Protein composition of synthetic surfactant affects gas exchange in surfactant-deficient rats.
Synthetic surfactant peptides offer an opportunity to standardize the protein composition of surfactant. We tested the effect of phospholipids (PL) with synthetic full-length SP-B1-78 (B), mutant B (Bser), KL4 peptide (UCLA-KL4), and palmitoylated SP-C1-35 (C) on oxygenation and lung function in a surfactant-deficient rat model. Sixty-four adult rats were ventilated with 100% oxygen, a tidal volume of 7.5 mL/kg, and a rate of 60/min. Their lungs were lavaged with saline until the arterial PO2 dropped below 80 torr, when 100 mg/kg surfactant was instilled. Surfactant preparations included: PL (PL surfactant), PL + 3% B (B surfactant), PL + 3% B and 1% C (BC surfactant), PL + 3% UCLA-KL4 (KL4 surfactant), PL + 3% Bser (Bser surfactant), and PL + 3% B and 1% UCLA-KL4 (BKL4 surfactant). Sixty minutes after surfactant instillation, positive end-expiratory pressure was applied for 5 min, and pressure-volume curves were determined in situ. The six surfactant preparations had a minimum surface tensions <10 mN/m on a Langmuir/Wilhelmy balance. Instillation of PL, Bser, and BKL4 surfactant increased mean arterial/alveolar PO2 (aADO2) ratios by 50-100% over postlavage values, whereas KL4 surfactant increased aADO2 ratios by 118%, B surfactant by 191%, and BC surfactant by 225%. Lung volumes at 30 cm H2O pressure were highest after treatment with BC surfactant, intermediate after B and KL4 surfactants, and lowest after BKL4, Bser, and PL surfactants. These data suggest that a surfactant preparation with a combination of synthetic B and C peptides surpasses synthetic B and KL4 surfactants in improving oxygenation and lung compliance in surfactant-deficient rats.
Walther
F J
FJ
Department of Pediatrics, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.
Hernández-Juviel
J
J
Bruni
R
R
Waring
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology; D011510:Proteolipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D007507:Therapeutic Irrigation; D013990:Tidal Volume
D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D010446:Peptide Fragments; D010455:Peptides; D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants