title: Hypothermic circulatory arrest increases permeability of the blood brain barrier in watershed areas.
abstract: 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.
authors.affiliation: Children's National Heart Institute, Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Okamura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ishibashi
authors.forename: T Susheel
authors.initials: TS
authors.lastname: Kumar
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.forename: Hart G W
authors.initials: HG
authors.lastname: Lidov
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jonas
mesh_terms: D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005070:Evans Blue / Q000493:pharmacokinetics*; D010539:Permeability; D012307:Risk Factors; D013552:Swine
chemical_list: D004396:Coloring Agents; D005070:Evans Blue