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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Fabian Edinger, Christoph Schmitt, Christian Koch, J. Michael McIntosh, Sabina Janciauskiene, Melanie Markmann, Michael Sander, Winfried Padberg, Veronika Grau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/44e41d8a7d1447bc9dba3cdba4e8e8d2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:44e41d8a7d1447bc9dba3cdba4e8e8d2
record_format	dspace
spelling	oai:doaj.org-article:44e41d8a7d1447bc9dba3cdba4e8e8d22021-12-02T18:49:23ZApplication of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation10.1038/s41598-021-95119-y2045-2322https://doaj.org/article/44e41d8a7d1447bc9dba3cdba4e8e8d22021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95119-yhttps://doaj.org/toc/2045-2322Abstract 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.Fabian EdingerChristoph SchmittChristian KochJ. Michael McIntoshSabina JanciauskieneMelanie MarkmannMichael SanderWinfried PadbergVeronika GrauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/44e41d8a7d1447bc9dba3cdba4e8e8d2
work_keys_str_mv	AT fabianedinger applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT christophschmitt applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT christiankoch applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT jmichaelmcintosh applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT sabinajanciauskiene applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT melaniemarkmann applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT michaelsander applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT winfriedpadberg applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation AT veronikagrau applicationofalpha1antitrypsininaratmodelofvenoarterialextracorporealmembraneoxygenation
_version_	1718377557206761472

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

Ejemplares similares