Delayed therapy of experimental global cerebral ischemia with acetyl-L-carnitine in dogs.
Acetyl-L-carnitine (ALCAR), when administered immediately following restoration of spontaneous circulation (ROSC) from experimental cardiac arrest (CA) has previously been demonstrated to promote normalization of brain energy metabolism and neurologic recovery following 10 min CA. In order to determine ultimate efficacy for this or other drugs, clinical trials must be performed in human subjects. In several human clinical trials, though, drug administration has been significantly delayed following resuscitation from CA. These experiments test the hypothesis that post-resuscitative delay in ALCAR administration will impair the ability of this drug to promote neurologic recovery. Neurological deficit scoring (23 h) as well as frontal cortex lactate levels (2 and 24 h) were compared following resuscitation from 10 min CA in dogs receiving either ALCAR or drug vehicle 30 min following ROSC. Dogs treated with ALCAR 30 min following ROSC from 10 min CA exhibited more normal cerebral cortex lactate levels than did vehicle control animals. There was no difference, however, in neurologic deficit scores between groups, with all animals demonstrating moderate to severe clinical neurologic impairment at 23 h following ROSC. A 30-min delay in ALCAR administration following ROSC from 10 min CA impairs the ability of this drug to promote neurologic recovery despite apparent normalization of brain lactate levels.
Rosenthal
Robert E
RE
Program in Trauma, Department of Surgery, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201, USA. rrosenthal@umm.edu
Bogaert
Yolanda E
YE
Fiskum
Gary
G
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004285:Dogs; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy; D009460:Neurologic Examination / Q000379:methods; D018697:Nootropic Agents / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018697:Nootropic Agents; D000108:Acetylcarnitine