Effects of Sodium Thiosulfate During Resuscitation From Trauma-and-Hemorrhage in Cystathionine Gamma Lyase (CSE) Knockout Mice.

Autor:	Gröger M; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Hogg M; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Abdelsalam E; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Kress S; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Hoffmann A; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Stahl B; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Saub V; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Denoix N; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany.; Psychosomatic Medicine and Psychotherapy Clinic, University Hospital Ulm, Germany., McCook O; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Calzia E; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Wolfschmitt EM; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Wachter U; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany.; Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Germany., Vogt JA; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Wang R; Faculty of Science, York University, Toronto, ON, Canada., Radermacher P; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Merz T; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany., Nussbaum BL; Institute for Anaesthesiologic Pathophysiology and Process Engineering, University Hospital Ulm, Germany.; Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Germany.
Jazyk:	angličtina
Zdroj:	Shock (Augusta, Ga.) [Shock] 2022 Jan 01; Vol. 57 (1), pp. 131-139.
DOI:	10.1097/SHK.0000000000001828
Abstrakt:	Background: Sodium thiosulfate (Na2S2O3) is a clinically established drug with antioxidant and sulphide-releasing properties. Na2S2O3 mediated neuro- and cardioprotective effects in ischemia/reperfusion models and anti-inflammatory effects in LPS-induced acute lung injury. Moreover, Na2S2O3 improved lung function during resuscitation from hemorrhagic shock in swine with pre-existing atherosclerosis, characterized by decreased expression of cystathionine γ-lyase (CSE), a major source of hydrogen sulfide (H2S) synthesis in the vasculature. Based on these findings, we investigated the effects of Na2S2O3 administration during resuscitation from trauma-and-hemorrhage in mice under conditions of whole body CSE deficit. Methods: After blast wave-induced blunt chest trauma and surgical instrumentation, CSE knockout (CSE-/-) mice underwent 1 h of hemorrhagic shock (MAP 35 ± 5 mm Hg). At the beginning of resuscitation comprising retransfusion, norepinephrine support and lung-protective mechanical ventilation, animals received either i.v. Na2S2O3 (0.45 mg g-1, n = 12) or vehicle (saline, n = 13). Hemodynamics, acid-base status, metabolism using stable isotopes, and visceral organ function were assessed. Blood and organs were collected for analysis of cytokines, mitochondrial respiratory capacity, and immunoblotting. Results: Na2S2O3 treatment improved arterial paO2 (P = 0.03) coinciding with higher lung tissue glucocorticoid receptor expression. Norepinephrine requirements were lower in the Na2S2O3 group (P < 0.05), which was associated with lower endogenous glucose production and higher urine output. Na2S2O3 significantly increased renal tissue IκBα and heme oxygenase-1 expression, whereas it lowered kidney IL-6 and MCP-1 levels. Conclusion: Na2S2O3 exerted beneficial effects during resuscitation of murine trauma-and-hemorrhage in CSE-/- mice, confirming and extending the previously described organ-protective and anti-inflammatory properties of Na2S2O3. The findings make Na2S2O3 a potentially promising therapeutic option in the context of impaired CSE activity and/or reduced endogenous H2S availability. Competing Interests: The authors report no conflicts of interest. (Copyright © 2021 by the Shock Society.)
Databáze:	MEDLINE
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