Cerebrovascular involvement in liposome-induced cardiopulmonary distress in pigs.
Intravenous administration of liposomes, including Doxil, can cause severe life-threatening hemodynamic changes in pigs. The reaction is due to complement activation, and it is characterized by massive pulmonary hypertension, systemic hypotension, and severe cardiac abnormalities including falling cardiac output, tachy-or bradycardia with arrhythmia. There were no data suggesting the involvement of cerebrovascular changes in this reaction; however, clinical observations allowed this hypothesis. Here we measured the accompanying changes during liposome infusion by monitoring pulsatile electrical impedance (rheoencephalogram- REG) on the skull (n=24 pigs, 57 trials, 19 types of liposomes). A transient but significant decrease of REG pulse amplitudes followed the injection of liposomes (78.43% in the total sample, and 91.66% in the Doxil subgroup; P=0.003, n=12), indicating the involvement of cerebrovascular reaction during liposome infusion.
Bodo
Michael
M
Department of Resuscitative Medicine, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. michael.bodo@us.army.mil
Szebeni
Janos
J
Baranyi
Lajos
L
Savay
Sandor
S
Pearce
Frederick J
FJ
Alving
Carl R
CR
Bünger
Rolf
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004562:Electrocardiography; D004569:Electroencephalography / Q000379:methods; D006439:Hemodynamics; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects*; D012212:Rheology / Q000379:methods; D013552:Swine
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin