Acute 40 percent exchange-transfusion with hemoglobin-vesicles (HbV) suspended in recombinant human serum albumin solution: degradation of HbV and erythropoiesis in a rat spleen for 2 weeks.
BACKGROUND
Hemoglobin-vesicles (HbVs; diameter, 251 +/- 81 nm) are artificial O(2) carriers. Their efficacy for acute exchange transfusion has been characterized in animal models. However subsequent profiles of recovery involving the degradation of HbV in the reticuloendothelial system (RES) and hematopoiesis remain unknown.


METHODS
Isovolemic 40 percent exchange transfusion was performed in 60 male Wistar rats with HbV suspended in 5 g per dL recombinant human serum albumin (rHSA; HbV/rHSA, [Hb] = 8.6 g/dL), stored rat RBCs suspended in rHSA (sRBC/rHSA), or rHSA alone. Hematological and plasma biochemical analyses and histopathological examination focusing on the spleen were conducted for the subsequent 14 days.


RESULTS
The reduced hematocrit (Hct) level (26%) for the HbV/rHSA and rHSA groups returned to its original level (43%) in 7 days. Plasma erythropoietin was elevated in all groups: the rHSA group showed the highest value on Day 1 (321 +/- 123 mIU/mL) relating to the anemic conditions (HbV/rHSA, 153 +/- 22; sRBC/rHSA, 63 +/- 7; baseline, 21 +/- 3). Simultaneously, splenomegaly occurred in all the groups as HbV/rHSA > rHSA > sRBC/rHSA. Histopathologically, the accumulated HbV in the spleen was undetectable by Day 14, but hemosiderin was deposited in slight quantities for both the HbV/rHSA and sRBC/rHSA groups. Considerable amounts of erythroblasts were apparent in the spleens of both the rHSA and the HbV/rHSA groups.


CONCLUSIONS
HbVs were phagocytized and degraded in RES, a physiological compartment for the degradation of RBCs, and the elevated erythropoietic activity resulted in the complete recovery of Hct within 7 days in the rat model.
Advanced Research Institute for Science and Engineering, Waseda University, Tokyo, Japan.
Hiromi
H
Sakai
Hirohisa
H
Horinouchi
Manabu
M
Yamamoto
Eiji
E
Ikeda
Shinji
S
Takeoka
Masuhiko
M
Takaori
Eishun
E
Tsuchida
Koichi
K
Kobayashi
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004900:Erythroblasts / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects*; D005078:Exchange Transfusion, Whole Blood; D006400:Hematocrit; D006454:Hemoglobins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D012157:Mononuclear Phagocyte System / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000008:administration & dosage / Q000737:chemistry*; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D001802:Blood Substitutes; D006454:Hemoglobins; D012709:Serum Albumin