Effects of nimodipine on infarct size and cerebral acidosis after middle cerebral artery occlusion in the rat.
The objective of this study was to determine the effect of nimodipine on infarct development and local brain pH after middle cerebral artery occlusion in the rat. Female Fischer-344 rats were subjected to permanent occlusion of the left middle cerebral artery by electrocoagulation. After 6, 12, or 24 hours, brains were frozen, and infarct size, degree of edema formation, and local brain pH were quantified by standard histology or the umbelliferone technique, respectively. In control rats, cortical infarct size was increased from 29.5 microliters at 6 hours to 72.5 microliters at 24 hours after vessel occlusion. In striatum only, an insignificant increase from 15.2 to 24.7 microliters in infarct volume was observed during this period. Edema increased from 7% to 22% in cortical and from 4% to 39% in the striatal infarct areas during this time. Nimodipine (0.1 mg/kg s.c.), given 45 minutes before and again 8 and 16 hours after middle cerebral artery occlusion, did not alter infarct size at 6 hours but considerably improved outcome at later times. Edema formation was lower at 12 hours in the group treated with the calcium antagonist (p less than 0.05). By contrast, effects on local brain pH were seen as early as 6 hours after the vessel occlusion. Nimodipine greatly reduced the areas exhibiting the lowest pH values beyond pH 6.0 (p less than 0.05). Similar effects by nimodipine on brain pH were observed in the 12-hour series, whereas at 24 hours after middle cerebral artery occlusion, a shift to more alkalotic values was noted with no overt differences between control and drug-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Bielenberg
G W
GW
Institut für Pharmakologie und Toxikologie, Marburg, FRG.
Burniol
M
M
Rösen
R
R
Klaus
W
W
D000138:Acidosis / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000517:prevention & control; D002536:Cerebral Arteries / Q000601:surgery; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004564:Electrocoagulation; D005260:Female; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051381:Rats; D011916:Rats, Inbred F344