometer.
- Immature newborn rabbits received Curosurf with or without PxB and were mechanically ventilated.
Main Results:
- PxB significantly reduced minimum surface tension of Curosurf at low concentrations.
- 2% PxB prevented albumin-induced inactivation of Curosurf.
- PxB-treated Curosurf reduced pneumothorax incidence in ventilated newborn rabbits.
Conclusions:
- Polymyxin B (PxB) improves Curosurf's surface activity and albumin resistance.
- The addition of PxB to Curosurf shows promise for reducing complications in neonatal respiratory support.
- Further research is warranted to explore PxB's full therapeutic potential in surfactant replacement therapy.
