Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging

Abstract

The effect of treatment with the Ca 2+ channel blocker and 5-HT 2 receptor antagonist levemopamil (recommended INN for ( S)-emopamil) on the extent of ischaemic brain oedema was studied by magnetic resonance imaging in vivo. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent middle cerebral artery occlusion. The treatment consisted of slow intravenous injections of an aqueous solution of levemopamil given immediately after middle cerebral artery occlusion and again 2 h and 4 h later. One group of animals ( n = 17) received 3 × 2 mg/kg of levemopamil (total dose: 6 mg/kg) and another group ( n = 13) received 3 × 4 mg/kg (total dose: 12 mg/kg). Saline was administered 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 oedema were achieved in both brain planes. The lower dose of levemopamil reduced the extent of oedema significantly ( P < 0.05) by 20 ± 3.7% in 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 extent of oedema in the same planes by 30 ± 3.5% and 31 ± 4.0%, respectively. Dose-dependent reductions of infarct size, as determined by vital tissue staining using 2,3,5-triphenyltetrazolium chloride (TTC), were observed in the levemopamil-treated groups. Body temperature was not affected by levemopamil, suggesting direct cerebroprotection by this drug. The results of this magnetic resonance imaging study indicate that the extent of brain oedema and infarction is dose dependently reduced by treatment with levemopamil in a clinically relevant stroke model.