Biophysical and Physiological Properties of Porcine Surfactant Enriched with Polymyxin B

Abstract

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 (γ_min) 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, γ_min 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.

Prophylactic Intratracheal Polymyxin B/Surfactant Prevents Bacterial Growth in Neonatal Escherichia coli Pneumonia of Rabbits

“…In the absence of LPS in vitro, the surfactant/PxB preparations showed increased resistance to surfactant inactivation with albumin or meconium (5,20). However, in the present investigation, addition of PxB resulted only in an inconsistent improvement in compliance (Tables 1 and 2).…”

Polymyxin B/Pulmonary Surfactant Mixtures Have Increased Resistance to Inactivation by Meconium and Reduce Growth of Gram-Negative Bacteria In Vitro

“…In the absence of meconium, PxB significantly reduced static surface tension only at 2.5 mg/mL Curosurf in the Wilhelmy balance, whereas no improvement was seen at 5 mg/mL or when identical samples were tested for static or dynamic surface tension in the PBS. Calkovska et al (19) found improved dynamic surface activity after addition of 2% PxB to Curosurf 2 mg/mL. We used slightly higher Curosurf concentrations and found, even without addition of PxB, ␥ min Ͻ3 mN/m.…”

“…Calkovska et al (19) suggested an increased resistance of Curosurf to albumin-induced inactivation in vitro after addition of PxB 2% (wt/wt), corresponding with 2-4 mg/kg body weight. For aerosolized free PxB, a maximum dose of 2.5 mg/kg/d divided in four doses is recommended for adults with normal renal clearance (35).…”

New Synthetic Surfactants – Basic Science

“…By addition of different components such as dextran [45,46] , polyethyleneglycol [46] , hyaluronan [47] or polymyxin [48] to surfactant preparations, the inhibition can be counteracted as shown by both in vitro and in vivo experiments. Furthermore, recent observations in our laboratory have shown that the function of SP-B can be mimicked in vitro by polymyxin B, a structurally different acylated peptide, which cross-links phospholipid vesicles by ionic interactions.…”

“…Furthermore, recent observations in our laboratory have shown that the function of SP-B can be mimicked in vitro by polymyxin B, a structurally different acylated peptide, which cross-links phospholipid vesicles by ionic interactions. Addition of 2% (w/w) of polymyxin B to the surfactant preparation increased the resistance of pulmonary surfactants to inactivation and improved their surface properties [48] . These data indicate that one of the functions of SP-B is to cross-link lipid vesicles and that this effect can be mimicked by a rather simple peptide.…”