Comparison of functional efficacy of surfactant protein B analogues in lavaged rats.

Abstract

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.