Lack of a neuroprotective effect from N-acetylcysteine after cardiac arrest and resuscitation in a canine model.
OBJECTIVE
Oxygen free radicals cause brain injury following resuscitation from cardiac arrest. In preclinical trials, some free radical scavenging drugs reduce oxidative neuronal damage after ischemia and reperfusion, but these drugs are generally not yet available for clinical testing or use. N-Acetylcysteine (NAC), a commonly used antidote in acetaminophen poisoning, is also a potent free radical scavenger that can ameliorate oxidative injury following ischemia and reperfusion in neuronal cell culture. We hypothesized that treatment with NAC would improve neurological outcome after cardiac arrest and resuscitation.


METHODS
In 16 adult female beagles, 10 min of ventricular fibrillation was followed by 3 min of open-chest CPR, and defibrillation. Immediately following return of spontaneous circulation, animals randomly received either 150 mg/kg NAC (3% solution) (n = 8) or an equivalent volume of normal saline (n = 8). Twenty-three hours later, neurological deficit was scored (0 = normal, 100 = brain death).


RESULTS
All animals were successfully resuscitated, and there were no apparent adverse effects to the administration of NAC in post resuscitative animals. There was, however, no significant difference in neurological deficit in the animals receiving NAC (40 +/- 12.9, mean +/- SD) compared to control animals (44 +/- 6.5, P = 0.73).


CONCLUSIONS
No neuroprotective effect was found from the administration of NAC at currently used clinical dosages, to dogs subjected to 10 min of global cerebral ischemia from cardiac arrest and resuscitation.
Silbergleit
R
R
Section of Emergency Medicine, University of Michigan, Ann Arbor 48109, USA. robie@umich.edu
Haywood
Y
Y
Fiskum
G
G
Rosenthal
R E
RE
D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006323:Heart Arrest / Q000188:drug therapy* / Q000628:therapy; D012016:Reference Values; D013997:Time Factors; D014693:Ventricular Fibrillation
D016166:Free Radical Scavengers; D000111:Acetylcysteine