A single intravenous injection of 4 to 8 mg/kg of large, multilamellar, cholesterol-enriched lipid vesicles (containing 71% cholesterol; HC-MLV) induced marked bradycardia, arrhythmia, and transient decrease in systemic blood pressure in rats. A single higher dose (15-20 mg/kg), or repeated injections of 4 to 8 mg/kg HC-MLV, resulted in severe pulmonary hemorrhage and edema (ARDS-like histologic changes), systemic microthrombus formation, hemorrhage in the kidneys and liver, as well as early signs of diffuse myocardial damage. Complement depletion with cobra venom factor, or the use of thromboxane A2 receptor inhibitor (SQ30741), prevented these adverse reactions, pointing to the involvement of C activation and TXA2 release in the pathomechanism. The likely role of C activation was supported by the demonstration of strong C activation by HC-MLV in rat serum in vitro, along with the binding of natural IgG and IgM antibodies to these vesicles. The C activation by HC-MLV seems to proceed by way of the classic pathway mediated by natural antilipid antibodies. These studies present a novel, powerful method for inducing anaphylactoid shock and other C activation-related pathologic changes providing a model for multiple organ failure, semicrystalline cholesterol embolism, and C activation-related pseudoallergy.
|Number of pages||11|
|Journal||Journal of Applied Research|
|Publication status||Published - jún. 1 2003|
ASJC Scopus subject areas
- Pharmacology (medical)