Hypothermic Circulatory Arrest increases Permeability of Blood Brain Barrier in Watershed Area

  • Toru Okamura, Cardiac Surgery, Children’s National Heart Institute, Children’s National Medical Center, United States
  • Nobuyuki Ishibashi, Cardiac Surgery, Children’s National Heart Institute, Children’s National Medical Center, United States
  • TK Susheel, Cardiac Surgery, Children’s National Heart Institute, Children’s National Medical Center, United States
  • David Zurakowski, Cardiac Surgery, Children’s National Heart Institute, Children’s National Medical Center, United States
  • Richard Jonas, Cardiac Surgery, Children’s National Heart Institute, Children’s National Medical Center, United States

    • Objective: The integrity of blood brain barrier (BBB) after cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) is controversial, especially in children. We tested the hypothesis that BBB is disrupted by HCA.

    Methods: 25 piglets (mean weight 12kg) were randomly assigned to 5 groups (5 per group): anesthesia alone (control); CPB at 37°C with full-flow (FF); CPB at 25°C with very low flow (LF) and HCA at15 or 25°C. Evans blue dye was infused two hours after end of CPB. Brain was removed after one hour observation. Evans Blue (EB) extravasation in brain tissue was measured using the following two methods; 1) extraction method of EB with homogenate for cortex and cerebellum; ratio of EB of brain tissue /plasma was compared in all groups and 2) imaging methods; i) macroscopic method for whole brain and ii) microscopic method with immunohistochemistry for cortex, caudate nucleus, thalamus, hippocampus and cerebellum using measuring density of EB.

    Results: 1) The quantity of EB in cortex and cerebellum was significantly higher in 25°C HCA than control. 2-i) BBB disruption was obvious macroscopically around watershed areas in 25°C HCA. 2-ii) Microscopic data showed that the leakage of EB in 25°C HCA was significantly more severe than control in the cortex, caudate nucleus, thalamus, hippocampus and cerebellum. (p<.05)

    Conclusions: BBB is impaired around watershed areas by 25°C HCA for one hour. 15°C HCA and 25°C LF were more effective in maintaining BBB integrity than 25°C HCA. Images data show clear evidence of BBB leakages in 25°C HCA.