Lack of a neuroprotective effect from N-acetylcysteine after cardiac arrest and resuscitation in a canine model.

Abstract

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. 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). 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). 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.