TY - JOUR
T1 - Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain
AU - Centola, Luca
AU - Kanamitsu, Hitoshi
AU - Kinouchi, Katsushi
AU - Fuji, Yasuhiro
AU - Ito, Hiroki
AU - Maeda, Katsuhide
AU - Beckman, Roland
AU - Ma, Xiaoyuan
AU - Hanley, Frank L.
AU - Riemer, Robert Kirk
N1 - Funding Information:
This research was funded through support from the Congenital Cardiac Division of the Department of Cardiothoracic Surgery directed to Dr Frank L. Hanley.
Publisher Copyright:
© 2020 The Society of Thoracic Surgeons
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Background: 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. Methods: 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). Results: 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). Conclusions: 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.
AB - Background: 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. Methods: 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). Results: 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). Conclusions: 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.
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U2 - 10.1016/j.athoracsur.2020.02.058
DO - 10.1016/j.athoracsur.2020.02.058
M3 - Article
C2 - 32240645
AN - SCOPUS:85084753105
VL - 110
SP - 2076
EP - 2081
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
SN - 0003-4975
IS - 6
ER -