The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock

Michael Gröger, Martin Wepler, Ulrich Wachter, Tamara Merz, Oscar McCook, Sandra Kress, Britta Lukaschewski, Sebastian Hafner, Markus Huber-Lang, Enrico Calzia, Michael Georgieff, Noriyuki Nagahara, Csaba Szabo, Peter Radermacher, Clair Hartmann

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    Abstract

    INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock. METHODS: Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption. RESULTS: 3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma. CONCLUSIONS: In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.

    Original languageEnglish (US)
    Pages (from-to)472-478
    Number of pages7
    JournalShock (Augusta, Ga.)
    Volume51
    Issue number4
    DOIs
    StatePublished - Apr 1 2019

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    Traumatic Shock
    Hemorrhagic Shock
    Mutation
    Wounds and Injuries
    Thorax
    Acute Lung Injury
    Hemodynamics
    Oxygen Consumption
    Gases
    Kidney
    Lung
    Hydrogen Sulfide
    Acids
    Mortality
    Mitochondrial Proteins
    Critical Care
    3-mercaptopyruvic acid
    Mechanics
    Artificial Respiration
    Resuscitation

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

    Cite this

    Gröger, M., Wepler, M., Wachter, U., Merz, T., McCook, O., Kress, S., ... Hartmann, C. (2019). The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock. Shock (Augusta, Ga.), 51(4), 472-478. https://doi.org/10.1097/SHK.0000000000001165

    The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock. / Gröger, Michael; Wepler, Martin; Wachter, Ulrich; Merz, Tamara; McCook, Oscar; Kress, Sandra; Lukaschewski, Britta; Hafner, Sebastian; Huber-Lang, Markus; Calzia, Enrico; Georgieff, Michael; Nagahara, Noriyuki; Szabo, Csaba; Radermacher, Peter; Hartmann, Clair.

    In: Shock (Augusta, Ga.), Vol. 51, No. 4, 01.04.2019, p. 472-478.

    Research output: Contribution to journalArticle

    Gröger, M, Wepler, M, Wachter, U, Merz, T, McCook, O, Kress, S, Lukaschewski, B, Hafner, S, Huber-Lang, M, Calzia, E, Georgieff, M, Nagahara, N, Szabo, C, Radermacher, P & Hartmann, C 2019, 'The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock', Shock (Augusta, Ga.), vol. 51, no. 4, pp. 472-478. https://doi.org/10.1097/SHK.0000000000001165
    Gröger, Michael ; Wepler, Martin ; Wachter, Ulrich ; Merz, Tamara ; McCook, Oscar ; Kress, Sandra ; Lukaschewski, Britta ; Hafner, Sebastian ; Huber-Lang, Markus ; Calzia, Enrico ; Georgieff, Michael ; Nagahara, Noriyuki ; Szabo, Csaba ; Radermacher, Peter ; Hartmann, Clair. / The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock. In: Shock (Augusta, Ga.). 2019 ; Vol. 51, No. 4. pp. 472-478.
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    abstract = "INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock. METHODS: Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption. RESULTS: 3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma. CONCLUSIONS: In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.",
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    T1 - The Effects of Genetic 3-Mercaptopyruvate Sulfurtransferase Deficiency in Murine Traumatic-Hemorrhagic Shock

    AU - Gröger, Michael

    AU - Wepler, Martin

    AU - Wachter, Ulrich

    AU - Merz, Tamara

    AU - McCook, Oscar

    AU - Kress, Sandra

    AU - Lukaschewski, Britta

    AU - Hafner, Sebastian

    AU - Huber-Lang, Markus

    AU - Calzia, Enrico

    AU - Georgieff, Michael

    AU - Nagahara, Noriyuki

    AU - Szabo, Csaba

    AU - Radermacher, Peter

    AU - Hartmann, Clair

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    N2 - INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock. METHODS: Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption. RESULTS: 3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma. CONCLUSIONS: In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.

    AB - INTRODUCTION: Hemorrhagic shock is a major cause of death after trauma. An additional blunt chest trauma independently contributes to mortality upon the development of an acute lung injury (ALI) by aggravating pathophysiological consequences of hemorrhagic shock. The maintenance of hydrogen sulfide availability is known to play an important role during hemorrhage and ALI. We therefore tested the impact of a genetic 3-mercaptopyruvate sulfurtransferase mutation (Δ3-MST) in a resuscitated murine model of traumatic-hemorrhagic shock. METHODS: Anesthetized wild-type (WT) and Δ3-MST mice underwent hemorrhagic shock with/without blunt chest trauma. Hemorrhagic shock was implemented for 1 h followed by retransfusion of shed blood and intensive care therapy for 4 h, including lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline titrated to maintain a mean arterial pressure at least 50 mmHg. Systemic hemodynamics, metabolism, and acid-base status were assessed together with lung mechanics and gas exchange. Postmortem tissue samples were analyzed for immunohistological protein expression and mitochondrial oxygen consumption. RESULTS: 3-MST-deficient mice showed similar results in parameters of hemodynamics, gas exchange, metabolism, acid base status, and survival compared with the respective WT controls. Renal albumin extravasation was increased in Δ3-MST mice during hemorrhagic shock, together with a decrease of LEAK respiration in heart tissue. In contrast, mitochondrial oxygen consumption in the uncoupled state was increased in kidney and liver tissue of Δ3-MST mice subjected to the combined trauma. CONCLUSIONS: In summary, in a resuscitated murine model of traumatic-hemorrhagic shock, 3-MST deficiency had no physiologically relevant impact on hemodynamics and metabolism, which ultimately lead to unchanged mortality regardless of an additional blunt chest trauma.

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