Document Detail


Noninvasive assessment of brain injury in a canine model of hypothermic circulatory arrest using magnetic resonance spectroscopy.
MedLine Citation:
PMID:  16631640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Studies have confirmed the neuroprotective effect of diazoxide in canines undergoing hypothermic circulatory arrest (HCA). A decreased N-acetyl-asparate:choline (NAA:Cho) ratio is believed to reflect the severity of neurologic injury. We demonstrated that noninvasive measurement of NAA:Cho with magnetic resonance spectroscopy facilitates assessment of neuronal injury after HCA and allows for evaluation of neuroprotective strategies. METHODS: Canines underwent 2 hours of HCA at 18 degrees C and were observed for 24 hours. Animals were divided into three groups (n = 15 in each group): normal (unoperated), HCA (HCA only), and HCA+diazoxide (pharmacologic treatment before HCA). The NAA:Cho ratios were obtained 24 hours after HCA by spectroscopy. Brains were immediately harvested for fresh tissue NAA quantification by mass spectrometry. Separate cohorts of HCA (n = 16) and HCA+diazoxide (n = 23) animals were kept alive for 72 hours for daily neurologic assessment. RESULTS: Cortical NAA:Cho ratios were significantly decreased in HCA versus normal animals (1.01 +/- 0.29 versus 1.31 +/- 0.23; p = 0.004), consistent with severe neurologic injury. Diazoxide pretreatment limited neurologic injury versus HCA alone, reflected in a preserved NAA:Cho ratio (1.21 +/- 0.27 versus 1.01 +/- 0.29; p = 0.05). Data were substantiated with fresh tissue NAA extraction. A significant decrease in cortical NAA was observed in HCA versus normal (7.07 +/- 1.9 versus 8.54 +/- 2.1 micromol/g; p = 0.05), with maintenance of normal NAA levels after diazoxide pretreatment (9.49 +/- 1.1 versus 7.07 +/- 1.9 micromol/g; p = 0.0002). Clinical neurologic scores were significantly improved in the HCA+diazoxide group versus HCA at all time points. CONCLUSIONS: Neurologic injury remains a significant complication of cardiac surgery and is most severe after HCA. Magnetic resonance spectroscopy assessment of NAA:Cho ratios offers an early, noninvasive means of potentially evaluating neurologic injury and the effect of neuroprotective agents.
Authors:
Christopher J Barreiro; Jason A Williams; Torin P Fitton; Mary S Lange; Mary E Blue; Lisa Kratz; Peter B Barker; Mahaveer Degaonkar; Vincent L Gott; Juan C Troncoso; Michael V Johnston; William A Baumgartner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  81     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-24     Completed Date:  2006-05-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1593-8     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiac Surgery, Kennedy-Krieger Research Institute, Baltimore, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartic Acid / analogs & derivatives,  metabolism
Cardiopulmonary Bypass
Cerebellum / metabolism
Cerebral Cortex / metabolism
Choline / metabolism
Circulatory Arrest, Deep Hypothermia Induced*
Diazoxide / therapeutic use
Dogs
Hippocampus / metabolism
Hypoxia, Brain / diagnosis*,  metabolism
Magnetic Resonance Spectroscopy*
Male
Models, Animal
Neurons / pathology
Neuropsychological Tests
Vasodilator Agents / therapeutic use
Grant Support
ID/Acronym/Agency:
R37NS31238-10/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Vasodilator Agents; 364-98-7/Diazoxide; 56-84-8/Aspartic Acid; 62-49-7/Choline; 997-55-7/N-acetylaspartate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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