Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a study in a chronic porcine model.
BACKGROUND
Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present studies was to determine the potential efficacy of lamotrigine, an Na(+) channel blocker, to mitigate cerebral injury after hypothermic circulatory arrest.


METHODS
Sixteen pigs (21-27 kg) were randomly assigned to receive lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest (20 degrees C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100beta protein was determined up to the first postoperative morning. Daily behavioral assessment was performed until the animal died or was put to death on day 7. Histologic analysis of the brain was carried out in all animals.


RESULTS
Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8 vs 7, P =.02). The medians of recovered electroencephalographic bursts in the lamotrigine group were higher than those in the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S-100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo controls (0.1 microg/L) 20 hours after the start of rewarming (P =.01). The median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in the placebo group (P =.06).


CONCLUSIONS
The present data suggest that lamotrigine improves neurologic outcome after a prolonged period of hypothermic circulatory arrest.
Departments of Surgery and Anesthesiology and the Laboratory of Clinical Neurophysiology, Oulu University Hospital, Oulu, Finland.
V
V
Anttila
J
J
Rimpiläinen
M
M
Pokela
K
K
Kiviluoma
M
M
Mäkiranta
V
V
Jäntti
V
V
Vainionpää
J
J
Hirvonen
T
T
Juvonen
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D004569:Electroencephalography; D005260:Female; D006324:Heart Arrest, Induced; D006439:Hemodynamics; D007036:Hypothermia, Induced; D000077213:Lamotrigine; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents / Q000494:pharmacology*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D018709:Statistics, Nonparametric; D013552:Swine; D014227:Triazines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D014227:Triazines; D000077213:Lamotrigine