Long-term neurological assessment of the post-resuscitative effects of flunarizine, verapamil and nimodipine in a new model of global complete ischaemia.
In anesthetized rats, global complete ischaemia lasting for 9 min was induced by controlled hydraulic compression of the chest. A neurological score, based on cranial and spinal reflexes, postural tone, gait, movement and limb placement, was determined at 2 hr and 1, 2, 3, 7, 14, 21 and 28 days after resuscitation. Three doses of three calcium antagonists, flunarizine, verapamil and nimodipine and their respective solvents, were given intravenously during the resuscitation. The total neurological score was significantly better than solvent with 0.16 and 0.63 mg/kg of flunarizine and 0.04 and 0.16 mg/kg of verapamil; it was significantly better with solvent (10% ethanol) than with 0.04 and 0.16 mg/kg of nimodipine. The deficiency in tactile placing reactions of the hindpaws was the most resistant to therapy. This non-invasive model of global ischaemia in rats seems useful for the evaluation of drugs, since it requires minimal anesthesia and allows assessment of neurological recovery over an extended period of time.
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
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Wauquier
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Melis
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Janssen
D000758:Anesthesia; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D005444:Flunarizine / Q000494:pharmacology*; D007275:Injections, Intravenous; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D012018:Reflex / Q000187:drug effects; D012151:Resuscitation; D014700:Verapamil / Q000494:pharmacology*
D009553:Nimodipine; D014700:Verapamil; D005444:Flunarizine