Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets.
OBJECTIVE
Cardiac 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, alpha-aminoisobutyric 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.


RESULTS
The mean +/- SEM of the transfer coefficient of alpha-aminoisobutyric acid in cerebrum was (in microL/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.


CONCLUSIONS
Pretreatment 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.
Schleien
C L
CL
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD.
Eberle
B
B
Shaffner
D H
DH
Koehler
R C
RC
Traystman
R J
RJ
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D016887:Cardiopulmonary Resuscitation; D002374:Catalase / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D016166:Free Radical Scavengers; D006323:Heart Arrest / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012016:Reference Values; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors
D000621:Aminoisobutyric Acids; D016166:Free Radical Scavengers; C070295:catalase-polyethylene glycol; C100049:2-aminoisobutyric acid; D011092:Polyethylene Glycols; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D004837:Epinephrine