Sensitivity of synthetic surfactants to albumin inhibition in preterm rabbits.
Surfactant can be inhibited in vivo by plasma proteins invading the alveolar space during acute lung injury. The resistance to protein inhibition of surfactant preparations with various synthetic surfactant proteins B and C (B and C) was tested in preterm rabbits. Surfactants consisted of a palmitic acid containing phospholipid mixture (PL) with full-length SP-B peptide (B1-78), one of two SP-B mutants (Bserine and BR236C), the synthetic SP-B mimic KL4 (UCLA-KL4), a natural SP-B (Bbovine), synthetic palmitoylated SP-C peptide (C1-35), a combination of B1-78 + C1-35, a combination of BR236C + C1-35, and the clinical surfactant Survanta. Preterm rabbits born at 28 days of gestation were ventilated and received 100 mg/kg of albumin intratracheally at 30 min and 100 mg/kg of surfactant at 45 min after birth. Dynamic lung compliance (tidal volume/mean airway pressure) decreased from 0.82 to 0.57 mL/kg/cm H2O after albumin instillation and to 0.43 mL/kg/cm H2O over a 60-min period after saline placebo. Treatment with B1-78 + C1-35 and BR236C + C1-35 surfactant and Survanta returned dynamic compliance to prealbumin values, B1-78, BR236C, Bbovine, and C1-35 surfactant stabilized dynamic compliance, but PL, Bserine, and UCLA-KL4 surfactant were unable to prevent a further deterioration in dynamic compliance. These data suggest that a combination of synthetic surfactant peptides B1-78 and C1-35 and the clinical surfactant Survanta confer a high degree of resistance to surfactant inhibition by human albumin in ventilated preterm rabbits.
Mbagwu
N
N
Department of Pediatrics, Charles R. Drew University of Medicine and Science, Los Angeles, California.
Bruni
R
R
Hernández-Juviel
J M
JM
Waring
A J
AJ
Walther
F J
FJ
D000818:Animals; D000831:Animals, Newborn; D001696:Biomechanical Phenomena; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D011817:Rabbits; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000494:pharmacology*; D013499:Surface Properties / Q000187:drug effects