Lyophilized plasma with ascorbic acid decreases inflammation in hemorrhagic shock

Gregory J. Hamilton, Philbert Van, Jerome A. Differding, Igor V. Kremenevskiy, Nicholas J. Spoerke, Chitra Sambasivan, Jennifer Watters, Martin Schreiber

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Background: Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown. Methods: Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals. Results: No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p <0.05), but less so at 2 hours in the AA group compared with CA and HCl. Conclusion: In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.

    Original languageEnglish (US)
    Pages (from-to)292-298
    Number of pages7
    JournalJournal of Trauma - Injury, Infection and Critical Care
    Volume71
    Issue number2
    DOIs
    StatePublished - Aug 2011

    Fingerprint

    Hemorrhagic Shock
    Ascorbic Acid
    Inflammation
    Hydrochloric Acid
    Citric Acid
    Interleukin-6
    Resuscitation
    Enzyme-Linked Immunosorbent Assay
    Hemorrhage
    Cytokines
    Gene Expression
    Pseudogenes
    Mortality
    Wounds and Injuries
    Hypothermia
    Serum
    Interleukin-8
    Femur
    Swine
    Animal Models

    Keywords

    • Ascorbic acid
    • Hemorrhagic shock
    • Inflammation
    • Lyophilized plasma

    ASJC Scopus subject areas

    • Surgery
    • Critical Care and Intensive Care Medicine

    Cite this

    Lyophilized plasma with ascorbic acid decreases inflammation in hemorrhagic shock. / Hamilton, Gregory J.; Van, Philbert; Differding, Jerome A.; Kremenevskiy, Igor V.; Spoerke, Nicholas J.; Sambasivan, Chitra; Watters, Jennifer; Schreiber, Martin.

    In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 71, No. 2, 08.2011, p. 292-298.

    Research output: Contribution to journalArticle

    Hamilton, Gregory J. ; Van, Philbert ; Differding, Jerome A. ; Kremenevskiy, Igor V. ; Spoerke, Nicholas J. ; Sambasivan, Chitra ; Watters, Jennifer ; Schreiber, Martin. / Lyophilized plasma with ascorbic acid decreases inflammation in hemorrhagic shock. In: Journal of Trauma - Injury, Infection and Critical Care. 2011 ; Vol. 71, No. 2. pp. 292-298.
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    abstract = "Background: Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown. Methods: Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals. Results: No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p <0.05), but less so at 2 hours in the AA group compared with CA and HCl. Conclusion: In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.",
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    T1 - Lyophilized plasma with ascorbic acid decreases inflammation in hemorrhagic shock

    AU - Hamilton, Gregory J.

    AU - Van, Philbert

    AU - Differding, Jerome A.

    AU - Kremenevskiy, Igor V.

    AU - Spoerke, Nicholas J.

    AU - Sambasivan, Chitra

    AU - Watters, Jennifer

    AU - Schreiber, Martin

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    N2 - Background: Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown. Methods: Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals. Results: No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p <0.05), but less so at 2 hours in the AA group compared with CA and HCl. Conclusion: In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.

    AB - Background: Delivery of a high ratio of plasma to packed red blood cells to patients who require massive transfusion is associated with improved survival. Hemorrhagic shock causes increased production of pro-inflammatory cytokines. These are associated with late morbidity and mortality. The use of fresh frozen plasma makes high ratio resuscitation logistically difficult and does not address dysfunctional inflammation. Lyophilized plasma (LP) is a stable powdered form of plasma that is both safe and easily reconstituted. Previous work demonstrated that LP reconstituted with ascorbic acid (AA) decreased inflammation. Whether the reduction of inflammation was associated with LP or the AA is unknown. Methods: Thirty female swine were anesthetized and subjected to a multisystem combat relevant model consisting of femur fracture, controlled hemorrhage, and hypothermia. A standardized grade V liver injury was made and the animals were randomly assigned to receive LP reconstituted with AA, citric acid (CA), or hydrochloric acid (HCl). Blood was drawn at baseline and at 2 hours and 4 hours for interleukin (IL)-6, IL-8, and tumor necrosis factor-α serum concentrations measured by enzyme-linked immunosorbent assay. Lung tissue was harvested and processed for gene expression before euthanizing the animals. Results: No differences were observed in mortality, baseline cytokine serum concentration, or gene expression. Enzyme-linked immunosorbent assay demonstrated that IL-6 concentration increased over time for all groups (p <0.05), but less so at 2 hours in the AA group compared with CA and HCl. Conclusion: In this animal model of trauma, hemorrhage and resuscitation, AA decreases IL-6 expression relative to CA and HCl. These findings confirm previous work from our laboratory and suggest that AA is responsible for suppression of dysfunctional inflammation in this model.

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