Am. J. Respir. Crit. Care Med., Vol 150, No. 4, 10 1994, 918-923.
In vivo function of surfactants containing phosphatidylcholine analogs
L Dizon-Co, M Ikegami, T Ueda, AH Jobe, WH Lin, JG Turcotte, RH Notter and ED Rider
Perinatal Research Laboratories, Harbor-UCLA Medical Center, UCLA School of Medicine.
Increased phospholipase A2 activity demonstrated in some forms of lung
injury may contribute to surfactant dysfunction. Phospholipase A2-
resistant analogs of dipalmitoylphosphatidylcholine (DPPC) with surfactant
properties might therefore be useful lipid components of treatment
surfactants for certain lung injuries. The in vivo function of surfactants
containing DPPC or the phospholipase-resistant analogs
dihexadecylphosphatidylcholine (DEPC) or dihexadecylphosphonotidylcholine
(DEPnC), with or without surfactant proteins B and C (SP-B+C), was thus
evaluated in preterm rabbits (27 days' gestation). Rabbits randomly
received one of seven surfactants (DPPC, DEPC, DEPnC, DPPC+SP-B+C,
DEPC+SP-B+C, DEPnC+SP-B+C, or lipid extract surfactant [LES]) or 0.45% NaCl
(control) and were ventilated for 30 min. Lipid-only surfactants decreased
ventilatory pressures (peak inspiratory pressures minus positive
end-expiratory pressure) relative to control (p < 0.05). Addition of
SP-B+C further decreased ventilatory pressures to levels similar to LES (p
< 0.01 versus control, lipid-only surfactants). Lung dynamic compliances
and postventilation pressure-volume curves improved in the following order:
LES, SP-B+C lipid surfactants > lipid-only surfactants > control (p
< 0.05). All surfactant preparations decreased intravascular
125I-albumin recoveries in the lungs relative to control (p < 0.01 for
all surfactants versus control). These results indicate that DEPC and DEPnC
were as effective as DPPC as lipid components of synthetic surfactants. And
like DPPC, the analogs interacted with isolated SP-B+C and improved in vivo
function to levels comparable to LES.