[Protective effect of verapamil pretreatment against cerebral ischemia-reperfusion injury in gerbils].
OBJECTIVE
To observe the protective effect of verapamil pretreatment against cerebral ischemia-reperfusion injury in gerbils.


METHODS
Thirty-three Mongolian gerbils were randomized into the control group (group A, n=6, with sham operation), ischemia group (group B), and 3 verapamil groups (groups C, D, and E, n=7) with intraperitpneal verapamil injection (2 mg/kg) 48, 24 and 12 h before ischemia, respectively. In group A, the bilateral common carotid arteries were only exposed without clamping, and in the other 4 groups, the arteries were clamped for 20 min followed by reperfusion for 50 min. The gerbils were then decapitated and the forebrain cerebral cortex was removed to determine superoxide dismutase (SOD) and glutathione (GSH) activities and measure the contents of malondial dehyde (MDA), endothelin (ET) and calcitonin gene-related peptide (CGRP). The left forebrain cerebral cortex was sampled in each group to observe the ultrastructural changes under electron microscope.


RESULTS
In groups C and D, SOD activities were significantly higher than those in group B (P<0.05), and in group E, the SOD activity elevation was not statistically significant (P>0.05). In groups C, D and E, GSH activity was significantly higher than that in group B (P<0.05). MDA content was significantly lower in groups C and D than in group B (P<0.05), but comparable between groups E and B (P>0.05). ET content was also significantly lower in the pretreatment groups (P<0.05), but CGRP content higher (not statistically so, however) than those in group B. The more serious ultrastructural damage of the cerebral tissue was observed in group B, but only mild damage was found in the verapamil groups.


CONCLUSIONS
Verapamil given 12-48 h before cerebral ischemia may protect the gerbils from cerebral ischemia-reperfusion injury by enhancing SOD, GSH activities and decreasing ET content.
Department of Pathophysiology and Key Laboratory of Functional Proteomics of Guangdong Province, Southern Medical University, Guangzhou 510515, and Department of Anesthesiology, Affiliated Hospital of Guangzhou Medical College, China. xiaoning@fimmu.com
Ning
N
Ding
Fang
F
Wang
Hui
H
Xiao
Di-fen
DF
Wang
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016232:Endothelins / Q000378:metabolism; D005849:Gerbillinae; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D016232:Endothelins; D018015:Receptors, Calcitonin Gene-Related Peptide; D008315:Malondialdehyde; D014700:Verapamil; D013482:Superoxide Dismutase; D005978:Glutathione