Exchange transfusion with albumin-heme as an artificial O2-infusion into anesthetized rats: physiological responses, O2-delivery, and reduction of the oxidized hemin sites by red blood cells.
Human serum albumin (HSA) incorporating synthetic hemes, the tetrakis(o-pivalamido)phenylporphinatoiron(II) derivative (FeP), is an artificial hemoprotein (HSA-FeP) which is able to reversibly bind and release dioxygen under physiological conditions (in aqueous media, pH 7.4, 37 degrees C) like hemoglobin and myoglobin. Physiological responses to exchange transfusion with HSA-FeP solution [[HSA], 5 g/dL; FeP/HSA, 4 (mol/mol)] into rats after hemodilution and hemorrhage (Hct, about 10%) has been evaluated. The declined mean arterial pressure (MAP) and blood flow after a 70% exchange with HSA and the further 40% bleeding of blood were significantly recovered up to about 90% of the baseline values by the injection of HSA-FeP. Furthermore, the renal cortical O(2)-tensions and skeletal tissue O(2)-tensions were also increased, indicating the in vivo O(2)-delivery of HSA-FeP. Autoxidation of ferrous Fe(II)P to ferric Fe(III)P was retarded in the blood stream; the half-lifetime of the dioxygenated FeP [tau(1/2)(O(2))] in vivo was 4.1 h [cf. 1.0 h (in vitro)]. It has been found that autooxidized Fe(III)P was certainly reduced in the whole blood suspension. Physiological concentrations of ascorbic acid continuously provided by red blood cells probably rereduces Fe(III)P, leading to the apparent long lifetime of the dioxygenated species of FeP.
Tsuchida
E
E
Department of Polymer Chemistry, Advanced Research Institute for Science & Engineering, Waseda University, Tokyo 169-8555, Japan.
Komatsu
T
T
Hamamatsu
K
K
Matsukawa
Y
Y
Tajima
A
A
Yoshizu
A
A
Izumi
Y
Y
Kobayashi
K
K
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001665:Binding Sites; D001802:Blood Substitutes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005078:Exchange Transfusion, Whole Blood / Q000379:methods*; D005290:Ferric Compounds / Q000097:blood; D005296:Ferrous Compounds / Q000097:blood; D006207:Half-Life; D006420:Hemeproteins / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006427:Hemin / Q000378:metabolism*; D006438:Hemodilution; D006470:Hemorrhage / Q000628:therapy; D008297:Male; D010084:Oxidation-Reduction; D010100:Oxygen / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000075462:Serum Albumin, Human
D001802:Blood Substitutes; D005290:Ferric Compounds; D005296:Ferrous Compounds; D006420:Hemeproteins; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; C400056:rHSA-FeP protein, human; D006427:Hemin; D001205:Ascorbic Acid; D010100:Oxygen; D000075462:Serum Albumin, Human