INFLUENCE OF PERFLUBRON EMULSION PARTICLE-SIZE ON BLOOD HALF-LIFE ANDFEBRILE RESPONSE IN RATS

Perfluorochemical (PFC) emulsions are particulate in nature and, as su ch, can cause delayed febrile reactions when injected intravenously. T his study investigated the influence of emulsion particle size on intr avascular retention and on body temperature changes in unrestrained co nscious rats. Concentrated (60% to 90% w/v) emulsions based on perflub ron (perfluorooctyl bromide [PFOB]) with mean particle sizes ranging f rom 0.05 mu m to 0.63 mu m were tested. Rats were fitted with a chroni c jugular catheter and an abdominal body temperature telemetry unit. F ully recovered, conscious rats were monitored for 24 hours after infus ion (dose = 2.7 g PFC/kg). Emulsion blood half-life (T-1/2) was determ ined from blood perflubron levels measured by gas chromatography. Emul sions with a particle size of 0.2-0.3 mu m caused fevers (6 to 8 hour duration) which peaked at 1-1.5 degrees C above normal (similar to 37. 5 degrees C). Fevers could be blocked by i.v. treatment with either cy clooxygenase inhibitors (ibuprofen) or corticosteroids (dexamethasone) . Both intensity and duration of the temperature response, quantified by area under the temperature curve, was decreased significantly for e mulsions with a particle size less than or equal to 0.12 mu m. Blood T -1/2 varied inversely with particle size, and was 3 to 4 fold longer f or emulsions with a mean particle size less than or equal to 0.2 mu m. Thus, smaller emulsion particles more effectively evaded the reticulo endothelial system, which resulted in longer intravascular retention, less macrophage activity, and reduced febrile responses.