Inflammatory profile in a canine model of hypothermic circulatory arrest

Katherine Giuliano, Sylvia Torres-Odio, Eric Etchill, Patrice Carr, C. Conover Talbot, Mary E. Blue, Michael V. Johnston, William A. Baumgartner, Jennifer S. Lawton, Mary Ann Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Hypothermic circulatory arrest (HCA) is a technique used for complex repair of the aorta, but it can be associated with neurologic morbidity. To better understand the molecular changes that underlie ischemic brain injury, we assessed gene expression and cytokine/chemokine polypeptide concentration in brain tissue and cerebrospinal fluid (CSF) of canines that underwent two hours of HCA. Materials and Methods: Adult male canines were cannulated peripherally for cardiopulmonary bypass, cooled to 18°C, and arrested for two hours. Animals were euthanized two, eight, or 24 hours post-HCA (n = 8 per group), and their brains were compared to brains from eight normal canines, using gene expression microarray analysis, cytokine assay, and histopathology. Results: Two to eight hours after HCA, pro-inflammatory cytokine mRNAs increased markedly, and gene expression was enriched within signaling pathways related to neuroinflammation or ischemic injury. Concentrations of pro-inflammatory cytokine polypeptides IL-6, IL-8, IL-1β, and CCL2 were very low in normal canine brain, whereas anti-inflammatory IL-10 and TGF-β1 were expressed at moderate levels. Pro-inflammatory cytokine concentrations rose robustly in cerebral tissue and CSF after HCA. IL-6 and IL-8 peaked at eight hours and declined at 24 hours, while IL-1β and CCL2 remained elevated. Concentrations of anti-inflammatory IL-10 and TGF-β1 were maintained after HCA, with a significant increase in TGF-β1 at 24 hours. Conclusions: These cytokines represent potential diagnostic markers for ischemic neurologic injury that could be used to assess neurologic injury in patients undergoing HCA. The cellular mechanisms underlying this pro-inflammatory, ischemic-induced injury represent potential targets for neuroprotection in the future.

Original languageEnglish (US)
Pages (from-to)260-273
Number of pages14
JournalJournal of Surgical Research
Volume264
DOIs
StatePublished - Aug 2021

Keywords

  • Anti-inflammatory cytokines
  • Biomarkers of neurologic injury
  • Hypothermic circulatory arrest
  • Ischemic brain injury
  • Neuroinflammation
  • Neurologic injury
  • Pro-inflammatory cytokines

ASJC Scopus subject areas

  • Surgery

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