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 administration of LY231617, before the insult, would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow (CBF) during the reperfusion period.


METHODS
Randomized, controlled, prospective study.


METHODS
Research laboratory at a university teaching hospital.


METHODS
Twenty-four male beagle dogs.


METHODS
All experiments were performed under pentobarbital anesthesia and controlled conditions of normoxia, normocarbia, and normothermia. Twelve control dogs received 20 mL/kg saline (vehicle) bolus into the right atrium and 0.01 mL/kg/min i.v., beginning 20 mins before 13 mins of global cerebral ischemia (by aortic occlusion). The dogs in the drug-treated group received LY231617 as a 10-mg/kg bolus 20 mins before ischemia and 5 mg/kg/hr throughout reperfusion (n = 12). CBF was measured using radiolabeled microspheres.


RESULTS
Total CBF, cerebral oxygen consumption, and somatosensory evoked potentials (SEP) were measured during 240 mins of reperfusion. CBF was similar in both vehicle- and LY231617-treated animals at baseline and throughout the experimental period. In all animals, SEP became isoelectric between 60 and 100 secs after cross-clamping of the ascending aorta. SEP amplitude recovery was significantly higher in drug-treated animals compared with controls (73%+/-15% vs. 39%+/-14% [mean+/-SEM] from baseline at 120 mins [p<.05] and 86%+/-12% vs. 49%+/-14% from baseline at 240 mins [p< .05]).


CONCLUSIONS
LY231617 improves recovery of cerebral electrical function after complete transient global ischemia via mechanisms unrelated to cerebral circulatory effects.
Toung
T J
TJ
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bhardwaj
A
A
Wang
M
M
Kirsch
J R
JR
Traystman
R J
RJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D001786:Blood Glucose; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory; D019344:Lactic Acid / Q000097:blood; D008297:Male; D010101:Oxygen Consumption; D011446:Prospective Studies; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects
D000975:Antioxidants; D001786:Blood Glucose; D002084:Butylated Hydroxytoluene; D019344:Lactic Acid; C081064:LY 231617