Surfactant substitution

Abstract

A mixture of synthetic phospholipids containing 90% Dipalmitoylphosphatidylcholine and 10% Dipalmitoylphosphatidylglycerol was tested for its suitability as surfactant substitute. Different methods of preparation were employed. The substance was studied by chromatography, Wilhelmy balance, and in rabbits after tracheal instillation during mechanical ventilation. When prepared as suspension of multilamellar liposomes in NaCl, the phospholipid samples displayed the essential surfactant features of adsorption from the subphase, spreading to a monolayer and lowering the surface tension to 3.7 dyn/cm at compression. For a dose of 2.55 microgram/cm2, the stability index was 1.83 +/- 0.29. Samples prepared with ultrasound were not surface-active. Sonication also destroyed the surface-tension-lowering ability of previously active samples. No signs of local toxicity were found in the treated animals. When radioactive DPPC/DPPG was instillated into the trachea of the ventilated rabbit, autohistoradiography demonstrated radioactive material in the alveoli covering the alveolar wall with a thin layer. Provided that proper techniques of preparation and administration are employed, the phospholipids tested are a promising surfactant substitute worthy of clinical study.

Surfactant and pulmonary blood flow distributions following treatment of premature lambs with natural surfactant.

“…After surfactant instillation, both premature animals and infants with RDS have prompt improvements in Pao2 values, compliance, and a temporary clearing of the chest x-ray (1)(2)(3)(4)(5)(6)(7)(8). Surfactant when administered to both prematurely delivered and adult animals can be found by histologic techniques in the alveoli (9,10). However, if surfactant suspensions distribute to the lung as do particles administered by either aerosol or by tracheal instillation, a nonhomogeneous distribution should occur (1 1).…”

Dynamic Surface Properties of Pulmonary Surfactant Proteins SP-B and SP-C and Their Mixtures with Dipalmitoylphosphatidylcholine

“…from films compressed beyond collapse points (Snik et al, 1978;Notter et al, 1980a,b;Keough et al, 1983). A large number of studies, concerned with preparation of substitutes of lung surfactant for replacement therapy, have been directed at the effects of additional pulmonary surfactant components, such as unsaturated phospholipids, phosphatidylglycerols, and cholesterol, on the adsorption rate (Obladen et al, 1979;Notter et al, 1983) and on the respreadability of DPPC (Notter et al, 1980a,b;Fontanges et al, 1984;Fleming et al, 1983; Fleming & Keough, 1988). The hydrophobic pulmonary surfactant-associated proteins, SP-B and SP-C, enhance the rate of adsorption of phospholipids from vesicles in the subphase into the air-water interface.…”

Lung Expansion in Premature Newborn Rabbits Treated with Emulsified Synthetic Surfactant; Principles for Experimental Evaluation of Synthetic Substitutes for Pulmonary Surfactant

“…Other li quid surfactant substitutes have been deve loped, or even patented [8] without convin cing documentation of their physiological activity in in vivo experiments. These in clude suspensions of DPPC + dipalmitoyIphosphatidylglycerol, 9:1, prepared as 'multilamellarliposomes' [28], DPPC + un saturated phosphatidylcholine + cholester ol, 3:03:1.65:1 [16], DPPC + dioleylphosphatidylcholine, 9:1 [27], DPPC + hexadecanol in proportions 9:2 [8], DPPC emulsified with fluorocarbon oil [21], and DPPC dissolved in ethanol [34], Morley et al [22] emphasized that it is difficult to obtain an effective preparation of surfactant phospholipids simply by sonicating the 'right' combination of lip ids in water, as this procedure results in a system of liposomes in water, from which surfactant molecules are donated only re luctantly to an air-liquid interface. These authors mean that the hydration of the po lar groups is the 'driving force' for spread ing of amphipathic lipids on an aqueous hypophase.…”