The effect of hypothermia on neuronal viability following cardiopulmonary bypass and circulatory arrest in newborn piglets

Pastuszko, Peter; Pirzadeh, Afsaneh; Reade, Erin; Kubin, Joanna; Mendoza, Alberto; Schears, Gregory J.; Greeley, William J.; Pastuszko, Anna
April 2009
European Journal of Cardio-Thoracic Surgery;Apr2009, Vol. 35 Issue 4, p577
Academic Journal
Abstract: 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°C, subjected to 30min of DHCA followed by 1h of low flow at 20ml/kg/min, rewarmed to 37°C (normothermia) or to 33°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 =7×10−7) and 81±16 (p =0.01) in the hypothermic group. Conclusion: 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.


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