A new ergopeptide, CBM 36-733, improves ischaemic cerebral metabolism in spontaneously hypertensive rats.
The authors have examined the protective effects of CBM 36-733 (2-methyl-alpha-ergocryptine) on experimental cerebral ischaemia in spontaneously hypertensive rats (SHR). SHR aged 6 months were divided into four groups; a vehicle-treated group, and CBM 36-733 0.01, 0.1 or 1.0 mg/kg i.v. treated groups. After anaesthesia, the bilateral common carotid artery was ligated (BCL) and supratentorial cerebral ischaemia was produced for 1 h. Cerebral blood flow to the parietal cortex was repeatedly measured by the H2 clearance technique. Brain tissue lactate, adenosine triphosphate (ATP) and pyruvate were determined by enzymatic methods. By BCL, cerebral cortical blood flow decreased to 9-19% of the resting value at 30 min and further to 5-11% at 60 min. Blood flow reduction was not altered by CBM 36-733 administration. At 1 h ischaemia, brain tissue lactate greatly increased to 27.5 +/- 2.6 (mean +/- SEM) mmol/kg in the vehicle-treated SHR, while it showed less increase, to 7.5 +/- 1.4, in the CBM 36-733 0.1 mg/kg group. Brain ATP decreased to 1.31 +/- 0.05 in vehicle-treated SHR after 1 h BCL, but it changed little, retaining almost normal levels (2.60 +/- 0.19) in rats treated with 0.1 mg/kg CBM 36-733, followed by 1.0 and 0.01 mg/kg, suggesting a beneficial effect of CBM 36-733 on the ischaemic cerebral metabolism. The present results suggest that CBM 36-733 has a protective effect on the brain against ischaemia by improving cerebral metabolism while not affecting haemodynamics.
Sadoshima
S
S
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka City, Japan.
Ibayashi
S
S
Nakane
H
H
Okada
Y
Y
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004873:Ergolines / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011918:Rats, Inbred SHR
D004873:Ergolines; D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; C067380:mergocriptine; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate