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Iron accelerates hemoglobin oxidation increasing mortality in vascular diseased guinea pigs following transfusion of stored blood
Jin Hyen Baek, … , Dominik J. Schaer, Paul W. Buehler
Jin Hyen Baek, … , Dominik J. Schaer, Paul W. Buehler
Published May 4, 2017
Citation Information: JCI Insight. 2017;2(9):e93577. https://doi.org/10.1172/jci.insight.93577.
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Research Article Hematology Vascular biology

Iron accelerates hemoglobin oxidation increasing mortality in vascular diseased guinea pigs following transfusion of stored blood

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Abstract

Non–transferrin-bound iron (NTBI) and free hemoglobin (Hb) accumulate in circulation following stored RBC transfusions. This study investigated transfusion, vascular disease, and mortality in guinea pigs after stored RBC transfusion alone and following cotransfusion with apo-transferrin (apo-Tf) and haptoglobin (Hp). The effects of RBC exchange transfusion dose (1, 3, and 9 units), storage period (14 days), and mortality were evaluated in guinea pigs with a vascular disease phenotype. Seven-day mortality and the interaction between iron and Hb as cocontributors to adverse outcome were studied. Concentrations of iron and free Hb were greatest after transfusion with 9 units of stored RBCs compared with fresh RBCs or stored RBCs at 1- and 3-unit volumes. Nine units of stored RBCs led to mortality in vascular diseased animals, but not normal animals. One and 3 units of stored RBCs did not cause a mortality effect, suggesting the concomitant relevance of NTBI and Hb on outcome. Cotransfusion with apo-Tf or Hp restored survival to 100% following 9-unit RBC transfusions in vascular diseased animals. Our data suggest that increases in plasma NTBI and Hb contribute to vascular disease–associated mortality through iron-enhanced Hb oxidation and enhanced tissue injury.

Authors

Jin Hyen Baek, Ayla Yalamanoglu, Yamei Gao, Ricardo Guenster, Donat R. Spahn, Dominik J. Schaer, Paul W. Buehler

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Figure 4

Free iron enhances the oxidation of free hemoglobin (Hb) and this biochemical reaction can be attenuated with increasing concentrations of apo-transferrin (apo-Tf).

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Free iron enhances the oxidation of free hemoglobin (Hb) and this bioche...
(A) The UV-visible spectral decay curves are shown for each of the Hb-iron-apo-Tf mixing groups. (B) An acceleration in autoxidation rates is observed between the following groups: Hb versus Hb/Fe (n = 3, P = 0.0001); Hb/Fe versus Hb/Fe/apo-TF (100 μM) (n = 3, P = 0.001); Hb/Fe/apo-TF (100 μM) versus Hb/Fe/apo-TF (50 μM) (n = 3, P = 0.0001); and Hb/Fe/apo-TF (50 μM) versus Hb/Fe/apo-TF (25 μM) (n = 3, P = 0.0001). All statistical comparisons were made using an ANOVA with a multiple comparisons test. All data are presented as individual values with the mean ± SD. (C) 4-Hydroxynonenal immunochemistry of thoracic aorta tissue sections showing brown/orange immunoreactivity on adventitia and media. Left: Original magnification, ×100. Scale bars: 50 μm. Right: Original magnification, ×400. Scale bars: 20 μm. (D) 4-Hydroxynonenal immunochemistry of non-necrotic renal cortical tissue sections showing brown/orange immunoreactivity in the renal tubules. Original magnification, ×600. Scale bars: 50 μm. All images were captured identically in high dynamic range (HDR) mode with default settings. Magnification = ocular lens (×10) × objective.
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