Brain injury in canine models of cardiac surgery

Mary E. Blue, Mary Ann Wilson, Claude A. Beaty, Timothy J. George, George J. Arnaoutakis, Kara A. Haggerty, Melissa Jones, Jeffrey Brawn, Shaliza Manmohan, Mary S. Lange, Michael V. Johnston, William A. Baumgartner, Juan C. Troncoso

Research output: Contribution to journalArticle

Abstract

Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18-C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of the hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24 hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that, with longer survival time, the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans andmay help explain the subtle cognitive changes experienced by patients after CPB.

Original languageEnglish (US)
Pages (from-to)1134-1143
Number of pages10
JournalJournal of neuropathology and experimental neurology
Volume73
Issue number12
DOIs
StatePublished - Dec 8 2014

Keywords

  • Cardiopulmonary bypass
  • Circulatory arrest
  • Histopathology
  • Hypothermia
  • Hypoxia
  • Ischemia
  • Neurologic deficit score

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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