Novel rat cardiac arrest model of posthypoxic myoclonus.
We describe the time course of and pharmacology associated with auditory-induced muscle jerks following cardiac arrest in rats. The data indicate that several key features of this model mimic those of human posthypoxic myoclonus. Similar to the human form, the muscle jerks appear in the rats following an acute hypoxic episode (cardiac arrest). Initially, it is known that both spontaneous and auditory-induced myoclonus are present in these animals; some cardiac-arrested rats also exhibit seizures. Over the first few days after the arrest, episodes of both the seizure activity and spontaneous myoclonus disappear. The auditory-induced myoclonus continues to worsen, reaches a peak about 2 weeks after the arrest, then declines over time to subnormal levels. The auditory-induced muscle jerks exhibited by the cardiac arrested animals are attenuated by the typical antimyoclonic drugs 5-hydroxytryptophan, valproic acid, and clonazepam. In addition, the novel anticonvulsant felbamate was found to have antimyoclonic properties. The data suggest that this rat cardiac arrest model may be a valuable tool for investigating the pathophysiologic mechanisms of posthypoxic myoclonus and for developing new therapeutic strategies for treating the disorder.
Truong
D D
DD
Department of Neurology, California College of Medicine, University of California, Irvine 92717-4290.
Matsumoto
R R
RR
Schwartz
P H
PH
Hussong
M J
MJ
Wasterlain
C G
CG
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004831:Epilepsies, Myoclonic / Q000503:physiopathology*; D000078328:Felbamate; D006323:Heart Arrest / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009207:Myoclonus / Q000503:physiopathology*; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D002998:Clonazepam; D014635:Valproic Acid; D006916:5-Hydroxytryptophan; D000078328:Felbamate