Noninvasive assessment of brain injury in a canine model of hypothermic circulatory arrest using magnetic resonance spectroscopy.
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.
Barreiro
Christopher J
CJ
Division of Cardiac Surgery, Kennedy-Krieger Research Institute, Baltimore, Maryland, USA.
Williams
Jason A
JA
Fitton
Torin P
TP
Lange
Mary S
MS
Blue
Mary E
ME
Kratz
Lisa
L
Barker
Peter B
PB
Degaonkar
Mahaveer
M
Gott
Vincent L
VL
Troncoso
Juan C
JC
Johnston
Michael V
MV
Baumgartner
William A
WA
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D050792:Circulatory Arrest, Deep Hypothermia Induced; D003981:Diazoxide / Q000627:therapeutic use; D004285:Dogs; D006624:Hippocampus / Q000378:metabolism; D002534:Hypoxia, Brain / Q000175:diagnosis* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000473:pathology; D009483:Neuropsychological Tests; D014665:Vasodilator Agents / Q000627:therapeutic use
D014665:Vasodilator Agents; D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline; D003981:Diazoxide