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Titolo:
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
Autore:
Szebeni, J; Fontana, JL; Wassef, NM; Mongan, PD; Morse, DS; Dobbins, DE; Stahl, GL; Bunger, R; Alving, CR;
Indirizzi:
Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Membrane Biochem, Walter Reed Army Med Ctr Washington DC USA 20307 , Dept Membrane Biochem, Uniformed4Serv Univ Hlth Sci, Dept Anesthesiol & Physiol, Bethesda, MD 2081 Uniformed Serv Univ Hlth Sci Bethesda MD USA 20814 iol, Bethesda, MD 2081 HarvardsUniv, Sch Med,Ctr Expt Therapeut & Reperfus Injury, Brigham & Women Harvard Univ Boston MA USA Therapeut & Reperfus Injury, Brigham & Women
Titolo Testata:
CIRCULATION
fascicolo: 17, volume: 99, anno: 1999,
pagine: 2302 - 2309
SICI:
0009-7322(19990504)99:17<2302:HCIBLA>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
MYOCARDIAL-ISCHEMIA; IN-VITRO; ACTIVATION; AMPHOTERICIN; DOXORUBICIN; COMPONENTS; MECHANISM; INFUSION; RELEASE; SYSTEM;
Keywords:
thromboxane; hemodynamics; hypertension, pulmonary; immune system; blood cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Szebeni, J Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Membrane Biochem, Walter Reed Army Med Ctr Washington DC USA 20307 rane Biochem,
Citazione:
J. Szebeni et al., "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", CIRCULATION, 99(17), 1999, pp. 2302-2309

Abstract

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 nod 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<0.01) alterations included 79+/-9% (mean+/-SEM) rise in pulmonary arterial pressure, 30+/-7% decline in cardiac output, 11+/-2% increase in heart rate, 236+/-54% increase in pulmonary vascular resistance, 71+/-27% increase insystemic vascular resistance, and up to a 100-fold increase in plasma thromboxane B-2. These changes peaked between and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose-dependent (ED50=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 antibudy (GS1), by sCR1 or by indomethacin. Liposomes caused C5a production in pig serum invitro through classic pathway activation and bound Ige 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).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/04/20 alle ore 00:39:49