Nimodipine improves brain energy metabolism and blood rheology during ischemia and reperfusion in the gerbil brain.
Whether nimodipine improves cerebral blood flow (CBF) and metabolism in cerebral ischemia remains a controversial issue. We investigated the effect of nimodipine on CBF, brain energy metabolism, using a laser-Doppler flowmeter and in vivo 31phosphorus nuclear magnetic resonance (31P NMR) spectroscopy, and blood rheology during forebrain ischemia and reperfusion in gerbils. Eighty-three adult gerbils received nimodipine (1 micrograms/kg/min), or an equal volume of the vehicle, or saline, over 60 min prior to a transient forebrain ischemia for 60 min. We measured sequential changes in phosphocreatine (PCr) / inorganic phosphate (Pi) ratio, beta-ATP/Pi ratio, and intracellular pH (pHi) during ischemia and reperfusion by 31P NMR spectroscopy, and the measurement of whole blood viscosity (WBV) at 60 min after reperfusion. CBF was measured continuously throughout the study by a laser-Doppler flowmeter. During forebrain ischemia, PCr/Pi and beta-ATP/Pi ratios were higher significantly in the nimodipine-treated group (p < 0.05 and 0.01) than in the vehicle- or saline-treated groups. During reperfusion, PCr/Pi and beta-ATP/Pi ratios recovered significantly only in the nimodipine-treated group (p < 0.05 and 0.01). The WBV at high shear rate (562.5 s-1) lowered significantly in the nimodipine-treated group (p < 0.05) compared with the vehicle- or saline-treated group. CBF was higher significantly only during administration of nimodipine in the nimodipine-treated group (p < 0.01) than other groups. Nimodipine improved brain energy metabolism and blood rheology during forebrain ischemia and reperfusion in the gerbil brain.
Ichihara
S
S
Second Department of Internal Medicine, Kagawa Medical School, Japan.
Tsuda
Y
Y
Hosomi
N
N
Kitadai
M
M
Matsuo
H
H
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects*; D005849:Gerbillinae; D017078:Laser-Doppler Flowmetry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D010758:Phosphorus; D016548:Prosencephalon / Q000098:blood supply; D015427:Reperfusion Injury / Q000517:prevention & control; D012212:Rheology
D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D010758:Phosphorus; D009553:Nimodipine