Clentiazem protects against chronic cerebral vasospasm in rabbit basilar artery.
OBJECTIVE
Experiments were carried out in rabbits to determine whether clentiazem (8-chlorodiltiazem), a cerebrovascular-selective calcium channel blocker, administered 24 hours before subarachnoid hemorrhage influenced the subsequent cerebral vasospasm.


METHODS
Subarachnoid hemorrhage was induced by multiple injections of blood into the prepontine cisterns of 35 male New Zealand White rabbits, and clentiazem (5 mg/kg) was administered 4 times daily until sacrifice. Cerebral artery diameter was assessed in vivo by angiography. Functional features of basilar arteries were measured using conventional in vitro methodology.


RESULTS
Clentiazem reduced the angiographic narrowing seen on days 2 and 5 from 35% and 34%, respectively (sham control, 1.42 +/- 0.31 mm [n = 22]), to 8% and 11%, respectively, and prevented the narrowing (32%) that occurred on day 9. Narrowing in the untreated rabbits was only partly reversed by papaverine; all narrowing in clentiazem-treated animals was papaverine sensitive. Clentiazem prevented or reduced many of the changes in the basilar artery caused by the subarachnoid hemorrhage. Of particular relevance to arterial narrowing were the increased wall stiffness, the transient spontaneous changes in wall force, and the reduction in relaxation to acetylcholine. Reduction of the changes in wall force induced by agonists and by stimulation of intramural sympathetic nerves was observed.


CONCLUSIONS
The vascular damage associated with chronic cerebral vasospasm is related to calcium entry into the smooth muscle and endothelial cells, and possibly sympathetic nerve terminals, through calcium channels sensitive to clentiazem, which suggests that clentiazem may be of value in the management of chronic cerebral vasospasm.
Vorkapic
P
P
Department of Pharmacology, College of Medicine, University of Vermont, Burlington 05405.
Bevan
J A
JA
Bevan
R D
RD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002533:Cerebral Angiography; D002908:Chronic Disease; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D008297:Male; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000502:physiology
D002121:Calcium Channel Blockers; C056595:clentiazem; D004110:Diltiazem; D000109:Acetylcholine