Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs

Objective: The potent antioxidant LY231617 (2,6-bis(1,1-dimethylethyl)-4-[[ (1-ethyl)amino]methyl]phenol hydrochloride) is cytoprotective in models of focal and global cerebral ischemia. We tested the hypothesis that administr ation of LY231617, before the insult, would improve recovery of cerebral el ectrical activity and metabolic function after transient global cerebral is chemia by improving cerebral blood flow (CBF) during the reperfusion period , Design: Randomized, controlled, prospective study. Setting: Research laboratory at a university teaching hospital. Subjects: Twenty-four male beagle dogs. Interventions: All experiments were performed under pentobarbital anesthesi a and controlled conditions of normoxia, normocarbia, and normothermia, Twe lve control dogs received 20 mL/kg saline (vehicle) bolus into the right at rium and 0.01 mL/kg/min iv, beginning 20 mins before 13 mins of global cere bral ischemia (by aortic occlusion), The dogs in the drug-treated group rec eived LY231617 as a 10-mg/kg bolus 20 mins before ischemia and 5 mg/kg/hr t hroughout reperfusion (n = 12), CBF was measured using radiolabeled microsp heres. Measurements and Main Results: Total CBF, cerebral oxygen consumption, and somatosensory evoked potentials (SEP) were measured during 240 mins of repe rfusion, CBF was similar in both vehicle- and LY231617-treated animals at b aseline and throughout the experimental period. In ail animals, SEP became isoelectric between 60 and 100 sees after cross-clamping of the ascending a orta. SEP amplitude recovery was significantly higher in drug-treated anima ls compared with controls (73% +/- 15% vs. 39% +/- 14% [mean +/- SEM] from baseline at 120 mins [p < .05] and 86% +/- 12% vs. 49% +/- 14% from baselin e at 240 mins [p < .05]), Conclusions: LY231617 improves recovery of cerebral electrical function aft er complete transient global ischemia via mechanisms unrelated to cerebral circulatory effects.