Experimental chronic cerebrovascular spasm in the monkey: an assessment of the functional changes in the cerebral arteries and their protection by diltiazem.
The structure and function of cerebral arteries obtained from a monkey model of chronic cerebral vascular spasm 5 days after hemorrhage have been examined. Narrowing of the larger cerebral arteries demonstrated by angiography at all sites of measurement seems to be due primarily to an increased wall rigidity associated with cellular damage, the resultant inflammatory response and large, long-lasting spontaneous increases in muscle tone. Changes in agonist sensitivity were extremely variable. The reduction of contractility of the vessel wall to a mean of 30% of control diminished the consequence of any changes in active tone characteristics. Neurogenic control on the side of the lesion was remarkably depressed. When treated with diltiazem, beginning 1 day before induction of hemorrhage and continuing to the time of sacrifice, arterial diameter was reduced at only 1 of the 6 standard sites of measurement and then by only a small amount. Neurologic effects invariably seen in the untreated monkeys were prevented by diltiazem. Many of the changes in the artery wall, including structural alterations, were diminished by the drug. Abnormal spontaneous myogenic tone was present but was less in the diltiazem-treated group; however, nerve damage and its functional consequences were not prevented. It is concluded that diltiazem, presumably by preventing the accumulation of intracellular calcium within the cell, prevents the initial events in the evolution of chronic cerebrovasospasm or narrowing. This is probably achieved by a diminishing of the direct vasoconstrictor effects and the toxicity of putative spasmogens released from blood clots, nerves and the brain on the vascular smooth muscle, thus interrupting the sequence leading to pathologic change.
J A
JA
Bevan
R D
RD
Bevan
J G
JG
Frazee
D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology; D004110:Diltiazem / Q000627:therapeutic use*; D007473:Ion Channels / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008254:Macaca nemestrina; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects
D001552:Benzazepines; D007473:Ion Channels; D004110:Diltiazem