The effect of hypothermia on neuronal viability following cardiopulmonary bypass and circulatory arrest in newborn piglets.
OBJECTIVE
To determine the effect of recovery with mild hypothermia after cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on the activity of selected key proteins involved in initiation (Bax, Caspase-3) or inhibition of apoptotic injury (Bcl-2, increased ratio Bcl-2/Bax) in the brain of newborn piglets.


METHODS
The piglets were placed on CPB, cooled with pH-stat management to 18 degrees C, subjected to 30 min of DHCA followed by 1h of low flow at 20 ml/kg/min, rewarmed to 37 degrees C (normothermia) or to 33 degrees C (hypothermia), separated from CPB, and monitored for 6h. Expression of above proteins was measured in striatum, hippocampus and frontal cortex by Western blots. The results are mean for six experiments+/-SEM.


RESULTS
There were no significant differences in Bcl-2 level between normothermic and hypothermic groups. The Bax levels in normothermic group in cortex, hippocampus and striatum were 94+/-9, 136+/-22 and 125+/-34 and decreased in the hypothermic group to 59+/-17 (p=0.028), 70+/-6 (p=0.002) and 48+/-8 (p=0.01). In cortex, hippocampus and striatum Bcl-2/Bax ratio increased from 1.23, 0.79 and 0.88 in normothermia to 1.96, 1.28 and 2.92 in hypothermia. Expression of Caspase-3 was 245+/-39, 202+/-74 and 244+/-31 in cortex, hippocampus and striatum in the normothermic group and this decreased to 146+/-24 (p=0.018), 44+/-16 (p=7 x 10(-7)) and 81+/-16 (p=0.01) in the hypothermic group.


CONCLUSIONS
In neonatal piglet model of cardiopulmonary bypass with circulatory arrest, mild hypothermia during post bypass recovery provides significant protection from cellular apoptosis, as indicated by lower expression of Bax and Caspase-3 and an increased Bcl-2/Bax ratio. The biggest protection was observed in striatum probably by decreasing of neurotoxicity of striatal dopamine.
Pastuszko
Peter
P
Department of Surgery, The University of California - San Diego, San Diego, CA, USA.
Pirzadeh
Afsaneh
A
Reade
Erin
E
Kubin
Joanna
J
Mendoza
Alberto
A
Schears
Gregory J
GJ
Greeley
William J
WJ
Pastuszko
Anna
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D053148:Caspase 3 / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D006324:Heart Arrest, Induced / Q000379:methods*; D007036:Hypothermia, Induced; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034421:Sus scrofa; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3