ACTIVATION OF COMPLEMENT BY FLUOSOL ATTRIBUTABLE TO THE PLURONIC DETERGENT MICELLE STRUCTURE

Fluosol, a complex mixture of perfluorocarbons with a high oxygen-carr ying capacity emulsified with the detergent pluronic F-68 and various lipids, recently was approved for adjuvant therapy to reduce myocardia l ischemia during coronary angioplasty. Anaphylactoid reactions after Fluosol infusion through activation of the complement pathway have bee n reported in some patients. We examined the mechanism of complement a ctivation by Fluosol. In vitro, incubation of both dog and human plasm a with Fluosol for 1 h caused a significant reduction in total hemolyt ic complement levels (CH50). None of the individual components of Fluo sol tested activated complement. A reduction in CH-50 levels similar t o that observed with Fluosol was obtained after incubation of dog or h uman plasma with the detergent pluronic F-68 in combination with eithe r perfluorocarbon. In vivo, a bolus injection of the detergent and per fluorocarbon fully mimicked the anaphylactoid reaction of Fluosol prev iously observed in dogs, with transient profound hypotension, tachycar dia, and reduction in CH50 levels occurring less-than-or-equal-to 5 mi n. To investigate further the mechanism by which the pluronic/perfluor ocarbon combination activates complement, an inert dense liquid (miner al oil or silicon oil) substituted for the perfluorocarbons produced c omparable complement activation both in vitro and in vivo. These obser vations suggest that creation of a larger pluronic micelle around a co re of perfluorocarbons or any inert dense substance, causes formation of a specific surface configuration, resulting in activation of the co mplement cascade.