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

^a Department of Surgery, The University of California – San Diego, San Diego, CA, United States
^b Department of Anesthesiology & Critical Care, Children's Hospital of Philadelphia, Philadelphia, PA, United States
^c Department of Biochemistry & Biophysics, The University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, United States
^d Department of Anesthesiology & Critical Care, Mayo Clinic, Rochester, MN, United States

Received 2 September 2008; received in revised form 1 January 2009; accepted 3 January 2009.

^_* Corresponding author. Address: Rady Children's Hospital/The University of California, San Diego, 3030 Children's Way, Suite 202, San Diego, CA 92123, United States. Tel.: +1 858 966 8030; fax: +1 858 966 8032. (Email: ppastuszko{at}rchsd.org).

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 30 min of DHCA followed by 1 h of low flow at 20 ml/kg/min, rewarmed to 37 °C (normothermia) or to 33 °C (hypothermia), separated from CPB, and monitored for 6 h. 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. 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.

Key Words: Newborn • Brain • Cardiopulmonary bypass • Circulatory arrest • Hypothermia • Apoptosis

This article has been cited by other articles:

				M. Sakurai Which cell does apoptosis induce? Eur. J. Cardiothorac. Surg., October 1, 2009; 36(4): 782 - 782. [Full Text] [PDF]

				P. Pastuszko, W. J. Greeley, D. F. Wilson, and A. Pastuszko Reply to Sakurai. Brain injury in cardiopulmonary bypass surgery Eur. J. Cardiothorac. Surg., October 1, 2009; 36(4): 782 - 783. [Full Text] [PDF]