Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain.

Luca Centola, Hitoshi Kanamitsu, Katsushi Kinouchi, Yasuhiro Fuji, Hiroki Ito, Katsuhide Maeda, Roland Beckman, Xiaoyuan Ma, Frank L Hanley, Robert Kirk Riemer

The Annals of thoracic surgery 2020 Dec

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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. Neonatal pigs (7 days old) undergoing bypass were assigned to 4 groups: DHCA at 18°C and ACP at 18°, 25°, and 32° for 45 minutes (n = 6 per group). ACP was initiated through the innominate artery and maintained at 40 mL/kg/min. After bypass, all animals were maintained sedated and intubated for 24 hours before being euthanized. Brain subventricular zone tissues were analyzed for histologic injury by assessing apoptosis and neural homeostasis (Nestin). Histologic examination showed no significant ischemic/hypoxic neuronal death at any cooling temperature among the 4 treatment groups. However, we detected a significantly higher apoptotic rate in DHCA compared with ACP at 18°C (P = .003-.017) or 25°C (P = .012-.043), whereas apoptosis at 32°C was not different from DHCA. Of note, we identified increased Nestin expression in the DHCA group compared with all ACP groups (P range = .011-.041). Neonatal piglet ACP at 18° 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. Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Citation

Luca Centola, Hitoshi Kanamitsu, Katsushi Kinouchi, Yasuhiro Fuji, Hiroki Ito, Katsuhide Maeda, Roland Beckman, Xiaoyuan Ma, Frank L Hanley, Robert Kirk Riemer. Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain. The Annals of thoracic surgery. 2020 Dec;110(6):2076-2081