Mild hypothermia induced before cardiac arrest reduces brain edema formation in rats.
OBJECTIVE
The mechanisms by which hypothermia improves cardiac arrest (CA)-induced brain damage are unclear. The authors hypothesized that mild hypothermia induced before CA attenuates brain edema formation by preventing neutrophil-mediated dysfunction of the endothelial cell junction proteins.


METHODS
Eighteen rats were randomized to normal control surgery (group 1, n = 6), normothermic (37.5 degrees C) CA (group 2, n = 6), or hypothermic (34 degrees C) CA (group 3, n = 6). Hypothermia was induced with external cooling before CA in group 3. Cardiac arrest was induced by 8 minutes of asphyxiation. Brain edema was determined by wet-to-dry weight ratio and cerebral spinal fluid pressure (CSFP). Brain neutrophil content was determined by myeloperoxidase (MPO) activity, and occludin degradation was assessed by western blotting.


RESULTS
Normothermic CA significantly increased brain wet-to-dry weight ratio from 4.52 +/- 0.04 in group 1 to 4.80 +/- 0.04 in group 2 (p = 0.0003) and CSFP from 3.6 +/- 0.9 in group 1 to 8.9 +/- 0.9 mm Hg in group 2 (p = 0.004). Mild hypothermia before CA in group 3 significantly reduced brain wet-to-dry weight ratio (4.68 +/- 0.03, p = 0.008 vs. group 2) and CSFP (3.8 +/- 0.5 mm Hg, p = 0.004 vs. group 2). Cardiac arrest increased brain MPO from 0.07 +/- 0.025 in group 1 to 0.16 +/- 0.02 units/gram brain weight in group 2 (p = 0.006) that was not decreased by hypothermia before CA (0.12 +/- 0.02 in group 3 (p = 0.07 vs. group 2). There was no occludin proteolysis in any group.


CONCLUSIONS
Mild hypothermia before CA decreases CA-induced brain edema. The hypothermia-elicited reduction in brain edema does not appear to be neutrophil-dependent and the early brain edema formation may not involve the proteolysis of occludin.
Xiao
Feng
F
Department of Emergency Medicine, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. fxiao@ems.lsuhsc.edu
Zhang
Shu
S
Arnold
Thomas C
TC
Alexander
J Steven
JS
Huang
Jian
J
Carden
Donna L
DL
Conrad
Steven A
SA
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D001929:Brain Edema / Q000503:physiopathology / Q000517:prevention & control*; D006323:Heart Arrest / Q000503:physiopathology / Q000628:therapy*; D007036:Hypothermia, Induced; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D062793:Occludin; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D009195:Peroxidase