Lyophilized plasma reconstituted with ascorbic acid suppresses inflammation and oxidative DNA damage

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

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    BACKGROUND: Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model. METHODS: Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2′-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage. RESULTS: No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24). CONCLUSIONS: Resuscitaiton with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.

    Original languageEnglish (US)
    Pages (from-to)20-25
    Number of pages6
    JournalJournal of Trauma - Injury, Infection and Critical Care
    Volume71
    Issue number1
    DOIs
    StatePublished - Jul 2011

    Fingerprint

    Ascorbic Acid
    DNA Damage
    Inflammation
    Hydrochloric Acid
    Citric Acid
    Hemorrhagic Shock
    Multiple Trauma
    Resuscitation
    Interleukin-6
    Cytokines
    Deoxyguanosine
    Blood Coagulation
    Swine
    Biomarkers
    Enzyme-Linked Immunosorbent Assay
    Acids
    Serum

    Keywords

    • Ascorbic acid
    • Inflammation
    • Lyophilized plasma
    • Oxidative DNA damage

    ASJC Scopus subject areas

    • Surgery
    • Critical Care and Intensive Care Medicine

    Cite this

    Lyophilized plasma reconstituted with ascorbic acid suppresses inflammation and oxidative DNA damage. / Van, Philbert; Hamilton, Gregory J.; Kremenevskiy, Igor V.; Sambasivan, Chitra; Spoerke, Nicholas J.; Differding, Jerome A.; Watters, Jennifer; Schreiber, Martin.

    In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 71, No. 1, 07.2011, p. 20-25.

    Research output: Contribution to journalArticle

    Van, Philbert ; Hamilton, Gregory J. ; Kremenevskiy, Igor V. ; Sambasivan, Chitra ; Spoerke, Nicholas J. ; Differding, Jerome A. ; Watters, Jennifer ; Schreiber, Martin. / Lyophilized plasma reconstituted with ascorbic acid suppresses inflammation and oxidative DNA damage. In: Journal of Trauma - Injury, Infection and Critical Care. 2011 ; Vol. 71, No. 1. pp. 20-25.
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    abstract = "BACKGROUND: Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model. METHODS: Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2′-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage. RESULTS: No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24). CONCLUSIONS: Resuscitaiton with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.",
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    author = "Philbert Van and Hamilton, {Gregory J.} and Kremenevskiy, {Igor V.} and Chitra Sambasivan and Spoerke, {Nicholas J.} and Differding, {Jerome A.} and Jennifer Watters and Martin Schreiber",
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    AU - Van, Philbert

    AU - Hamilton, Gregory J.

    AU - Kremenevskiy, Igor V.

    AU - Sambasivan, Chitra

    AU - Spoerke, Nicholas J.

    AU - Differding, Jerome A.

    AU - Watters, Jennifer

    AU - Schreiber, Martin

    PY - 2011/7

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    N2 - BACKGROUND: Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model. METHODS: Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2′-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage. RESULTS: No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24). CONCLUSIONS: Resuscitaiton with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.

    AB - BACKGROUND: Lyophilized plasma (LP) has been shown to be as effective as fresh frozen plasma (FFP) for resuscitation in polytrauma and hemorrhagic shock. LP reconstituted with ascorbic acid is associated with suppression of cytokines when compared with fresh frozen plasma. We aimed to determine the effect of using alternate LP reconstitution acids on physiologic parameters, blood loss, coagulation, oxidative DNA damage, and proinflammatory cytokines in a polytrauma and hemorrhagic shock model. METHODS: Thirty swine were anesthetized, subjected to polytrauma, hemorrhagic shock, and randomized to resuscitation with LP-ascorbic acid (AA), LP-citric acid (CA), or LP-hydrochloric acid (HCL). Physiologic data were continuously monitored, blood loss measured, and serum collected at baseline, 2 hours, and 4 hours for enzyme-linked immunosorbent assays. Measured 8-OH-2′-deoxyguanosine (8-OHdG) was a biomarker of oxidative DNA damage. RESULTS: No differences were observed in physiologic measures, blood loss, or coagulation parameters. Interleukin-6 increased over time for all groups, but at 2 hours, the concentration in AA (median [minimum, maximum]: 113 ng/mL [0, 244]) was lower compared with CA (181 ng/mL [69, 314], p = 0.01) and HCL (192 ng/mL [41, 310], p = 0.03). Comparing 4 hours to baseline, a significant increase in oxidative DNA damage was observed in CA (22.9 ng/mL [16.3, 34.3] vs. 15.6 ng/mL [13.6, 26.7], p = 0.03) and HCL (19.6 ng/mL [15.7, 56.7] vs. 15.8 ng/mL [11.6, 21.4], p = 0.01) but not in AA (17.9 ng/mL [12.6, 26.9] vs. 17.1 ng/mL [11.8, 18.4], p = 0.24). CONCLUSIONS: Resuscitaiton with AA results in decreased interleukin-6 expression and oxidative DNA damage compared with CA and HCL.

    KW - Ascorbic acid

    KW - Inflammation

    KW - Lyophilized plasma

    KW - Oxidative DNA damage

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