Systemic impact on secondary brain aggravation due to ischemia/reperfusion injury in post-cardiac arrest syndrome: A prospective observational study using high-mobility group box 1 protein

Atsunori Sugita, Kosaku Kinoshita, Atsushi Sakurai, Nobutaka Chiba, Junko Yamaguchi, Tsukasa Kuwana, Nami Sawada, Satoshi Hori

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Background: Ischemia/reperfusion injury (I/R) is an important pathophysiology of post-cardiac arrest syndrome (PCAS) against multiple organ dysfunction and mortality. The inflammatory response in PCAS causes systemic I/R. The purpose of this study was to demonstrate the pathophysiology of systemic I/R for secondary brain damage using the biomarkers high-mobility group box 1 (HMGB1), neuron-specific enolase (NSE), and interleukin-6 (IL-6). Methods: This study was designed as a single-institution prospective observational study. Subjects were observed for 90days, and neurological outcome was classified according to the Glasgow-Pittsburgh Cerebral Performance Categories Scale (CPC). Serum HMGB1, NSE, and IL-6 were evaluated for variability, correlation with each biomarker, or the Sequential Organ Function Assessment (SOFA) score and CPC at return of spontaneous circulation at 0, 24, 48, and 168h. Results: A total of 128 patients were enrolled in this study. Initial HMGB1 correlated with CPC (p=0.27, p=0.036) and SOFA score (p=0.33, p<0.001). The early phase of HMGB1 (0-24h), all phases of IL-6, and the delayed phase of NSE (24-168h) manifested poor neurological outcome. HMGB1 showed a significant correlation with NSE (p=0.29, p=0.002 at 0h; p=0.42, p<0.001 at 24h) and IL-6 (p=0.36, p<0.001 at 24h). Conclusions: Serum HMGB1 for first 24h after cardiac arrest was significantly correlated with SOFA score, NSE, and IL-6. This result suggests that systemic I/R may contribute to secondary brain aggravation. It is expected that research on HMGB1 focused on systemic I/R will help prevent aggravating neurological outcomes.

Original languageEnglish
Article number247
JournalCritical Care
Volume21
Issue number1
DOIs
Publication statusPublished - 26 Sept 2017

Keywords

  • HMGB1
  • IL-6
  • NSE
  • Post-cardiac arrest syndrome
  • SOFA score
  • Secondary brain injury
  • Systemic ischemia/reperfusion injury

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