In vitro cellular effects of perfluorochemicals correlate with their lipid solubility.
Preclinical studies comparing perflubron partial liquid ventilation with conventional mechanical ventilation have indicated that perflubron partial liquid ventilation may exert some anti-inflammatory effects. To assess whether these effects were related to the lipid solubility properties of perflubron rather than to nonspecific biophysical properties of the perfluorocarbon (PFC) liquid phase, we studied the effects of PFCs with varying lipid solubilities on the platelet aggregation response to various procoagulants and the erythrocyte hemolytic response to osmotic stress. In both cases, the degree of the response was directly related to the lipid solubility of the PFC. All the perflubron content of erythrocytes was found to be associated with the membrane compartment. The time to reach a maximum effect on hemolysis with perflubron was relatively slow (2-4 h), which paralleled the time for perflubron to accumulate in erythrocyte membranes. The rate and extent of perflubron partitioning into lecithin liposomes were similar to those of erythrocyte membranes, supporting the hypothesis that perflubron was partitioning into the lipid component of the membranes. Thus some of the potential modulatory effects of perflubron on excessive inflammatory responses that occur during acute lung injury and acute respiratory distress syndrome may be influenced in part by the extent of PFC partitioning into the lipid bilayers of cellular membranes.
Obraztsov
V V
VV
Department of Biological Research, Alliance Pharmaceutical Corporation, San Diego, California 92121, USA.
Neslund
G G
GG
Kornbrust
E S
ES
Flaim
S F
SF
Woods
C M
CM
D000818:Animals; D001802:Blood Substitutes / Q000493:pharmacokinetics; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005466:Fluorocarbons / Q000493:pharmacokinetics*; D006461:Hemolysis; D006801:Humans; D006842:Hydrocarbons, Brominated; D007038:Hypotonic Solutions / Q000494:pharmacology; D050356:Lipid Metabolism; D008081:Liposomes / Q000378:metabolism; D000069463:Olive Oil; D010713:Phosphatidylcholines; D010938:Plant Oils; D010974:Platelet Aggregation / Q000187:drug effects; D012044:Regression Analysis; D012995:Solubility; D013552:Swine
D001802:Blood Substitutes; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D007038:Hypotonic Solutions; D008081:Liposomes; D000069463:Olive Oil; D010713:Phosphatidylcholines; D010938:Plant Oils; C008807:perfluorotributylamine; C057576:bis(perfluorobutyl)ethene; C003072:perflubron