JTCS Click here to go to SJM website.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Faraz Kerendi
Michael E. Halkos
Joel S. Corvera
Jakob Vinten-Johansen
Zhi-Qing Zhao
Joseph M. Forbess
Kirk R. Kanter
Paul M. Kirshbom
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kerendi, F.
Right arrow Articles by Kirshbom, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kerendi, F.
Right arrow Articles by Kirshbom, P. M.

J Thorac Cardiovasc Surg 2005;130:1079
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Upregulation of hypoxia inducible factor is associated with attenuation of neuronal injury in neonatal piglets undergoing deep hypothermic circulatory arrest

Faraz Kerendi, MD a , Michael E. Halkos, MD a , Hajime Kin, MD a , Joel S. Corvera, MD a , Daniel J. Brat, MD, PhD b , Mary B. Wagner, PhD c , Jakob Vinten-Johansen, PhD a , Zhi-Qing Zhao, PhD a , Joseph M. Forbess, MD a , Kirk R. Kanter, MD a , Mary E. Kelley, PhD d , Paul M. Kirshbom, MD a , *

a Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Ga
b Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Ga
c Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga
d Department of Biostatistics, Emory University School of Medicine, Atlanta, Ga

Received for publication March 10, 2005; revisions received May 1, 2005; accepted for publication May 5, 2005.

* Address for reprints: Paul M. Kirshbom, MD, Cardiothoracic Surgery, Emory Clinic, Building A, 1365 Clifton Rd, NE, Atlanta, GA 30322 (Email: paul_kirshbom{at}emoryhealthcare.org).

BACKGROUND: Prolonged deep hypothermic circulatory arrest is known to cause neurological injury. Hypoxia inducible factor, a transcription factor that mediates adaptive changes during hypoxia, is neuroprotective in models of ischemic brain injury, in part by upregulating erythropoietin. This study tested the hypothesis that upregulation of hypoxia inducible factor and erythropoietin by preconditioning with hypoxia or the hypoxia-mimetic agents deferoxamine and cobalt chloride would be neuroprotective in a piglet model of deep hypothermic circulatory arrest.

METHODS: Anesthetized neonatal piglets were randomized to 4 preconditioning groups (15 per group): hypoxia, deferoxamine, cobalt chloride, or control (NaCl vehicle). Brain hypoxia inducible factor and erythropoietin contents were assessed by means of Western blotting at 3, 8, and 24 hours after treatment (n = 3 per time point). Twenty-four hours after treatment, 6 to 7 animals per group underwent cardiopulmonary bypass and 110 minutes of deep hypothermic circulatory arrest. After recovery, serial neurobehavioral examinations were conducted for 6 days, after which histopathologic brain injury and neuronal apoptosis (cleaved caspase 3) were assessed.

RESULTS: Erythropoietin expression was not significantly increased by any of the pretreatment strategies. In contrast, there was a significant upregulation of hypoxia inducible factor by pretreatment with deferoxamine and cobalt chloride (P = .002). Neurobehavioral measures revealed no significant differences in time to recovery or extent of injury. Examination of histopathologic brain injury in the hippocampus revealed that pretreatment with deferoxamine (0.4 ± 0.3) and cobalt chloride (0.5 ± 0.3) were associated with significantly less neuronal loss than pretreatment with hypoxia or control (2.8 ± 0.5, P = .004). Finally, cleaved caspase 3 (a marker of apoptotic cell death) was also shown to be diminished in the cobalt and deferoxamine groups, but the difference was not significantly different from the value in the control group.

CONCLUSIONS: In contrast to hypoxia, deferoxamine and cobalt chloride preconditioning upregulated hypoxia inducible factor and were associated with histopathologic neuroprotection after exposure to cardiopulmonary bypass and prolonged deep hypothermic circulatory arrest.

19; 25; 29




This article has been cited by other articles:


Home page
 J. Thorac. Cardiovasc. Surg.Home page
E. J. Hickey, X. You, V. Kaimaktchiev, M. Stenzel-Poore, and R. M. Ungerleider
Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest
J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1588 - 1596.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
A. M. Sheikh, C. Barrett, N. Villamizar, O. Alzate, S. Miller, J. Shelburne, A. Lodge, J. Lawson, and J. Jaggers
Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with deep hypothermic circulatory arrest
J. Thorac. Cardiovasc. Surg., October 1, 2006; 132(4): 820 - 828.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
F. Kerendi, P. M. Kirshbom, M. E. Halkos, N.-P. Wang, H. Kin, R. Jiang, Z.-Q. Zhao, K. R. Kanter, R. A. Guyton, and J. Vinten-Johansen
Cobalt Chloride Pretreatment Attenuates Myocardial Apoptosis After Hypothermic Circulatory Arrest
Ann. Thorac. Surg., June 1, 2006; 81(6): 2055 - 2062.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2005 by The American Association for Thoracic Surgery.