Alpha II-spectrin breakdown products serve as novel markers of brain injury severity in a canine model of hypothermic circulatory arrest.

Mark McIntosh,'s picture
PubMed URL:
Baumgartner WA
Author List: 
Weiss ES
Wang KK
Allen JG
Blue ME
Nwakanma LU
Liu MC
Lange MS
Berrong J
Wilson MA
Gott VL
Troncoso JC
Hayes RL
Johnston MV
Baumgartner WA
Ann Thorac Surg
PubMed ID: 
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 (alphaII-SBDPs) in a canine model of hypothermic circulatory arrest (HCA) and cardiopulmonary bypass.Canine subjects were exposed to either 1 hour of HCA (n = 8; mean lowest tympanic temperature 18.0 +/- 1.2 degrees 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 alphaII-SBDPs (SBDP 145+150 and SBDP 120, respectively).Animals undergoing HCA demonstrated mild patterns of histologic cellular injury and clinically detectable neurologic dysfunction. Calpain-produced alphaII-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 alphaII-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.We report the use of alphaII-SBDPs as markers of neurologic injury after cardiac surgery. Our analysis demonstrates that calpain- and caspase-produced alphaII-SBDPs may be an important and novel marker of neurologic injury after HCA.
Published Date: 
August, 2009

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