{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:25:42Z","timestamp":1793453142730,"version":"4.5.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,5,4]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Intravenous 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.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Anesthetized 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 (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01) alterations included 79\u00b19% (mean\u00b1SEM) rise in pulmonary arterial pressure, 30\u00b17% decline in cardiac output, 11\u00b12% increase in heart rate, 236\u00b154% increase in pulmonary vascular resistance, 71\u00b127% increase in systemic vascular resistance, and up to a 100-fold increase in plasma thromboxane B\n            <jats:sub>2<\/jats:sub>\n            . These changes peaked between 1 and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose\u2013dependent (ED\n            <jats:sub>50<\/jats:sub>\n            =4.5\u00b11.4 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\n            <jats:sub>2<\/jats:sub>\n            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.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The 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 \u201ccomplement activation\u2013related pseudoallergy\u201d (CARPA).\n          <\/jats:p>","DOI":"10.1161\/01.cir.99.17.2302","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"2302-2309","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":166,"title":["Hemodynamic Changes Induced by Liposomes and Liposome-Encapsulated Hemoglobin in Pigs"],"prefix":"10.1161","volume":"99","author":[{"given":"Janos","family":"Szebeni","sequence":"first","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Fontana","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabila M.","family":"Wassef","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Mongan","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Morse","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Dobbins","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory L.","family":"Stahl","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Bu\u0308nger","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl R.","family":"Alving","sequence":"additional","affiliation":[{"name":"From the Departments of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC (J.S., N.M.W., C.R.A.); Anesthesiology and Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.L.F., P.D.M., D.E.D., R.B.); and Anesthesia, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Mass (D.S.M., G.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","unstructured":"Allen TM. 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