NOVEL RAT CARDIAC-ARREST MODEL OF POSTHYPOXIC MYOCLONUS

We describe the time course of and pharmacology associated with audito ry-induced muscle jerks following cardiac arrest in rats. The data ind icate that several key features of this model mimic those of human pos thypoxic myoclonus. Similar to the human form, the muscle jerks appear in the rats following an acute hypoxic episode (cardiac arrest). Init ially, it is known that both spontaneous and auditory-induced myoclonu s are present in these animals; some cardiac-arrested rats also exhibi t seizures. Over the first few days after the arrest, episodes of both the seizure activity and spontaneous myoclonus disappear. The auditor y-induced myoclonus continues to worsen, reaches a peak about 2 weeks after the arrest, then declines over time to subnormal levels. The aud itory-induced muscle jerks exhibited by the cardiac arrested animals a re attenuated by the typical antimyoclonic drugs 5-hydroxytryptophan, valproic acid, and clonazepam. In addition, the novel anticonvulsant f elbamate was found to have antimyoclonic properties. The data suggest that this rat cardiac arrest model may be a valuable tool for investig ating the pathophysiologic mechanisms of posthypoxic myoclonus and for developing new therapeutic strategies for treating the disorder.