Activation of complement by fluosol attributable to the pluronic detergent micelle structure

David A. Ingram, Mervyn B. Forman, John J. Murray

Research output: Contribution to journalArticle

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Abstract

Fluosol, a complex mixture of perfluorocarbons with a high oxygen-carrying capacity emulsified with the detergent pluronic F-68 and various lipids, recently was approved for adjuvant therapy to reduce myocardial ischemia during coronary angioplasty. Anaphylactoid reactions after Fluosol infusion through activation of the complement pathway have been reported in some patients. We examined the mechanism of complement activation by Fluosol. In vitro, incubation of both dog and human plasma with Fluosol for 1 h caused a significant reduction in total hemolytic complement levels (CH50). None of the individual components of Fluosol tested activated complement. A reduction in CH50 levels similar to that observed with Fluosol was obtained after incubation of dog or human plasma with the detergent pluronic F-68 in combination with either perfluorocarbon. In vivo, a bolus injection of the detergent and perfluorocarbon fully mimicked the anaphylactoid reaction of Fluosol previously observed in dogs, with transient profound hypotension, tachycardia, and reduction in CH50 levels occurring ≤ 5 min. To investigate further the mechanism by which the pluronic/perfluorocarbon combination activates complement, an inert dense liquid (mineral oil or silicon oil) substituted for the perfluorocarbons produced comparable complement activation both in vitro and in vivo. These observations suggest that creation of a larger pluronic micelle around a core of perfluorocarbons or any inert dense substance, causes formation of a specific surface configuration, resulting in activation of the complement cascade.

Original languageEnglish (US)
Pages (from-to)456-461
Number of pages6
JournalJournal of cardiovascular pharmacology
Volume22
Issue number3
DOIs
StatePublished - Sep 1993

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Keywords

  • Complement
  • Fluosol
  • Micelle
  • Perfluorocarbons
  • Pluronic
  • Reperfusion injury

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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