title: Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice.
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).
  
  
  RESULTS
  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.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum Ulm, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Angelika
authors.initials: A
authors.lastname: Scheuerle
authors.forename: Sandra
authors.initials: S
authors.lastname: Weber
authors.forename: Bettina
authors.initials: B
authors.lastname: Stahl
authors.forename: Oscar
authors.initials: O
authors.lastname: McCook
authors.forename: Markus W
authors.initials: MW
authors.lastname: Knöferl
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Seitz
authors.forename: Jörg
authors.initials: J
authors.lastname: Thomas
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Florian
authors.initials: F
authors.lastname: Gebhard
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Katja
authors.initials: K
authors.lastname: Wagner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D055370:Lung Injury / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D015656:Respiratory Mechanics / Q000187:drug effects; D012680:Sensitivity and Specificity; D013440:Sulfides / Q000494:pharmacology*; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000473:pathology
chemical_list: D016207:Cytokines; D013440:Sulfides; C033479:sodium sulfide