Abstract 11450: Deep Hypothermic Circulatory Arrest Activation of Neural Precursor Cells in Neonatal Brain Subventricular Zone is Prevented by Antegrade Cerebral Perfusion

IntroductionThe use of Antegrade Cerebral Perfusion (ACP) as an alternative to Deep Hypothermic Circulatory Arrest (DHCA) in the setting of CPB as a neuroprotection strategy in neonates has become a common approach, although the value of ACP over DHCA remains highly debated.HypothesisDHCA induces a profoundly different disruption to neonatal brain homeostasis that does not occur when ACP is used.MethodsTwenty-four 7-day old neonatal piglets undergoing cardiopulmonary bypass (CPB) with the initial flow rate of 200 mL/kg/min were assigned to four groupsDHCA at 18°C and ACP at 18°C, 25°C and 32°C for 45 minutes (n= 6/ group). ACP was started via innominate artery and maintained at a fixed flow rate (40 ml/kg/min). All animals were kept sedated and intubated for 24 hours before being euthanized. Brain Subventricular zone (SVZ) tissues were analyzed for histological injuryH&E, apoptosis (TUNEL), and neural homeostasis (Nestin), and data were compared using ANOVA with post hoc analysis.ResultsHistological examination of the four treatment groups showed no significant evidence of ischemic/hypoxic neuronal death at any cooling temperature in the whole brain. However, TUNEL Immunostaining in SVZ revealed a significantly lower apoptotic rate in ACP 18 and ACP 25 groups (p0.05). Of note however, we identified increased SVZ Nestin expression in the DHCA group compared to all ACP temperature groups (p=0.032).ConclusionsIn the neonatal piglet Antegrade Cerebral Perfusion at 18°C or 25°C provides adequate protection from increased brain cellular apoptosis. Furthermore, in contrast to ACP, DHCA induces Nestin expression, indicating the activation of neural progenitor cells and the potential of altering the neonatal neurodevelopment process. DHCA has the potential to more profoundly disrupt neural homeostasis than does ACP.