Improving neurological outcomes post-cardiac arrest in a rat model: immediate hypothermia and quantitative EEG monitoring.
OBJECTIVE
Therapeutic hypothermia (TH) after cardiac arrest (CA) improves outcomes in a fraction of patients. To enhance the administration of TH, we studied brain electrophysiological monitoring in determining the benefit of early initiation of TH compared to conventional administration in a rat model.


METHODS
Using an asphyxial CA model, we compared the benefit of immediate hypothermia (IH, T=33 degrees C, immediately post-resuscitation, maintained 6h) to conventional hypothermia (CH, T=33 degrees C, starting 1h post-resuscitation, maintained 12h) via surface cooling. We tracked quantitative EEG using relative entropy (qEEG) with outcome verification by serial Neurological Deficit Score (NDS) and quantitative brain histopathological damage scoring (HDS). Thirty-two rats were divided into 4 groups based on CH/IH and 7/9-min duration of asphyxial CA. Four sham rats were included for evaluation of the effect of hypothermia on qEEG.


RESULTS
The 72-h NDS of the IH group was significantly better than the CH group for both 7-min (74/63; median, IH/CH, p<0.001) and 9-min (54/47, p=0.022) groups. qEEG showed greater recovery with IH (p<0.001) and significantly less neuronal cortical injury by HDS (IH: 18.9+/-2.5% versus CH: 33.2+/-4.4%, p=0.006). The 1-h post-resuscitation qEEG correlated well with 72-h NDS (p<0.05) and 72-h behavioral subgroup of NDS (p<0.01). No differences in qEEG were noted in the sham group.


CONCLUSIONS
Immediate but shorter hypothermia compared to CH leads to better functional outcome in rats after 7- and 9-min CA. The beneficial effect of IH was readily detected by neuro-electrophysiological monitoring and histological changes supported the value of this observation.
Jia
Xiaofeng
X
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. xjia1@jhmi.edu
Koenig
Matthew A
MA
Shin
Hyun-Chool
HC
Zhen
Gehua
G
Pardo
Carlos A
CA
Hanley
Daniel F
DF
Thakor
Nitish V
NV
Geocadin
Romergryko G
RG
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000517:prevention & control; D016887:Cardiopulmonary Resuscitation; D004569:Electroencephalography; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013997:Time Factors