Morphological alterations of exogenous surfactant inhibited by meconium can be prevented by dextran.
BACKGROUND
Surfactant dysfunction due to inhibition is involved in the pathophysiology of meconium aspiration syndrome. Dextran addition has been shown to reverse exogenous surfactant inactivation by meconium, but the precise mechanisms and the morphological correlate of this effect are yet unknown. Morphological surfactant analysis by transmission electron microscopy (TEM) and stereology allows the differentiation of active (large aggregates = LA) and inactive (small aggregates = SA) subtypes.


METHODS
To determine the in vitro effects of meconium and dextran addition on the morphology of a modified porcine natural surfactant (Curosurf), Curosurf samples were either incubated alone or together with meconium or with meconium and dextran, fixed and processed for TEM. Volume fractions of surfactant subtypes [lamellar body-like forms (LBL), multilamellar vesicles (MV), unilamellar vesicles (UV)] were determined stereologically.


RESULTS
All preparations contained LBL and MV (corresponding to LA) as well as UV (corresponding to SA). The volume fraction of UV increased with addition of meconium and decreased with further addition of dextran. Correspondingly, the UV/(LBL+MV) ratio (resembling the SA/LA ratio) increased when meconium was added and decreased when dextran was added to the surfactant-meconium mixture.


CONCLUSIONS
Meconium causes alterations in the ultrastructural composition of Curosurf that can be visualized and analyzed by TEM and stereology. These alterations resemble an increase in the SA/LA ratio and are paralleled by an increase in minimum surface tension. Dextran prevents these effects and may therefore be a useful additive to exogenous surfactant preparations to preserve their structural and functional integrity, thereby improving their resistance to inactivation.
Ochs
Matthias
M
Institute of Anatomy, Experimental Morphology, University of Bern, Baltzerstrasse 2, CH-3012 Bern, Switzerland. ochs@ana.unibe.ch
Schüttler
Markus
M
Stichtenoth
Guido
G
Herting
Egbert
E
D001688:Biological Products / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008470:Meconium / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010743:Phospholipids / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013500:Surface Tension
D001688:Biological Products; D003911:Dextrans; D010743:Phospholipids; D011663:Pulmonary Surfactants; C068291:poractant alfa