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

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.

An in vitro study of the effectiveness of carbon dioxide flushing of arterial line filters.

Gaseous microemboli (GMEs) have been connected to neurologic impairment and other ischemic complications after surgery. The components of the extracorporeal circuit (ECC) have a large influence on GME production. This in vitro study investigates the use of carbon dioxide flushing of the 38-microm Medtronic Affinity CB351 and 38-microm Medtronic Affinity 351 arterial line filters (ALFs) to decrease GMEs and time for air to clear the ALE An adult circuit was implemented with a silicone oxygenator for vacuum-assisted gas removal and to reduce air before ALE The 48 filters were separated into four equal groups: flushed coated and non-coated and non-flushed coated and non-coated. Carbon dioxide flushing was performed at 6 L/min for 3 minutes. ALFs were retrograde primed at 200 mL/min. An Emboli Detection and Classification Quantifier (EDAC) was used to gather data. The average total emboli and time to clear (seconds) for flush coated were 20.25 +/- 16.78 and 142.17 +/- 174.80 seconds, respectively, flushed non-coated were 30.5 +/- 34.65 and 124.17 +/- 131.40 seconds, non-flushed coated were 162.08 +/- 79.90 and 390.42 +/- 84.36 seconds, and non-flushed non-coated were 163.67 +/- 212.67 and 305.92 +/- 179.36 seconds. Flushed filters had an average total emboli count of 25.375 +/- 27.14 and an average time to clear of 13.167 +/- 151.51 seconds. Non-flushed filters had an average total emboli count of 162.875 +/- 157.11 and an average time to clear of 348.167 +/- 143.70 seconds. Coated and non-coated filters for total emboli and time to clear had p values of .86 and .24, respectively. Flushed and non-flushed filters had total emboli and time to clear p values of < .001 and < .001, respectively. No significant difference was found between coated and non-coated filters involving total embolic count and time to clear. A significant difference was found in total embolic count and time to clear between flushed and non-flushed filters. This study shows that fewer emboli and faster embolic clearance time correlate with carbon dioxide flushing of the ALE.