Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in Neonatal Brain

Use of Antegrade Cerebral Perfusion (ACP) as an alternative neuroprotection strategy to Deep Hypothermic Circulatory Arrest (DHCA) in the setting of cardiopulmonary bypass in neonates has become a common approach, although the value of ACP over DHCA remains highly debated. This study investigated the disruption to neonatal brain homeostasis by DHCA and ACP.

Seven-day old neonatal piglets undergoing bypass were assigned to four groups: DHCA at 18°C and ACP at 18, 25 and 32°C for 45 minutes (n= 6/ group). ACP was initiated via innominate artery and maintained at (40 ml/kg/min). Following bypass, all animals were maintained sedated and intubated for 24 hours before being euthanized. Brain subventricular zone tissues were analyzed for histological injury: apoptosis, and neural homeostasis (Nestin).

Histological examination showed no significant ischemic/hypoxic neuronal death at any cooling temperature among all four treatment groups. However, we detected a significantly higher apoptotic rate in DHCA compared to ACP18°C (p range 0.003 to 0.017) or ACP25°C (p range 0.012 to 0.043), while apoptosis at ACP32°C was not different from DHCA. Of note, we identified increased Nestin expression in the DHCA group compared to all ACP groups (p range = 0.011 – 0.041).

Neonatal piglet ACP at 18°C or 25°C provides adequate protection from increased brain cellular apoptosis. In contrast to ACP however, DHCA induces brain Nestin expression, indicating activation of neural progenitor cells and the potential of altering neonatal neurodevelopmental progression. DHCA has potential to more profoundly disrupt neural homeostasis than does ACP.