The excitatory amino antagonist
MK-801 was administered to cats following
resuscitation from
cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete
cerebral ischemia. In 29 cats studied,
cardiac arrest (
ventricular fibrillation) was maintained for 18 min and
resuscitation was successfully performed in 21 cats. Four animals underwent a
sham arrest.
MK-801 or placebo was administered in a blinded, randomized manner. Beginning at 5 min post
resuscitation (PR),
MK-801 330 micrograms/kg over 2 min followed by 73 micrograms/kg/h for 10 h or the same volume of placebo was administered. Resuscitated animals remained paralyzed and sedated in an
intensive care setting for 24-30 h PR. Neurologic examinations were performed at 2, 4, and 7 days PR by observers blinded to the treatment groups. Seventeen cats were entered into data analysis (nine
MK-801-treated and eight placebo-treated). MK-801-treated animals had a significantly greater
neurologic deficit score (
NDS) rank (0 = normal, 100 =
brain death) 2 days PR (mean rank 12.1 vs. 5.6; p = 0.008). This difference is most likely due to ongoing
sedative actions of
MK-801. There were no significant differences in
NDS rank at 4 (10.3,
MK-801 vs. 7.5, placebo) and 7 (9.6,
MK-801 vs. 8.3, placebo) days PR. There were no significant differences in frontal cortex, hippocampus, occipital cortex, or cerebellar neuropathology between groups.
Sham-arrested cats had normal neurologic and neuropathologic evaluations. In the circumstance of complete
cerebral ischemia as employed in the current study,
MK-801 had no beneficial effect upon neurologic or neuropathologic outcome.