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Updated: Jun 6, 2026

Establishment of Deep Hypothermic Circulatory Arrest in Rats
Published on: December 16, 2022
Hypothermic circulatory arrest increases permeability of the blood brain barrier in watershed areas
Toru Okamura1, Nobuyuki Ishibashi, T Susheel Kumar
1Children's National Heart Institute, Children's National Medical Center, Washington, DC 20010, USA.
Insights
Hypothermic circulatory arrest (HCA) at 25°C impairs the blood-brain barrier (BBB) in piglets, particularly in watershed areas. This BBB disruption may contribute to brain damage following cardiopulmonary bypass (CPB).
Area of Science:
- Cardiovascular Surgery
- Pediatric Surgery
- Neuroscience
Background:
- The integrity of the blood-brain barrier (BBB) following cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) in pediatric patients remains a subject of debate.
- This study investigated the impact of HCA on BBB integrity.
Purpose of the Study:
- To test the hypothesis that HCA disrupts the BBB.
- To evaluate the effect of different HCA temperatures on BBB integrity.
Main Methods:
- Forty-one piglets underwent acute and survival studies involving CPB with varying temperatures and flow rates, including HCA at 15°C and 25°C.
- Blood-brain barrier integrity was assessed using Evans blue dye (EBD) extravasation and immunohistochemical analysis of albumin.
- Cerebral histology was evaluated in survival studies.
Main Results:
- Significant BBB disruption was observed around watershed areas in piglets subjected to HCA at 25°C.
- Microscopic analysis confirmed more severe EBD leakage and albumin extravasation in the 25°C HCA group compared to controls.
- Histologic damage scores were elevated in watershed areas following 25°C HCA.
Conclusions:
- HCA at 25°C for 1 hour impairs the BBB around watershed areas, as evidenced by both macroscopic and microscopic findings.
- Increased BBB permeability is suggested to be both an indicator and a contributing factor to brain damage.
Background:
The integrity of the blood brain barrier (BBB) after cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) is controversial in children. We tested the hypothesis that the BBB is disrupted by HCA.
Methods:
Forty-one piglets (mean weight 11 kg) were randomly allocated to acute and survival experiments. Five groups (25 piglets, 5 per group) underwent acute studies: anesthesia alone (control); CPB at 37°C with full-flow (FF); CPB at 25°C with very low flow (LF); HCA at 15°C, and HCA at 25°C. Two groups (16 piglets, 8 per group) underwent survival studies: CPB at 25°C with LF and HCA. In the acute studies, Evans blue dye (EBD) extravasation through the BBB into the brain was measured using two methods: EBD absorbance of homogenized brain, and immunohistochemical localization of EBD-linked albumin for cortex, caudate nucleus, thalamus, hippocampus, and cerebellum. In the survival studies, cerebral histology was assessed with hematoxylin-eosin stain after sacrifice at 4 days after surgery.
Results:
The BBB disruption was clearly observed around watershed areas for 25°C HCA compared with other conditions. Microscopic data showed that leakage of EBD in 25°C HCA was more severe than control in all brain areas (p < 0.05), and EBD and albumin were colocalizing. Histologic damage scores were significantly higher in watershed areas with 25°C HCA.
Conclusions:
The BBB was impaired around watershed areas by 25°C HCA for 1 hour according to both macroscopic and microscopic data. An increase in permeability of the BBB may be both a sign and a mechanism of brain damage.
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