Effect of the calcium entry blocker nimodipine on the metabolism of nucleic acids in rat brain ischemia.
The effect of nimodipine, a 1,4 dihydro-piridine calcium entry blocker (200 micrograms/kg), was investigated in rats after definitive ischemia or 2 min of global ischemia (neck tourniquet method). The brains were freeze-clamped at the desired time intervals and subjected to high pressure liquid chromatography analyses for nucleotides and enzymatic lactate estimation. Although in the definitive ischemia (removal of the brain) no difference was observed in the treated versus the untreated animals, there was a statistically significant difference in both groups after global ischemia followed by reperfusion. Thirty minutes after reflow the brains of the treated animals contained 1,690 +/- 62 nmol ATP/g as compared to 765 +/- 259 nmol ATP/g in the untreated animals (p less than 0.05). The normal controls amounted to 1,932 +/- 77 nmol ATP/g. Also the adenylate energy charge returned to normal in the treated animals (treated animals and controls 0.69 and 0.72, respectively). From these preliminary data we conclude that nimodipine is able to restore mitochondrial function after ischemia and to maintain a high level of energy-rich phosphates. Thus, calcium entry blockers may be effective in preserving and protecting cerebral tissue from irreversible injury after ischemia.
Clinic for Neurosurgery, University of Innsbruck, Austria.
H
H
Kostron
W
W
Sperl
C
C
Murr
K
K
Pillwein
D000227:Adenine Nucleotides / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D015424:Reperfusion
D000227:Adenine Nucleotides; D007773:Lactates; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D009553:Nimodipine