Search

In vitro cellular effects of perfluorochemicals correlate with their lipid solubility. Am J Physiol Lung Cell Mol Physiol 278: L1018-L1024, 2000.--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. perfluorocarbon; perflubron; membrane partitioning

Perflubron attenuates neutrophil adhesion to activated endothelial cells in vitro. Am J Physiol Lung Cell Mol Physiol 278: L1008-L1017, 2000.--Infiltration of activated neutrophils into the lung appears to be a key element in the severe lung injury that develops in animal models of acute lung injury. Partial liquid ventilation with perflubron has been shown to ameliorate tissue damage compared with conventional mechanical ventilation in acute lung injury models. Pilot experiments indicated that indirect exposure to perflubron could modulate the degree to which subsequent neutrophil binding to endothelial cell monolayers was upregulated after lipopolysaccharide activation. Endothelial cell monolayers preexposed to perflubron showed [is greater than] 40% reductions in the surface steady-state levels of E-selectin and intercellular adhesion molecule-1 achieved after proinflammatory activation (P [is less than] 0.05), which correlated with a reduction in the real-time association constants measured by biosensor techniques. These results indicate that direct contact with the perflubron liquid phase is not necessary to attenuate inflammatory responses. Rather, diffusion of perflubron from the alveolar space into the adjacent pulmonary vascular endothelial layer may modulate neutrophil adhesion and thereby reduce the rate of infiltration of activated neutrophils into the injured lung. acute lung injury; partial liquid ventilation; neutrophil infiltration; intercellular adhesion molecule-1; E-selectin