Importance of hydrophobic apoproteins as constituents of clinical exogenous surfactants.
The biophysical properties and physiologic effects of a series of clinical exogenous pulmonary surfactants was compared to determine the importance of the hydrophobic apoproteins (SP-B and C) as constituents of these preparations. The three exogenous surfactants studied, calf lung surfactant extract (CLSE), Survanta (Surfactant-TA), and Exosurf, all contain dipalmitoyl phosphatidylcholine (DPPC) as their major constituent. CLSE and Survanta also contain 1 to 2% of SP-B,C but Exosurf has the additives hexadecanol and tyloxapol instead to enhance the activity of DPPC. In adsorption experiments, CLSE reached a final surface tension of 22 mN/m, and Survanta and Exosurf reached 28 and 38 mN/m, respectively. Addition of 1% by weight of an apoprotein isolate containing both SP-B and C to Exosurf slightly improved its adsorption. In oscillating bubble studies, CLSE and Survanta decreased surface tension to low values of less than 1 and 2 mN/m, respectively, but Exosurf achieved a minimum value of only 29 mN/m. Addition of SP-B,C to Exosurf improved this minimum to 1 mN/m and approached the behavior of mixtures of synthetic DPPC with SP-B,C. In both adsorption and pulsating bubble experiments, the minimum surface tensions found for Exosurf were almost identical to those generated by tyloxapol alone. In studies of physiologic activity, 20 mg of CLSE or Survanta restored the pressure-volume mechanics of lavaged, surfactant-deficient excised rat lungs to 95 and 50%, respectively, of normal prelavage levels. Instillation of Exosurf (37.5 mg) produced a minimal improvement of only 10% compared to 70% for mixtures containing 1% SP-B,C with either Exosurf or DPPC.(ABSTRACT TRUNCATED AT 250 WORDS)
Hall
S B
SB
Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Venkitaraman
A R
AR
Whitsett
J A
JA
Holm
B A
BA
Notter
R H
RH
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000493:pharmacokinetics; D000327:Adsorption; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001059:Apoproteins / Q000494:pharmacology*; D001688:Biological Products; D002417:Cattle; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D011510:Proteolipids / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D013500:Surface Tension; D013501:Surface-Active Agents / Q000494:pharmacology
D000418:Albumins; D001059:Apoproteins; D001688:Biological Products; D004338:Drug Combinations; D005233:Fatty Alcohols; D011510:Proteolipids; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D010767:Phosphorylcholine; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; C005031:cetyl alcohol; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; C072197:beractant; C016811:tyloxapol