Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5a antibody
| Autor: | Janos Szebeni, John L. Fontana, Paul D. Mongan, Nabila M. Wassef, Gregory L. Stahl, Rolf Bünger, Carl R. Alving, David Morse, Dobbins De |
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| Rok vydání: | 1999 |
| Předmět: |
Pulmonary Circulation
Thromboxane Swine Indomethacin Complement C5a Pharmacology Thromboxane A2 chemistry.chemical_compound Hemoglobins Physiology (medical) Hypersensitivity Medicine Animals Humans Complement Activation Liposome Respiratory Distress Syndrome Newborn business.industry Pseudoallergy Zymosan Hemodynamics Infant Newborn Complement System Proteins medicine.disease Pulmonary hypertension Thromboxane B2 medicine.anatomical_structure chemistry Immunology Liposomes Vascular resistance Female Receptors Complement 3d Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 99(17) |
| ISSN: | 1524-4539 |
| Popis: | Background —Intravenous administration of some liposomal drugs can trigger immediate hypersensitivity reactions that include symptoms of cardiopulmonary distress. The mechanism underlying the cardiovascular changes has not been clarified. Methods and Results —Anesthetized pigs (n=18) were injected intravenously with 5-mg boluses of large multilamellar liposomes, and the ensuing hemodynamic, hematologic, and laboratory changes were recorded. The significant ( P 2 . These changes peaked between 1 and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose–dependent (ED 50 =4.5±1.4 mg), and were quantitatively reproducible in the same animal several times over 7 hours. The liposome-induced rises of pulmonary arterial pressure showed close quantitative and temporal correlation with elevations of plasma thromboxane B 2 and were inhibited by an anti-C5a monoclonal antibody (GS1), by sCR1, or by indomethacin. Liposomes caused C5a production in pig serum in vitro through classic pathway activation and bound IgG and IgM natural antibodies. Zymosan- and hemoglobin-containing liposomes and empty liposomes caused essentially identical pulmonary changes. Conclusions —The intense, nontachyphylactic, highly reproducible, complement-mediated pulmonary hypertensive effect of minute amounts of intravenous liposomes in pigs represents a unique, unexplored phenomenon in circulation physiology. The model provides highly sensitive detection and study of cardiopulmonary side effects of liposomal drugs and many other pharmaceutical products due to “complement activation–related pseudoallergy” (CARPA). |
| Databáze: | OpenAIRE |
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