Cargando…

Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study

The exact contribution of neutrophils to post-resuscitative brain damage is unknown. We aimed to investigate whether neutrophil extracellular trap (NET) formation in the early phase after return of spontaneous circulation (ROSC) may be associated with poor 30 day neurologic function in cardiac arres...

Descripción completa

Detalles Bibliográficos
Autores principales: Mauracher, Lisa-Marie, Buchtele, Nina, Schörgenhofer, Christian, Weiser, Christoph, Herkner, Harald, Merrelaar, Anne, Spiel, Alexander O., Hell, Lena, Ay, Cihan, Pabinger, Ingrid, Jilma, Bernd, Schwameis, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832426/
https://www.ncbi.nlm.nih.gov/pubmed/31581493
http://dx.doi.org/10.3390/jcm8101568
_version_ 1783466169412354048
author Mauracher, Lisa-Marie
Buchtele, Nina
Schörgenhofer, Christian
Weiser, Christoph
Herkner, Harald
Merrelaar, Anne
Spiel, Alexander O.
Hell, Lena
Ay, Cihan
Pabinger, Ingrid
Jilma, Bernd
Schwameis, Michael
author_facet Mauracher, Lisa-Marie
Buchtele, Nina
Schörgenhofer, Christian
Weiser, Christoph
Herkner, Harald
Merrelaar, Anne
Spiel, Alexander O.
Hell, Lena
Ay, Cihan
Pabinger, Ingrid
Jilma, Bernd
Schwameis, Michael
author_sort Mauracher, Lisa-Marie
collection PubMed
description The exact contribution of neutrophils to post-resuscitative brain damage is unknown. We aimed to investigate whether neutrophil extracellular trap (NET) formation in the early phase after return of spontaneous circulation (ROSC) may be associated with poor 30 day neurologic function in cardiac arrest survivors. This study prospectively included adult (≥18 years) out-of-hospital cardiac arrest (OHCA) survivors with cardiac origin, who were subjected to targeted temperature management. Plasma levels of specific (citrullinated histone H3, H3Cit) and putative (cell-free DNA (cfDNA) and nucleosomes) biomarkers of NET formation were assessed at 0 and 12 h after admission. The primary outcome was neurologic function on day 30 after admission, which was assessed using the five-point cerebral performance category (CPC) score, classifying patients into good (CPC 1–2) or poor (CPC 3–5) neurologic function. The main variable of interest was the effect of H3Cit level quintiles at 12 h on 30 day neurologic function, assessed by logistic regression. The first quintile was used as a baseline reference. Results are given as crude odds ratio (OR) with 95% confidence interval (95% CI). Sixty-two patients (79% male, median age: 57 years) were enrolled. The odds of poor neurologic function increased linearly, with 0 h levels of cfNDA (crude OR 1.8, 95% CI: 1.2–2.7, p = 0.007) and nucleosomes (crude OR 1.7, 95% CI: 1.0–2.2, p = 0.049), as well as with 12 h levels of cfDNA (crude OR 1.6, 95% CI: 1.1–2.4, p = 0.024), nucleosomes (crude OR 1.7, 95% CI: 1.1–2.5, p = 0.020), and H3Cit (crude OR 1.6, 95% CI: 1.1–2.3, p = 0.029). Patients in the fourth (7.9, 95% CI: 1.1–56, p = 0.039) and fifth (9.0, 95% CI: 1.3–63, p = 0.027) H3Cit quintile had significantly higher odds of poor 30 day neurologic function compared to patients in the first quintile. Increased plasma levels of H3Cit, 12 h after admission, are associated with poor 30 day neurologic function in adult OHCA survivors, which may suggest a contribution of NET formation to post-resuscitative brain damage and therefore provide a therapeutic target in the future.
format Online
Article
Text
id pubmed-6832426
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68324262019-11-25 Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study Mauracher, Lisa-Marie Buchtele, Nina Schörgenhofer, Christian Weiser, Christoph Herkner, Harald Merrelaar, Anne Spiel, Alexander O. Hell, Lena Ay, Cihan Pabinger, Ingrid Jilma, Bernd Schwameis, Michael J Clin Med Article The exact contribution of neutrophils to post-resuscitative brain damage is unknown. We aimed to investigate whether neutrophil extracellular trap (NET) formation in the early phase after return of spontaneous circulation (ROSC) may be associated with poor 30 day neurologic