Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation
Abstract Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients suffering from respiratory or cardiac failure. The ECMO-associated morbidity and mortality depends to a large extent on the underlying disease and is often related to systemic inflammation, consecutive imm...
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| Format: | Article |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-95119-y |
| _version_ | 1818855978079092736 |
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| author | Fabian Edinger Christoph Schmitt Christian Koch J. Michael McIntosh Sabina Janciauskiene Melanie Markmann Michael Sander Winfried Padberg Veronika Grau |
| author_facet | Fabian Edinger Christoph Schmitt Christian Koch J. Michael McIntosh Sabina Janciauskiene Melanie Markmann Michael Sander Winfried Padberg Veronika Grau |
| author_sort | Fabian Edinger |
| collection | DOAJ |
| description | Abstract Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients suffering from respiratory or cardiac failure. The ECMO-associated morbidity and mortality depends to a large extent on the underlying disease and is often related to systemic inflammation, consecutive immune paralysis and sepsis. Here we tested the hypothesis that human α1-antitrypsin (SERPINA1) due to its anti-protease and anti-inflammatory functions may attenuate ECMO-induced inflammation. We specifically aimed to test whether intravenous treatment with α1-antitrypsin reduces the release of cytokines in response to 2 h of experimental ECMO. Adult rats were intravenously infused with α1-antitrypsin immediately before starting veno-arterial ECMO. We measured selected pro- and anti-inflammatory cytokines and found, that systemic levels of tumor necrosis factor-α, interleukin-6 and interleukin-10 increase during experimental ECMO. As tachycardia and hypertension developed in response to α1-antitrypsin, a single additional bolus of fentanyl and midazolam was given. Treatment with α1-antitrypsin and higher sedative doses reduced all cytokine levels investigated. We suggest that α1-antitrypsin might have the potential to protect against both ECMO-induced systemic inflammation and immune paralysis. More studies are needed to corroborate our findings, to clarify the mechanisms by which α1-antitrypsin inhibits cytokine release in vivo and to explore the potential application of α1-antitrypsin in clinical ECMO. |
| first_indexed | 2024-12-19T08:17:11Z |
| format | Article |
| id | doaj.art-44e41d8a7d1447bc9dba3cdba4e8e8d2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:17:11Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-44e41d8a7d1447bc9dba3cdba4e8e8d22022-12-21T20:29:27ZengNature PortfolioScientific Reports2045-23222021-08-0111111410.1038/s41598-021-95119-yApplication of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenationFabian Edinger0Christoph Schmitt1Christian Koch2J. Michael McIntosh3Sabina Janciauskiene4Melanie Markmann5Michael Sander6Winfried Padberg7Veronika Grau8Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig University of GiessenDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig University of GiessenDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig University of GiessenGeorge E. Wahlen Veterans Affairs Medical CenterDepartment of Respiratory Medicine, Hannover Medical School, German Centre for Lung Research (DZL)Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig University of GiessenDepartment of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus-Liebig University of GiessenLaboratory of Experimental Surgery, Department of General and Thoracic Surgery, German Centre for Lung Research (DZL), Justus-Liebig-University of GiessenLaboratory of Experimental Surgery, Department of General and Thoracic Surgery, German Centre for Lung Research (DZL), Justus-Liebig-University of GiessenAbstract Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients suffering from respiratory or cardiac failure. The ECMO-associated morbidity and mortality depends to a large extent on the underlying disease and is often related to systemic inflammation, consecutive immune paralysis and sepsis. Here we tested the hypothesis that human α1-antitrypsin (SERPINA1) due to its anti-protease and anti-inflammatory functions may attenuate ECMO-induced inflammation. We specifically aimed to test whether intravenous treatment with α1-antitrypsin reduces the release of cytokines in response to 2 h of experimental ECMO. Adult rats were intravenously infused with α1-antitrypsin immediately before starting veno-arterial ECMO. We measured selected pro- and anti-inflammatory cytokines and found, that systemic levels of tumor necrosis factor-α, interleukin-6 and interleukin-10 increase during experimental ECMO. As tachycardia and hypertension developed in response to α1-antitrypsin, a single additional bolus of fentanyl and midazolam was given. Treatment with α1-antitrypsin and higher sedative doses reduced all cytokine levels investigated. We suggest that α1-antitrypsin might have the potential to protect against both ECMO-induced systemic inflammation and immune paralysis. More studies are needed to corroborate our findings, to clarify the mechanisms by which α1-antitrypsin inhibits cytokine release in vivo and to explore the potential application of α1-antitrypsin in clinical ECMO.https://doi.org/10.1038/s41598-021-95119-y |
| spellingShingle | Fabian Edinger Christoph Schmitt Christian Koch J. Michael McIntosh Sabina Janciauskiene Melanie Markmann Michael Sander Winfried Padberg Veronika Grau Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation Scientific Reports |
| title | Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation |
| title_full | Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation |
| title_fullStr | Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation |
| title_full_unstemmed | Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation |
| title_short | Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation |
| title_sort | application of alpha1 antitrypsin in a rat model of veno arterial extracorporeal membrane oxygenation |
| url | https://doi.org/10.1038/s41598-021-95119-y |
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