Inhaled Nitric Oxide Improves Outcomes in Mice Resuscitated With Stored Blood

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    ScienceDaily (Nov. 21, 2012) — Inhaled nitric oxide reduced the
    adverse effects of transfusing stored blood in mice, according to
    a study from the December issue of Anesthesiology. Researchers
    found that inhaled nitric oxide reduced tissue injury and im-
    proved short-term survival in mice that were resuscitated with a
    stored blood transfusion after hemorrhagic shock.

    An estimated 40 percent of critically ill individuals receive
    at least one unit of packed red blood cells in the intensive care
    unit. At Massachusetts General Hospital, the average human red
    cell storage duration is 16 days, and many units are stored for
    much longer, up to 42 days.

    Transfusion of blood stored for longer durations is associated
    with increased morbidity and mortality, especially in patients
    with cardiovascular disease. Stored blood cells have reduced
    ability to transport oxygen, and many are destroyed after trans-
    fusion causing vascular nitric oxide, an important cellular mes-
    senger, to be scavenged.

    "While blood transfusions help many patients, when red cells are stored for
    long periods before transfusion they can make some patients sicker," said study
    senior author Warren M. Zapol, M.D. "Our research was modeled in mice to repro-
    duce the adverse effects of stored blood transfusion and to learn which recipi-
    ents might be more sensitive."

    About the Study

    Mice were fed either a standard diet (10% calories from fat) or high-fat diet
    (60% calories from fat) for four to six weeks. They were then subjected to 90
    minutes of hemorrhagic shock, followed by resuscitation and transfusion with
    either fresh blood (less than 24 hours old) or blood stored for two weeks. There
    was no immune response to transfusion because the mice were transfused with
    genetically-identical mouse blood.

    Findings showed mice fed a standard diet, who received stored blood transfu-
    sion had increased tissue injury compared to those that received fresh blood
    transfusion. In addition, mice fed a high-fat diet that received stored blood
    transfusion had higher blood lactate levels and insufficient oxygen delivered
    via the blood stream, associated with a greater short-term mortality.

    Researchers found that when mice breathed nitric oxide, during and after
    transfusion, they had reduced tissue injury, lower lactate levels, and less in-
    flammation and oxidative stress. Inhaled nitric oxide also improved the short-
    term survival rate of mice fed a high-fat diet, who were resuscitated with
    stored blood transfusion.

    "Resuscitation with stored blood transfusion adversely impacts the outcomes of
    mice with hemorrhagic shock, an effect that is exacerbated by feeding mice a
    high-fat diet," continued Dr. Zapol. "Our research also confirms that stored
    blood transfusion is bad for mice that have diabetes or are overweight, and the
    toxicity of stored blood in mice can be prevented with inhaled nitric oxide."

    Stored blood administration remains a critical component of the treatment of
    hemorrhage or anemia which results in inadequate oxygen delivery to tissues.

    Dr. Zapol and his team hope their findings will help to better identify those
    patients who will be most susceptible to negative outcomes after a stored blood
    transfusion, as well as highlight the benefits of breathing nitric oxide when
    patients are transfused with stored red cells.
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