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Article

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

1
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria
2
Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
3
Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, Austria
4
I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(10), 1568; https://doi.org/10.3390/jcm8101568
Received: 29 August 2019 / Revised: 23 September 2019 / Accepted: 24 September 2019 / Published: 1 October 2019
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. View Full-Text
Keywords: neutrophil extracellular traps; citrullinated histone H3; cardiac arrest; neurologic function neutrophil extracellular traps; citrullinated histone H3; cardiac arrest; neurologic function
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MDPI and ACS Style

Mauracher, L.-M.; Buchtele, N.; Schörgenhofer, C.; Weiser, C.; Herkner, H.; Merrelaar, A.; Spiel, A.O.; Hell, L.; Ay, C.; Pabinger, I.; Jilma, B.; Schwameis, M. 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. J. Clin. Med. 2019, 8, 1568. https://doi.org/10.3390/jcm8101568

AMA Style

Mauracher L-M, Buchtele N, Schörgenhofer C, Weiser C, Herkner H, Merrelaar A, Spiel AO, Hell L, Ay C, Pabinger I, Jilma B, Schwameis M. 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. Journal of Clinical Medicine. 2019; 8(10):1568. https://doi.org/10.3390/jcm8101568

Chicago/Turabian Style

Mauracher, Lisa-Marie, Nina Buchtele, Christian Schörgenhofer, Christoph Weiser, Harald Herkner, Anne Merrelaar, Alexander O. Spiel, Lena Hell, Cihan Ay, Ingrid Pabinger, Bernd Jilma, and Michael Schwameis. 2019. "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" Journal of Clinical Medicine 8, no. 10: 1568. https://doi.org/10.3390/jcm8101568

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