Attenuation of myocardial reperfusion injury by perfluorochemical emulsions

Perfluorochemicals are substances with a small particle size, low viscosity, and high oxygen-carrying capacity. We have investigated the role of one perfluorochemical, Fluosol, an emulsion of two perfluorocarbons, a detergent [Pluronic F-68], and phospholipids on myocardial reperfusion injury in the closed-chest canine model. Intracoronary and intravenous Fluosol infused in the peri-reperfusion period significantly reduced infarct size and improved ventricular function up to two weeks after reperfusion. Fluosol attenuates neutrophil infiltration into the reperfused bed, preserves endothelial cell structure, and reduces neutrophil plugging of capillaries. Endothelium-dependent relaxation of large and small vessels was maintained 1 hour after reperfusion in Fluosol animals. Ex vivo studies showed apparent suppression of neutrophil chemotaxis and lysozyme degranulation. Unstimulated neutrophils manifested enhanced superoxide anion production within 5 minutes of incubation even with low concentrations of Fluosol, and this effect was almost entirely due to Pluronic F-68. Neutrophil stimulation was prevented by cytochalasin B, an inhibitor of phagocytosis. Perfluorochemicals may offer a novel therapy to enhance myocardial salvage after successful reperfusion. The mechanism appears to be due to “deactivation” of neutrophils peripherally, thereby reducing their cytotoxic potential in the reperfused myocardium.