Human hemoglobin conjugated to carboxylate dextran as a potential red blood cell substitute. II--Pharmacotoxicological evaluation.
A solution of human hemoglobin bound to benzene tetracarboxylate substituted dextran, whose physicochemical characteristics are defined in part I, was evaluated in vivo as a potential red blood cell substitute. Further experiments show: - the confirmation of a lack of acute toxicity in mice and guinea pigs after injection of 12.5%, 25% and 50% of the blood mass and the absence of death in rabbits having undergone three successive 25% hemorrhagic shocks in three week intervals. A plasma half-life of 9.5 +/- 0.5 hours in 70-75% hemorrhagic shocks on guinea pigs and the absence of dex-BTC-Hb in thoracic and abdominal cavities. No tissue oedema was noticed. Total hemoglobinuria did not exceed 10% of the injected hemoglobin quantity and only involved free hemoglobin. A lack of death in 70-75% hemorrhagic shocks and survival times ranging from 10 hours to 3 days in total exchange transfusions in guinea pig experiments.
Menu
P
P
Faculté de Pharmacie, Nancy, France.
Faivre
B
B
Labrude
P
P
Riffard
P
P
Grandgeorge
M
M
Vigneron
C
C
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology* / Q000633:toxicity; D001810:Blood Volume; D003911:Dextrans / Q000494:pharmacology* / Q000633:toxicity; D005078:Exchange Transfusion, Whole Blood; D006168:Guinea Pigs; D006454:Hemoglobins / Q000494:pharmacology* / Q000633:toxicity; D006456:Hemoglobinuria / Q000209:etiology; D006801:Humans; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D012449:Safety; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy
D001802:Blood Substitutes; D003911:Dextrans; D006454:Hemoglobins; C040953:dextran-hemoglobin complex (deoxygenated); D010100:Oxygen