Alpha II-Spectrin Breakdown Products Serve as Novel Markers of Brain Injury Severity in a Canine Model of Hypothermic Circulatory Arrest

Eric S. Weiss, Kevin K.W. Wang, Jeremiah G. Allen, Mary E. Blue, Lois U. Nwakanma, Ming Cheng Liu, Mary S. Lange, Jennifer Berrong, Mary Ann Wilson, Vincent L. Gott, Juan C. Troncoso, Ronald L. Hayes, Michael V. Johnston, William A. Baumgartner

Research output: Contribution to journalArticle

Abstract

Background: The development of specific biomarkers to aid in the diagnosis and prognosis of neuronal injury is of paramount importance in cardiac surgery. Alpha II-spectrin is a structural protein abundant in neurons of the central nervous system and cleaved into signature fragments by proteases involved in necrotic and apoptotic cell death. We measured cerebrospinal fluid alpha II-spectrin breakdown products (αII-SBDPs) in a canine model of hypothermic circulatory arrest (HCA) and cardiopulmonary bypass. Methods: Canine subjects were exposed to either 1 hour of HCA (n = 8; mean lowest tympanic temperature 18.0 ± 1.2°C) or standard cardiopulmonary bypass (n = 7). Cerebrospinal fluid samples were collected before treatment and 8 and 24 hours after treatment. Using polyacrylamide gel electrophoresis and immunoblotting, SBDPs were isolated and compared between groups using computer-assisted densitometric scanning. Necrotic versus apoptotic cell death was indexed by measuring calpain and caspase-3 cleaved αII-SBDPs (SBDP 145+150 and SBDP 120, respectively). Results: Animals undergoing HCA demonstrated mild patterns of histologic cellular injury and clinically detectable neurologic dysfunction. Calpain-produced αII-SBDPs (150 kDa+145 kDa bands-necrosis) 8 hours after HCA were significantly increased (p = 0.02) as compared with levels before HCA, and remained elevated at 24 hours after HCA. In contrast, caspase-3 αII-SBDP (120 kDa band-apoptosis) was not significantly increased. Animals receiving cardiopulmonary bypass did not demonstrate clinical or histologic evidence of injury, with no increases in necrotic or apoptotic cellular markers. Conclusions: We report the use of αII-SBDPs as markers of neurologic injury after cardiac surgery. Our analysis demonstrates that calpain- and caspase-produced αII-SBDPs may be an important and novel marker of neurologic injury after HCA.

Original languageEnglish (US)
Pages (from-to)543-550
Number of pages8
JournalAnnals of Thoracic Surgery
Volume88
Issue number2
DOIs
StatePublished - Aug 1 2009

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Alpha II-Spectrin Breakdown Products Serve as Novel Markers of Brain Injury Severity in a Canine Model of Hypothermic Circulatory Arrest'. Together they form a unique fingerprint.

  • Cite this