The use of perfluorocarbons (PFCs) in medicine has seen its share of false starts and abandoned investigations. As a result of the many unusual events that occur when introducing a chemically inert compound into biological systems, unexpected events have led to detours in their medical development.
Studies of PFCs to support pulmonary gas exchange were initially embraced with enthusiasm and seemed to offer hope as a treatment for acute hypoxic respiratory failure resulting from many causes. Perhaps due to an insufficient understanding of the biologic effects of PFCs, early human trials, which focused primarily on gas exchange and clinical outcomes, were unsuccessful and led to a premature loss of interest in PFCs by clinicians and funding agencies. Furthermore, the practical challenges of performing either tidal/total liquid ventilation (TLV) or partial liquid ventilation (PLV) in fragile, critically ill patients made the early optimism for a revolution in the care of acute lung injury fade quickly. Attempts to reproduce the early laboratory successes in humans were disappointing and point out the inadequacy of our animals models in recreating established human disease. Unfortunately, the initial clinical trials were not designed to study in vivo biological processes in humans nor were they designed to determine why liquid ventilation failed as it was applied in the clinical setting. Nonetheless, ongoing laboratory investigations have continued to suggest very real effects on many different tissues in which PFCs have been investigated, e.g., erythrocytes, leukocytes, immune cells, lung, liver, type-II cells, intestine, pancreas, heart.
The lack of intrinsic metabolic pathways to effectively process PFCs has led to the assumption that all of the effects seen in vivo and in vitro are based upon physical, chemical, and mechanical properties of the various PFC compounds, e.g, density, viscosity, vapor pressure, hydrophobicity, lipophilicity. It is unlikely, however, that the effects on inflammation seen in the lung result solely from the physical presence of PFCs in the alveolar space. Thus, other mechanisms must underlie the responses seen in a wide variety of cell types, tissues, and experimental situations. These mechanisms can be grossly categorized as (1) physical barriers created by the presence of PFCs, (2) modifiers of biological membranes, (3) non-covalent interactions with proteins, and (4) solvents for lipid biological mediators.
A growing body of literature demonstrates a wide range of intriguing possibilities for the use of PFCs in biological systems. Exposure of cells and intact animals to PFCs continues to receive attention, but a much more exciting possibility is seen in the use of respiratory gas saturated with PFC vapor. Furthermore, mixtures of different PFCs and PFC emulsions continue to reveal unexpected results in basic research. These findings raise additional important opportunities for research and the development of new applications in medicine