TY - JOUR
T1 - Noninvasive Assessment of Brain Injury in a Canine Model of Hypothermic Circulatory Arrest Using Magnetic Resonance Spectroscopy
AU - Barreiro, Christopher J.
AU - Williams, Jason A.
AU - Fitton, Torin P.
AU - Lange, Mary S.
AU - Blue, Mary E.
AU - Kratz, Lisa
AU - Barker, Peter B.
AU - Degaonkar, Mahaveer
AU - Gott, Vincent L.
AU - Troncoso, Juan C.
AU - Johnston, Michael V.
AU - Baumgartner, William A.
N1 - Funding Information:
This study was supported by the Dana and Albert Broccoli Center for Aortic Diseases, the Mildred and Carmont Blitz Cardiac Research Fund, and the National Institutes of Health (NIH R37[NS31238-10], William A. Baumgartner-PI). Doctor Christopher Barreiro is a Hugh R. Sharp, Jr, Research Fellow, and Drs Jason Williams and Torin Fitton are Irene Piccinini Investigators. Doctor William Baumgartner is the Vincent L. Gott Professor of Cardiac Surgery. The authors would also like to thank Melissa Jones, Jeffrey Brawn, and Tamara Treat for their contribution of outstanding technical assistance. This project could not have been completed without their participation.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/33646840633
U2 - 10.1016/j.athoracsur.2006.01.011
DO - 10.1016/j.athoracsur.2006.01.011
M3 - Article
C2 - 16631640
AN - SCOPUS:33646840633
SN - 0003-4975
VL - 81
SP - 1593
EP - 1598
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 5
ER -