B. Elger et al., EDEMA REDUCTION BY LEVEMOPAMIL IN FOCAL CEREBRAL-ISCHEMIA OF SPONTANEOUSLY HYPERTENSIVE RATS STUDIED BY MAGNETIC-RESONANCE-IMAGING, European journal of pharmacology, 254(1-2), 1994, pp. 65-71
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.