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 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 2009

Fingerprint

Spectrin
Brain Injuries
Canidae
Calpain
Cardiopulmonary Bypass
Nervous System Trauma
Caspase 3
Thoracic Surgery
Cerebrospinal Fluid
Wounds and Injuries
Cell Death
Caspases
Neurologic Manifestations
Immunoblotting
Polyacrylamide Gel Electrophoresis
Peptide Hydrolases
Necrosis
Central Nervous System
Biomarkers
Apoptosis

ASJC Scopus subject areas

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

Cite this

Alpha II-Spectrin Breakdown Products Serve as Novel Markers of Brain Injury Severity in a Canine Model of Hypothermic Circulatory Arrest. / Weiss, Eric S.; Wang, Kevin K W; Allen, Jeremiah G.; Blue, Mary E; Nwakanma, Lois U.; Liu, Ming Cheng; Lange, Mary S.; Berrong, Jennifer; Wilson, Mary Ann Ann; Gott, Vincent L; Troncoso, Juan C; Hayes, Ronald L.; Johnston, Michael V; Baumgartner, William A.

In: Annals of Thoracic Surgery, Vol. 88, No. 2, 08.2009, p. 543-550.

Research output: Contribution to journalArticle

Weiss, Eric S. ; Wang, Kevin K W ; Allen, Jeremiah G. ; Blue, Mary E ; Nwakanma, Lois U. ; Liu, Ming Cheng ; Lange, Mary S. ; Berrong, Jennifer ; Wilson, Mary Ann Ann ; Gott, Vincent L ; Troncoso, Juan C ; Hayes, Ronald L. ; Johnston, Michael V ; Baumgartner, William A. / Alpha II-Spectrin Breakdown Products Serve as Novel Markers of Brain Injury Severity in a Canine Model of Hypothermic Circulatory Arrest. In: Annals of Thoracic Surgery. 2009 ; Vol. 88, No. 2. pp. 543-550.
@article{3127425a02b94a0693e8e34d097a37c8,
title = "Alpha II-Spectrin Breakdown Products Serve as Novel Markers of Brain Injury Severity in a Canine Model of Hypothermic Circulatory Arrest",
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.",
author = "Weiss, {Eric S.} and Wang, {Kevin K W} and Allen, {Jeremiah G.} and Blue, {Mary E} and Nwakanma, {Lois U.} and Liu, {Ming Cheng} and Lange, {Mary S.} and Jennifer Berrong and Wilson, {Mary Ann Ann} and Gott, {Vincent L} and Troncoso, {Juan C} and Hayes, {Ronald L.} and Johnston, {Michael V} and Baumgartner, {William A}",
year = "2009",
month = "8",
doi = "10.1016/j.athoracsur.2009.04.016",
language = "English (US)",
volume = "88",
pages = "543--550",
journal = "Annals of Thoracic Surgery",
issn = "0003-4975",
publisher = "Elsevier USA",
number = "2",

}

TY - JOUR

T1 - Alpha II-Spectrin Breakdown Products Serve as Novel Markers of Brain Injury Severity in a Canine Model of Hypothermic Circulatory Arrest

AU - Weiss, Eric S.

AU - Wang, Kevin K W

AU - Allen, Jeremiah G.

AU - Blue, Mary E

AU - Nwakanma, Lois U.

AU - Liu, Ming Cheng

AU - Lange, Mary S.

AU - Berrong, Jennifer

AU - Wilson, Mary Ann Ann

AU - Gott, Vincent L

AU - Troncoso, Juan C

AU - Hayes, Ronald L.

AU - Johnston, Michael V

AU - Baumgartner, William A

PY - 2009/8

Y1 - 2009/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67650707926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650707926&partnerID=8YFLogxK

U2 - 10.1016/j.athoracsur.2009.04.016

DO - 10.1016/j.athoracsur.2009.04.016

M3 - Article

C2 - 19632410

AN - SCOPUS:67650707926

VL - 88

SP - 543

EP - 550

JO - Annals of Thoracic Surgery

JF - Annals of Thoracic Surgery

SN - 0003-4975

IS - 2

ER -