Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function
IntroductionWe previously showed that attenuated glucocorticoid receptor (GR) function in mice (GRdim/dim) aggravates systemic hypotension and impairs organ function during endotoxic shock. Hemorrhagic shock (HS) causes impaired organ perfusion, which leads to tissue hypoxia and inflammation with ri...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.980707/full |
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| author | Martin Wepler Martin Wepler Jonathan M. Preuss Cornelia Tilp Martina Keck Jochen Blender Ulrich Wachter Tamara Merz Josef Vogt Sandra Kress Michael Gröger Andrea Hoffmann Marina Fink Enrico Calzia Ute Burret Peter Radermacher Jan P. Tuckermann Sabine Vettorazzi |
| author_facet | Martin Wepler Martin Wepler Jonathan M. Preuss Cornelia Tilp Martina Keck Jochen Blender Ulrich Wachter Tamara Merz Josef Vogt Sandra Kress Michael Gröger Andrea Hoffmann Marina Fink Enrico Calzia Ute Burret Peter Radermacher Jan P. Tuckermann Sabine Vettorazzi |
| author_sort | Martin Wepler |
| collection | DOAJ |
| description | IntroductionWe previously showed that attenuated glucocorticoid receptor (GR) function in mice (GRdim/dim) aggravates systemic hypotension and impairs organ function during endotoxic shock. Hemorrhagic shock (HS) causes impaired organ perfusion, which leads to tissue hypoxia and inflammation with risk of organ failure. Lung co-morbidities like chronic obstructive pulmonary disease (COPD) can aggravate tissue hypoxia via alveolar hypoxia. The most common cause for COPD is cigarette smoke (CS) exposure. Therefore, we hypothesized that affecting GR function in mice (GRdim/dim) and pre-traumatic CS exposure would further impair hemodynamic stability and organ function after HS.MethodsAfter 3 weeks of CS exposure, anesthetized and mechanically ventilated GRdim/dim and GR+/+ mice underwent pressure-controlled HS for 1h via blood withdrawal (mean arterial pressure (MAP) 35mmHg), followed by 4h of resuscitation with re-transfusion of shed blood, colloid fluid infusion and, if necessary, continuous intravenous norepinephrine. Acid–base status and organ function were assessed together with metabolic pathways. Blood and organs were collected at the end of the experiment for analysis of cytokines, corticosterone level, and mitochondrial respiratory capacity. Data is presented as median and interquartile range.ResultsNor CS exposure neither attenuated GR function affected survival. Non-CS GRdim/dim mice had a higher need of norepinephrine to keep target hemodynamics compared to GR+/+ mice. In contrast, after CS exposure norepinephrine need did not differ significantly between GRdim/dim and GR+/+ mice. Non-CS GRdim/dim mice presented with a lower pH and increased blood lactate levels compared to GR+/+ mice, but not CS exposed mice. Also, higher plasma concentrations of some pro-inflammatory cytokines were observed in non-CS GRdim/dim compared to GR+/+ mice, but not in the CS group. With regards to metabolic measurements, CS exposure led to an increased lipolysis in GRdim/dim compared to GR+/+ mice, but not in non-CS exposed animals.ConclusionWhether less metabolic acidosis or increased lipolysis is the reason or the consequence for the trend towards lower catecholamine need in CS exposed GRdim/dim mice warrants further investigation. |
| first_indexed | 2024-04-12T04:44:23Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T04:44:23Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-23e5c3a8c9d64ee397a1cb91a3748c372022-12-22T03:47:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.980707980707Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor functionMartin Wepler0Martin Wepler1Jonathan M. Preuss2Cornelia Tilp3Martina Keck4Jochen Blender5Ulrich Wachter6Tamara Merz7Josef Vogt8Sandra Kress9Michael Gröger10Andrea Hoffmann11Marina Fink12Enrico Calzia13Ute Burret14Peter Radermacher15Jan P. Tuckermann16Sabine Vettorazzi17Department of Anesthesiology and Intensive Care Medicine, University Hospital, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute of Comparative Molecular Endocrinology (CME), Ulm