EDEMA REDUCTION BY LEVEMOPAMIL IN FOCAL CEREBRAL-ISCHEMIA OF SPONTANEOUSLY HYPERTENSIVE RATS STUDIED BY MAGNETIC-RESONANCE-IMAGING

The effect of treatment with the Ca2+ channel blocker and 5-HT2 recept or antagonist levemopamil (recommended INN for (S)-emopamil) on the ex tent of ischaemic brain oedema was studied by magnetic resonance imagi ng in vivo. Focal cerebral ischaemia was induced in spontaneously hype rtensive rats by permanent middle cerebral artery occlusion. The treat ment consisted of slow intravenous injections of an aqueous solution o f levemopamil given immediately after middle cerebral artery occlusion and again 2 h and 4 h later. One group of animals (n = 17) received 3 X 2 mg/kg of levemopamil (total dose: 6 mg/kg) and another group (n = 13) received 3 x 4 mg/kg (total dose: 12 mg/kg). Saline was administe red to the controls (n = 16) at corresponding times. High-resolution T -2-weighted spin echo images were obtained 24 h after middle cerebral artery occlusion from two transversal brain planes (4.5 mm and 6.5 mm dorsal to the interaural line). Dose-dependent reductions of brain oed ema were achieved in both brain planes. The lower dose of levemopamil reduced the extent of oedema significantly (P < 0.05) by 20 +/- 3.7% i n the upper and by 21 +/- 3.8% in the lower brain plane as compared to the controls (means +/- S.E.M.). The higher dose diminished the exten t of oedema in the same planes by 30 +/- 3.5% and 31 +/- 4.0%, respect ively. Dose-dependent reductions of infarct size, as determined by vit al tissue staining using 2,3,5-triphenyltetrazolium chloride (TTC), we re observed in the levemopamil-treated groups. Body temperature was no t affected by levemopamil, suggesting direct cerebroprotection by this drug. The results of this magnetic resonance imaging study indicate t hat the extent of brain oedema and infarction is dose dependently redu ced by treatment with levemopamil in a clinically relevant stroke mode l.