Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging.
The effect of treatment with the Ca2+ channel blocker and 5-HT2 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 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 administered to the controls (n = 16) at corresponding times. High-resolution T2-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Elger
B
B
Research and Development, Knoll AG, Ludwigshafen, Germany.
Seega
J
J
Raschack
M
M
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014700:Verapamil / Q000031:analogs & derivatives* / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D014700:Verapamil; C052752:emopamil