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Activation of complement by Fluosol attributable to the pluronic detergent micelle structure
D A Ingram1, M B Forman, J J Murray
1Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0111.
Journal of Cardiovascular Pharmacology
|September 1, 1993
Summary
Fluosol, used to treat myocardial ischemia, can cause anaphylactoid reactions by activating the complement pathway. The detergent pluronic F-68 combined with perfluorocarbons or other inert substances forms micelles that trigger this complement cascade.
Area of Science:
- Biochemistry
- Immunology
- Cardiovascular Research
Background:
- Fluosol, a perfluorocarbon emulsion, is an approved adjuvant therapy for myocardial ischemia during coronary angioplasty.
- Anaphylactoid reactions have been reported following Fluosol infusion, potentially linked to complement pathway activation.
Purpose of the Study:
- To investigate the mechanism of complement activation induced by Fluosol.
- To identify the specific components and conditions responsible for Fluosol-mediated anaphylactoid reactions.
Main Methods:
- In vitro studies involved incubating dog and human plasma with Fluosol and its components, followed by measurement of total hemolytic complement (CH50) levels.
- In vivo studies in dogs involved bolus injections of Fluosol components to observe physiological responses and CH50 levels.
- Experiments substituted perfluorocarbons with inert dense liquids to further elucidate the role of micelle formation.
Main Results:
- Fluosol significantly reduced CH50 levels in both dog and human plasma in vitro.
- Neither perfluorocarbons nor pluronic F-68 alone activated complement; however, their combination mimicked Fluosol's effect.
- In vivo, the pluronic F-68/perfluorocarbon combination replicated Fluosol's anaphylactoid reactions, including hypotension and tachycardia.
- Inert dense liquids, when emulsified with pluronic F-68, also induced complement activation, suggesting micelle structure is key.
Conclusions:
- The anaphylactoid reactions associated with Fluosol are primarily caused by the formation of pluronic F-68 micelles around a core substance.
- This specific micelle surface configuration activates the complement cascade, leading to adverse reactions.
- The findings suggest that the physical structure of the emulsion, rather than the chemical nature of the core substance, is responsible for complement activation.