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Diabetes augments and inhaled nitric oxide prevents the adverse hemodynamic effects of transfusing syngeneic stored blood in mice

Authors

  • Binglan Yu,

    1. From the Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
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  • Chong Lei,

    1. From the Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
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  • David M. Baron,

    1. From the Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
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  • Andrea U. Steinbicker,

    1. From the Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
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    • Present address: Department of Anesthesiology and Intensive Care Medicine, University Hospital Muenster, Muenster, Germany.

  • Kenneth D. Bloch,

    1. From the Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
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  • Warren M. Zapol

    Corresponding author
    1. From the Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
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  • This work was supported by Eleanor and Miles Shore 50th Anniversary Fellowship (217249) to BY at Harvard Medical School and by grants from the National Natural Science Foundation of China to CL (81000232) and from the NHLBI (R01 DK082971) to KDB.

Warren M. Zapol, MD, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Thier #503, Boston, MA 02114; e-mail: wzapol@partners.org.

Abstract

BACKGROUND: Stored red blood cells (RBCs) undergo progressive deleterious functional, biochemical, and structural changes. The mechanisms responsible for the adverse effects of transfusing stored RBCs remain incompletely elucidated.

STUDY DESIGN AND METHODS: Awake wild-type (WT) mice, WT mice fed a high-fat diet (HFD-fed WT) for 4 to 6 weeks, and diabetic (db/db) mice were transfused with syngeneic leukoreduced RBCs or supernatant with or without oxidation (10% of total blood volume) after storage for not more than 24 hours (FRBCs) or 2 weeks (SRBCs). Inhaled nitric oxide (NO) at 80 parts per million was administered to a group of mice transfused with SRBCs. Blood and tissue samples were collected 2 hours after transfusion to measure iron and cytokine levels.

RESULTS: SRBCs had altered RBC morphology and a reduced P50. Transfusion of SRBCs into WT or HFD-fed WT mice did not produce systemic hemodynamic changes. In contrast, transfusion of SRBCs or supernatant from SRBCs into db/db mice induced systemic hypertension that was prevented by concurrent inhalation of NO. Infusion of washed SRBCs or oxidized SRBC supernatant into db/db mice did not induce hypertension. Two hours after SRBC transfusion, plasma hemoglobin (Hb), interleukin-6, and serum iron levels were increased.

CONCLUSION: Transfusion of syngeneic SRBCs or the supernatant from SRBCs produces systemic hypertension and vasoconstriction in db/db mice. It is likely that RBC storage, by causing in vitro hemolysis and posttransfusion hemoglobinemia, produces sustained NO scavenging and vasoconstriction in mice with endothelial dysfunction. Vasoconstriction is prevented by oxidizing the supernatant of SRBCs or breathing NO during SRBC transfusion.

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