University, Ulm, GermanyImmunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, GermanyImmunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, GermanyImmunology and Respiratory, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute of Comparative Molecular Endocrinology (CME), Ulm University, Ulm, GermanyInstitute for Anesthesiologic Pathophysiology and Process Engineering, Ulm University, Ulm, GermanyInstitute of Comparative Molecular Endocrinology (CME), Ulm University, Ulm, GermanyInstitute of Comparative Molecular Endocrinology (CME), Ulm University, Ulm, GermanyIntroductionWe previously showed that attenuated glucocorticoid receptor (GR) function in mice (GRdim/dim) aggravates systemic hypotension and impairs organ function during endotoxic shock. Hemorrhagic shock (HS) causes impaired organ perfusion, which leads to tissue hypoxia and inflammation with risk of organ failure. Lung co-morbidities like chronic obstructive pulmonary disease (COPD) can aggravate tissue hypoxia via alveolar hypoxia. The most common cause for COPD is cigarette smoke (CS) exposure. Therefore, we hypothesized that affecting GR function in mice (GRdim/dim) and pre-traumatic CS exposure would further impair hemodynamic stability and organ function after HS.MethodsAfter 3 weeks of CS exposure, anesthetized and mechanically ventilated GRdim/dim and GR+/+ mice underwent pressure-controlled HS for 1h via blood withdrawal (mean arterial pressure (MAP) 35mmHg), followed by 4h of resuscitation with re-transfusion of shed blood, colloid fluid infusion and, if necessary, continuous intravenous norepinephrine. Acid–base status and organ function were assessed together with metabolic pathways. Blood and organs were collected at the end of the experiment for analysis of cytokines, corticosterone level, and mitochondrial respiratory capacity. Data is presented as median and interquartile range.ResultsNor CS exposure neither attenuated GR function affected survival. Non-CS GRdim/dim mice had a higher need of norepinephrine to keep target hemodynamics compared to GR+/+ mice. In contrast, after CS exposure norepinephrine need did not differ significantly between GRdim/dim and GR+/+ mice. Non-CS GRdim/dim mice presented with a lower pH and increased blood lactate levels compared to GR+/+ mice, but not CS exposed mice. Also, higher plasma concentrations of some pro-inflammatory cytokines were observed in non-CS GRdim/dim compared to GR+/+ mice, but not in the CS group. With regards to metabolic measurements, CS exposure led to an increased lipolysis in GRdim/dim compared to GR+/+ mice, but not in non-CS exposed animals.ConclusionWhether less metabolic acidosis or increased lipolysis is the reason or the consequence for the trend towards lower catecholamine need in CS exposed GRdim/dim mice warrants further investigation.https://www.frontiersin.org/articles/10.3389/fimmu.2022.980707/fullcatecholaminescigarettes smoke exposureglucocorticoid receptor functionhemodynamic functionhemorrhagic shockmetabolic function |
| spellingShingle | Martin Wepler Martin Wepler Jonathan M. Preuss Cornelia Tilp Martina Keck Jochen Blender Ulrich Wachter Tamara Merz Josef Vogt Sandra Kress Michael Gröger Andrea Hoffmann Marina Fink Enrico Calzia Ute Burret Peter Radermacher Jan P. Tuckermann Sabine Vettorazzi Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function Frontiers in Immunology catecholamines cigarettes smoke exposure glucocorticoid receptor function hemodynamic function hemorrhagic shock metabolic function |
| title | Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function |
| title_full | Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function |
| title_fullStr | Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function |
| title_full_unstemmed | Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function |
| title_short | Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function |
| title_sort | cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function |
| topic | catecholamines cigarettes smoke exposure glucocorticoid receptor function hemodynamic function hemorrhagic shock metabolic function |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.980707/full |
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