Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage
Abstract Background In murine models, controversial data have been reported on the effect of hydrogen sulfide (H2S) administration during resuscitation from trauma-and-hemorrhage. The H2S donor sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, and, hence, we determined...
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2025-08-01
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| Online Access: | https://doi.org/10.1186/s40635-025-00778-0 |
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| author | Maximilian Feth Mirabel Gracco Michael Gröger Melanie Hogg Sandra Kress Andrea Hoffmann Enrico Calzia Ulrich Wachter Peter Radermacher Tamara Merz |
| author_facet | Maximilian Feth Mirabel Gracco Michael Gröger Melanie Hogg Sandra Kress Andrea Hoffmann Enrico Calzia Ulrich Wachter Peter Radermacher Tamara Merz |
| author_sort | Maximilian Feth |
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| description | Abstract Background In murine models, controversial data have been reported on the effect of hydrogen sulfide (H2S) administration during resuscitation from trauma-and-hemorrhage. The H2S donor sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, and, hence, we determined its effects in our full scale ICU-model of resuscitated murine trauma-and-hemorrhage. We hypothesized that Na2S2O3 might improve energy metabolism and thereby exert organ-protective effects as previously demonstrated in animals with genetic cystathionine-γ-lyase (CSE) deletion (CSE−/−). Methods 30 mice underwent combined blast wave-induced blunt chest trauma followed by 1 h of hemorrhagic shock (mean arterial pressure MAP = 35 ± 5 mmHg). Thereafter, resuscitation was initiated comprising re-transfusion of shed blood, lung-protective mechanical ventilation, fluid resuscitation and continuous i.v. noradrenaline infusion to maintain MAP > 55 mmHg over 6 h, and randomized administration of either i.v. 0.45 mg/gbodyweight Na2S2O3 or vehicle (NaCl 0.9%). Hemodynamics, lung mechanics, gas exchange, acid–base-status and organ function parameters were recorded. Metabolic pathways were quantified based on gas chromatography/mass spectrometry assessment of plasma isotope enrichment during primed-continuous infusion of stable, non-radioactive, isotope labeled substrates. Mitochondrial function was determined using high-resolution respirometry, and tissue target proteins (nitrotyrosine formation, extravascular albumin accumulation, CSE expression) were analyzed using immunohistochemistry. Results Data originate from 23 mice (Na2S2O3 n = 12; vehicle n = 11). Na2S2O3 affected neither survival nor noradrenaline requirements. While minute ventilation had to be increased over time in both groups to maintain arterial PCO2 without intergroup difference, arterial PO2 decreased over time in Na2S2O3-treated mice (p = 0.006). Although arterial pH decreased in both groups (vehicle p = 0.049; Na2S2O3 p < 0.001), metabolic acidosis was more pronounced in the Na2S2O3 group. Neither metabolic pathways nor tissue mitochondrial respiratory activity or tissue target proteins showed any intergroup differences. Discussion In this model of resuscitated trauma-and-hemorrhage, Na2S2O3 did not exert any beneficial metabolic or organ-protective effect and was even associated with impaired pulmonary function. These results are in contrast to our previous findings in CSE−/− mice, but in line with more recent findings in CSE−/− mice with pre-existing comorbidities. Hence, our studies do not support a beneficial role of Na2S2O3 in trauma resuscitation. |
| format | Article |
| id | doaj-art-e857bbce3e41487e849fd6ed94f3eaa9 |
| institution | Kabale University |
| issn | 2197-425X |
| language | English |
| publishDate | 2025-08-01 |
