Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice

Florian Wagner, Angelika Scheuerle, Sandra Weber, Bettina Stahl, Oscar McCook, Markus W. Knöferl, Markus Huber-Lang, Daniel H. Seitz, Jörg Thomas, Pierre Asfar, Csaba Szabo, Peter Möller, Florian Gebhard, Michael Georgieff, Enrico Calzia, Peter Radermacher, Katja Wagner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background:: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury. Methods:: After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). Result:: Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. CONCLUSIONS:: Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states.

Original languageEnglish (US)
Pages (from-to)1659-1667
Number of pages9
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume71
Issue number6
DOIs
StatePublished - Dec 2011

Fingerprint

Contusions
Cystathionine
Sulfides
Thorax
Hypothermia
Lung
Wounds and Injuries
Lyases
Lung Injury
Heme Oxygenase-1
Caspase 3
Cytokines
Lung Compliance
Hydrogen Sulfide
sodium sulfide
Electrophoretic Mobility Shift Assay
Bradycardia
Heat-Shock Proteins
Acidosis
Mechanics

Keywords

  • Activated caspase-3
  • Apoptosis
  • Cystathionine-β synthase
  • Cystathionine-γ lyase
  • HO-1
  • Hypothermia
  • NF-κB

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice. / Wagner, Florian; Scheuerle, Angelika; Weber, Sandra; Stahl, Bettina; McCook, Oscar; Knöferl, Markus W.; Huber-Lang, Markus; Seitz, Daniel H.; Thomas, Jörg; Asfar, Pierre; Szabo, Csaba; Möller, Peter; Gebhard, Florian; Georgieff, Michael; Calzia, Enrico; Radermacher, Peter; Wagner, Katja.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 71, No. 6, 12.2011, p. 1659-1667.

Research output: Contribution to journalArticle

Wagner, F, Scheuerle, A, Weber, S, Stahl, B, McCook, O, Knöferl, MW, Huber-Lang, M, Seitz, DH, Thomas, J, Asfar, P, Szabo, C, Möller, P, Gebhard, F, Georgieff, M, Calzia, E, Radermacher, P & Wagner, K 2011, 'Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice', Journal of Trauma - Injury, Infection and Critical Care, vol. 71, no. 6, pp. 1659-1667. https://doi.org/10.1097/TA.0b013e318228842e
Wagner, Florian ; Scheuerle, Angelika ; Weber, Sandra ; Stahl, Bettina ; McCook, Oscar ; Knöferl, Markus W. ; Huber-Lang, Markus ; Seitz, Daniel H. ; Thomas, Jörg ; Asfar, Pierre ; Szabo, Csaba ; Möller, Peter ; Gebhard, Florian ; Georgieff, Michael ; Calzia, Enrico ; Radermacher, Peter ; Wagner, Katja. / Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice. In: Journal of Trauma - Injury, Infection and Critical Care. 2011 ; Vol. 71, No. 6. pp. 1659-1667.
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abstract = "Background:: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury. Methods:: After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). Result:: Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. CONCLUSIONS:: Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states.",
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AU - Wagner, Florian

AU - Scheuerle, Angelika

AU - Weber, Sandra

AU - Stahl, Bettina

AU - McCook, Oscar

AU - Knöferl, Markus W.

AU - Huber-Lang, Markus

AU - Seitz, Daniel H.

AU - Thomas, Jörg

AU - Asfar, Pierre

AU - Szabo, Csaba

AU - Möller, Peter

AU - Gebhard, Florian

AU - Georgieff, Michael

AU - Calzia, Enrico

AU - Radermacher, Peter

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N2 - Background:: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury. Methods:: After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). Result:: Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. CONCLUSIONS:: Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states.

AB - Background:: When used as a pretreatment, hydrogen sulfide (H2S) either attenuated or aggravated lung injury. Therefore, we tested the hypothesis whether posttreatment intravenous Na2S (sulfide) may attenuate lung injury. Methods:: After blast wave blunt chest trauma or sham procedure, anesthetized and instrumented mice received continuous intravenous sulfide or vehicle while being kept at 37°C or 32°C core temperature. After 4 hours of pressure-controlled, thoracopulmonary compliance-titrated, lung-protective mechanical ventilation, blood and tissue were harvested for cytokine concentrations, heme oxygenase-1, IκBα, Bcl-Xl, and pBad expression (western blotting), nuclear factor-κB activation (electrophoretic mobility shift assay), and activated caspase-3, cystathionine-β synthase and cystathionine-γ lyase (immunohistochemistry). Result:: Hypothermia caused marked bradycardia and metabolic acidosis unaltered by sulfide. Chest trauma impaired thoracopulmonary compliance and arterial Po2, again without sulfide effect. Cytokine levels showed inconsistent response. Sulfide increased nuclear factor-κB activation during normothermia, but this effect was blunted during hypothermia. While histologic lung injury was variable, both sulfide and hypothermia attenuated the trauma-related increase in heme oxygenase-1 expression and activated caspase-3 staining, which coincided with increased Bad phosphorylation and Bcl-Xl expression. Sulfide and hypothermia also attenuated the trauma-induced cystathionine-β synthase and cystathionine-γ lyase expression. CONCLUSIONS:: Posttreatment sulfide infusion after blunt chest trauma did not affect the impaired lung mechanics and gas exchange but attenuated stress protein expression and apoptotic cell death. This protective effect was amplified by moderate hypothermia. The simultaneous reduction in cystathionine-β synthase and cystathionine-γ lyase expression supports the role of H2S-generating enzymes as an adaptive response during stress states.

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KW - Apoptosis

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KW - HO-1

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KW - NF-κB

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