Comparison of functional efficacy of surfactant protein B analogues in lavaged rats.
Leakage of plasma proteins into the alveoli inhibits pulmonary surfactant function and worsens respiratory failure. Surfactant protein B (SP-B), is essential for surfactant function, but the N-terminal domain of human SP-B (residues 1.25, SP-B1-25) can mimic the biophysical properties of full length SP-B1-78 in vitro. The authors compared the function and inhibition resistance of synthetic surfactant preparations containing SP-B analogues to a natural bovine surfactant preparation "Survanta". Eight groups of eight rats were lavaged to induce surfactant deficiency, fibrinogen was instilled as a surfactant inhibitor, and then they were rescued with exogenous surfactant. Five experimental surfactants were formulated by mixing 3% SP-B1-78, or an equimolar amount of SP-B1-25 and/or 1% palmitoylated surfactant protein C (SP-C)1-35, into a standard phospholipid (PL) mixture: B1-78, B1-25, C1-35, B1-78+C1-35, and B1-25+C1-35 surfactant preparations. Survanta was used as a positive control and PL and no treatment as a negative control. Lung function was assessed during a 2-h period using arterial blood gas and lung compliance measurements. Rats treated with B1-25+C1-35 surfactant and Survanta maintained the highest oxygenation and lung compliance values throughout the experiments. The surfactants could be ranked as B1-25+C1-35 surfactant and Survanta >B1-25 and B1-78+C1-35 surfactants >others. Because the N-terminal domain of surfactant protein B1-25 can improve inhibition resistance, it may be able to substitute for surfactant protein B in exogenous surfactant preparations.
Gupta
M
M
Harbor-(University of California) Research and Education Institute, Torrance & Dept of Pediatrics, Charles R. Drew University of Medicine & Science, Los Angeles, USA.
Hernández-Juviel
J M
JM
Waring
A J
AJ
Bruni
R
R
Walther
F J
FJ
D000818:Animals; D001688:Biological Products; D018893:Bronchoalveolar Lavage; D004338:Drug Combinations; D008170:Lung Compliance / Q000187:drug effects*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D011510:Proteolipids / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001688:Biological Products; D004338:Drug Combinations; D010455:Peptides; D011498:Protein Precursors; D011510:Proteolipids; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; C489679:SFTPC protein, human; C105511:surfactant protein B propeptide; C077063:Sftpc protein, rat; C072197:beractant