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Christopher J. Barreiro
Jason A. Williams
Torin P. Fitton
Vincent L. Gott
Michael V. Johnston
William A. Baumgartner
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Right arrow Cerebral protection

Ann Thorac Surg 2006;81:1593-1598
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Noninvasive Assessment of Brain Injury in a Canine Model of Hypothermic Circulatory Arrest Using Magnetic Resonance Spectroscopy

Christopher J. Barreiro, MD a , b , c , d , Jason A. Williams, MD a , b , c , d , Torin P. Fitton, MD a , b , c , d , Mary S. Lange, MA a , b , c , d , Mary E. Blue, PhD a , b , c , d , Lisa Kratz, PhD a , b , c , d , Peter B. Barker, PhD a , b , c , d , Mahaveer Degaonkar, PhD a , b , c , d , Vincent L. Gott, MD a , b , c , d , Juan C. Troncoso, MD a , b , c , d , Michael V. Johnston, MD a , b , c , d , William A. Baumgartner, MD a , b , c , d , *

a Division of Cardiac Surgery, Kennedy-Krieger Research Institute, Baltimore, Maryland
b Division of Neurology, Kennedy-Krieger Research Institute, Baltimore, Maryland
c Division of Neuropathology, Kennedy-Krieger Research Institute, Baltimore, Maryland
d Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Accepted for publication January 4, 2006.

* Address correspondence to Dr Baumgartner, Division of Cardiac Surgery, The Johns Hopkins Medical Institutions, 600 North Wolfe St, Blalock 618, Baltimore, MD 21287 (Email: wbaumgar{at}csurg.jhmi.jhu.edu).

Presented at the Poster Session of the Fifty-second Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 10–12, 2005.

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°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 µmol/g; p = 0.05), with maintenance of normal NAA levels after diazoxide pretreatment (9.49 ± 1.1 versus 7.07 ± 1.9 µmol/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.




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