Journal article

Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation


Authors listEdinger, Fabian; Schmitt, Christoph; Koch, Christian; McIntosh, J. Michael; Janciauskiene, Sabina; Markmann, Melanie; Sander, Michael; Padberg, Winfried; Grau, Veronika

Publication year2021

JournalScientific Reports

Volume number11

Issue number1

ISSN2045-2322

Open access statusGold

DOI Linkhttps://doi.org/10.1038/s41598-021-95119-y

PublisherNature Research


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 alpha 1-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 alpha 1-antitrypsin reduces the release of cytokines in response to 2 h of experimental ECMO. Adult rats were intravenously infused with alpha 1-antitrypsin immediately before starting veno-arterial ECMO. We measured selected pro- and anti-inflammatory cytokines and found, that systemic levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10 increase during experimental ECMO. As tachycardia and hypertension developed in response to alpha 1-antitrypsin, a single additional bolus of fentanyl and midazolam was given. Treatment with alpha 1-antitrypsin and higher sedative doses reduced all cytokine levels investigated. We suggest that alpha 1-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 alpha 1-antitrypsin inhibits cytokine release in vivo and to explore the potential application of alpha 1-antitrypsin in clinical ECMO.



Citation Styles

Harvard Citation styleEdinger, F., Schmitt, C., Koch, C., McIntosh, J., Janciauskiene, S., Markmann, M., et al. (2021) Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation, Scientific Reports, 11(1), Article 15849. https://doi.org/10.1038/s41598-021-95119-y

APA Citation styleEdinger, F., Schmitt, C., Koch, C., McIntosh, J., Janciauskiene, S., Markmann, M., Sander, M., Padberg, W., & Grau, V. (2021). Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation. Scientific Reports. 11(1), Article 15849. https://doi.org/10.1038/s41598-021-95119-y



Keywords


ALPHA(1)-ANTITRYPSINAlpha-1-antitrypsin deficiencyCARDIOPULMONARY BYPASSHUMAN MONOCYTESINFLAMMATORY RESPONSE

Last updated on 2025-10-06 at 11:29