function in cardiac arrest survivors. This study prospectively included adult (≥18 years) out-of-hospital cardiac arrest (OHCA) survivors with cardiac origin, who were subjected to targeted temperature management. Plasma levels of specific (citrullinated histone H3, H3Cit) and putative (cell-free DNA (cfDNA) and nucleosomes) biomarkers of NET formation were assessed at 0 and 12 h after admission. The primary outcome was neurologic function on day 30 after admission, which was assessed using the five-point cerebral performance category (CPC) score, classifying patients into good (CPC 1–2) or poor (CPC 3–5) neurologic function. The main variable of interest was the effect of H3Cit level quintiles at 12 h on 30 day neurologic function, assessed by logistic regression. The first quintile was used as a baseline reference. Results are given as crude odds ratio (OR) with 95% confidence interval (95% CI). Sixty-two patients (79% male, median age: 57 years) were enrolled. The odds of poor neurologic function increased linearly, with 0 h levels of cfNDA (crude OR 1.8, 95% CI: 1.2–2.7, p = 0.007) and nucleosomes (crude OR 1.7, 95% CI: 1.0–2.2, p = 0.049), as well as with 12 h levels of cfDNA (crude OR 1.6, 95% CI: 1.1–2.4, p = 0.024), nucleosomes (crude OR 1.7, 95% CI: 1.1–2.5, p = 0.020), and H3Cit (crude OR 1.6, 95% CI: 1.1–2.3, p = 0.029). Patients in the fourth (7.9, 95% CI: 1.1–56, p = 0.039) and fifth (9.0, 95% CI: 1.3–63, p = 0.027) H3Cit quintile had significantly higher odds of poor 30 day neurologic function compared to patients in the first quintile. Increased plasma levels of H3Cit, 12 h after admission, are associated with poor 30 day neurologic function in adult OHCA survivors, which may suggest a contribution of NET formation to post-resuscitative brain damage and therefore provide a therapeutic target in the future. MDPI 2019-10-01 /pmc/articles/PMC6832426/ /pubmed/31581493 http://dx.doi.org/10.3390/jcm8101568 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mauracher, Lisa-Marie
Buchtele, Nina
Schörgenhofer, Christian
Weiser, Christoph
Herkner, Harald
Merrelaar, Anne
Spiel, Alexander O.
Hell, Lena
Ay, Cihan
Pabinger, Ingrid
Jilma, Bernd
Schwameis, Michael
Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study
title Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study
title_full Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study
title_fullStr Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study
title_full_unstemmed Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study
title_short Increased Citrullinated Histone H3 Levels in the Early Post-Resuscitative Period Are Associated with Poor Neurologic Function in Cardiac Arrest Survivors—A Prospective Observational Study
title_sort increased citrullinated histone h3 levels in the early post-resuscitative period are associated with poor neurologic function in cardiac arrest survivors—a prospective observational study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832426/
https://www.ncbi.nlm.nih.gov/pubmed/31581493
http://dx.doi.org/10.3390/jcm8101568
work_keys_str_mv AT mauracherlisamarie increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT buchtelenina increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT schorgenhoferchristian increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT weiserchristoph increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT herknerharald increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT merrelaaranne increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT spielalexandero increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT helllena increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT aycihan increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT pabingeringrid increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT jilmabernd increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy
AT schwameismichael increasedcitrullinatedhistoneh3levelsintheearlypostresuscitativeperiodareassociatedwithpoorneurologicfunctionincardiacarrestsurvivorsaprospectiveobservationalstudy