Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets

Background and PurposeCardiac arrest and resuscitation in immature piglets result in a delayed increase in blood-brain barrier permeability. We tested the hypothesis that pretreatment with oxygen radical scavengers reduces postischemic permeability. Methods Permeability was assessed by measuring the plasma-to-brain transfer coefficient of the small amino acid, a-ami-noisobutyric acid, in 2- to 3-week-old anesthetized piglets. Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n=8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10 000 U/kg) and to catalase (20 000 U/kg). The ischemia protocol consisted of 8 minutes of ventricular fibrillation, 6 minutes of cardiopulmonary resuscitation, defibrillation, and 4 hours of spontaneous circulation. ResultsThe mean±SEM of the transfer coefficient of α-aminoisobutyric acid in cerebrum was (in μL/g per minute): 1.54 ± 0.37 in the nonischemic group, 2.04 ± 0.26 in the ischemia group treated with vehicle, and 1.29 ± 0.25 in the ischemia group treated with oxygen radical scavengers. Postischemic values with scavenger treatment were significantly lower than those with vehicle treatment in cerebrum, cerebellum, medulla, and cervical spinal cord. ConclusionsPretreatment with oxygen radical scavengers reduces postischemic blood-brain barrier permeability by a small amino acid. These data are consistent with oxygen radical-mediated dysfunction of cerebral endothelium in a pediatric model of cardiopulmonary resuscitation.