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| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-e857bbce3e41487e849fd6ed94f3eaa92025-08-20T03:42:39ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2025-08-0113111310.1186/s40635-025-00778-0Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhageMaximilian Feth0Mirabel Gracco1Michael Gröger2Melanie Hogg3Sandra Kress4Andrea Hoffmann5Enrico Calzia6Ulrich Wachter7Peter Radermacher8Tamara Merz9Department of Anesthesiology, Critical Care, Emergency Medicine and Pain Therapy, German Armed Forces Hospital UlmInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalInstitute for Anesthesiological Pathohysiology and Process Engineering, Ulm University HospitalAbstract Background In murine models, controversial data have been reported on the effect of hydrogen sulfide (H2S) administration during resuscitation from trauma-and-hemorrhage. The H2S donor sodium thiosulfate (Na2S2O3) is a recognized drug devoid of major side effects, and, hence, we determined its effects in our full scale ICU-model of resuscitated murine trauma-and-hemorrhage. We hypothesized that Na2S2O3 might improve energy metabolism and thereby exert organ-protective effects as previously demonstrated in animals with genetic cystathionine-γ-lyase (CSE) deletion (CSE−/−). Methods 30 mice underwent combined blast wave-induced blunt chest trauma followed by 1 h of hemorrhagic shock (mean arterial pressure MAP = 35 ± 5 mmHg). Thereafter, resuscitation was initiated comprising re-transfusion of shed blood, lung-protective mechanical ventilation, fluid resuscitation and continuous i.v. noradrenaline infusion to maintain MAP > 55 mmHg over 6 h, and randomized administration of either i.v. 0.45 mg/gbodyweight Na2S2O3 or vehicle (NaCl 0.9%). Hemodynamics, lung mechanics, gas exchange, acid–base-status and organ function parameters were recorded. Metabolic pathways were quantified based on gas chromatography/mass spectrometry assessment of plasma isotope enrichment during primed-continuous infusion of stable, non-radioactive, isotope labeled substrates. Mitochondrial function was determined using high-resolution respirometry, and tissue target proteins (nitrotyrosine formation, extravascular albumin accumulation, CSE expression) were analyzed using immunohistochemistry. Results Data originate from 23 mice (Na2S2O3 n = 12; vehicle n = 11). Na2S2O3 affected neither survival nor noradrenaline requirements. While minute ventilation had to be increased over time in both groups to maintain arterial PCO2 without intergroup difference, arterial PO2 decreased over time in Na2S2O3-treated mice (p = 0.006). Although arterial pH decreased in both groups (vehicle p = 0.049; Na2S2O3 p < 0.001), metabolic acidosis was more pronounced in the Na2S2O3 group. Neither metabolic pathways nor tissue mitochondrial respiratory activity or tissue target proteins showed any intergroup differences. Discussion In this model of resuscitated trauma-and-hemorrhage, Na2S2O3 did not exert any beneficial metabolic or organ-protective effect and was even associated with impaired pulmonary function. These results are in contrast to our previous findings in CSE−/− mice, but in line with more recent findings in CSE−/− mice with pre-existing comorbidities. Hence, our studies do not support a beneficial role of Na2S2O3 in trauma resuscitation.https://doi.org/10.1186/s40635-025-00778-0H2SOxidative stressNitrosative stressMitochondrial functionStable isotopesMetabolism |
| spellingShingle | Maximilian Feth Mirabel Gracco Michael Gröger Melanie Hogg Sandra Kress Andrea Hoffmann Enrico Calzia Ulrich Wachter Peter Radermacher Tamara Merz Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage Intensive Care Medicine Experimental H2S Oxidative stress Nitrosative stress Mitochondrial function Stable isotopes Metabolism |
| title | Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage |
| title_full | Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage |
| title_fullStr | Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage |
| title_full_unstemmed | Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage |
| title_short | Sodium thiosulfate does not affect energy metabolism or organ (dys)function during resuscitation from murine trauma-and-hemorrhage |
| title_sort | sodium thiosulfate does not affect energy metabolism or organ dys function during resuscitation from murine trauma and hemorrhage |
| topic | H2S Oxidative stress Nitrosative stress Mitochondrial function Stable isotopes Metabolism |
| url | https://doi.org/10.1186/s40635-025-00778-0 |
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