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

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 1

Vascular remodeling and endothelial dysfunction are increased in guinea pigs on a high-fat and high-sucrose diet (HFSD) compared with normal diet (ND) animals.

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Vascular remodeling and endothelial dysfunction are increased in guinea ...
(A) Light microscopy images of representative aorta sections from guinea pigs after 3 months on either ND or HFSD shown in the upper panel were stained with Masson’s trichrome (collagen = blue); sections in the lower panel were stained with the Verhoeff’s Van Giesen method (elastin fibers = black/brown; collagen fibers = red). Images were obtained at ×100 magnification and show increased visualization of collagen staining and elastin fragmentation in the vascular media. Scale bars: 100 μm. (B) Percentage area of collagen-positive staining was increased in aortas after 3 months on HFSD (filled circles) compared with ND (open circles) (n = 10, P = 0.0001 by a 2-tailed t test). (C) Collagen/elastin ratios were significantly increased in ND compared with HFSD (n = 10, P = 0.0001 by a 2-tailed t test); both are indicative of remodeling in elastic arteries. Both (D) systolic blood pressure and (E) pulse pressure significantly increased in HFSD (filled circles) compared with ND (open circles) guinea pigs (n = 12, P = 0.0001 (systolic blood pressure) by a 2-tailed t test) and (n = 12, P = 0.0001 (pulse pressure) by a 2-tailed t test). (F) Systemic vascular responsiveness (mean arterial blood pressure) in response to acetylcholine doses was significantly lower in HFSD (n = 12, closed circles) compared with ND guinea pigs (n = 12, open circles), suggesting significantly reduced endothelial NO availability. ND and HFSD guinea pig mean arterial pressure responses following an ANOVA with a multiple comparisons test demonstrated significant differences between groups †(0, 2.5, 5.0, and 10 μg): P = 0.9999 (0 μg), P = 0.0001 (2.5 μg), P = 0.0001 (5.0 μg), P = 0.0001 (10 μg). *P = 0.0001 compared with baseline. All data are presented as individual values with the mean ± SD. Magnification = ocular lens (×10) × objective.