Functional arterial changes in chronic cerebrovasospasm in monkeys: an in vitro assessment of the contribution to arterial narrowing.

Abstract

Cerebral arteries from monkeys with chronic cerebral vasospasm arising from experimental subarachnoid hemorrhage produced 5-6 days previously were examined for changes in their functional properties in an attempt to understand the basis of the narrowing. Hemorrhage was caused by puncture of the internal carotid artery just proximal to the cirde of Willis. Segments taken close to the origins of the anterior and middle cerebral arteries consistently showed decreased extensibility. In addition, they exhibited large, prolonged, spontaneous increases in muscle tone. Other alterations observed include a marked reduction in the capacity of the vessel wall to contract, reduction in constrictor and dilator nerve influences on vascular tone, and some increased sensitivity to serotonin. Small pial arteries (150-200 urn o.d.) from the side of the injury showed large spontaneous irregular increases in tone. It is proposed that 5-6 days after experimental subarachnoid hemorrhage in monkeys the change most responsible for persistent narrowing in the larger arteries is an increased rigidity of the vessel wall. This is probably caused by an inflammatory response. In the smaller arteries, abnormal spontaneous contractile activity is a major factor in narrowing. This activity is not stretch-dependent. We suggest that the Initial cause of the arterial narrowing after hemorrhage is the action of vasoactive substances released in the close vicinity of the arterial wall, which lead to tissue damage, abnormal tone, and an inflammatory response with flbrosis. (Stroke 1987;18:472-481)

Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage.

“…6 In another model, we found that a decrease in vessel wall distensibility and a loss of contractility were the dominant features of segments taken from narrowed arteries 6 days after SAH in monkeys; the greatest narrowing occurred in those vessels that had the least capacity to contract. 18 The measurements we made in this experiment in rabbits are similar to those we made previously in monkeys.…”

“…In rabbits, both these indexes increased following SAH after a latency of several days and both could be correlated with pathophysiologically significant papaverine-insensitive narrowing seen on angiography. The extent of vessel wall damage, expressed as the loss of contractility (the most important role of the cerebral arteries) was 30% in a monkey model on day 6 18 and approximately 50% in our rabbit model from days 6 to 9. In this regard the maximum responses of the cerebral arteries to 5-HT, NE, and K + were decreased 7 days after large-volume SAH in monkeys 27 and dogs.…”

Induction of housekeeping gene expression after subarachnoid hemorrhage in dogs

“…There are, however, some differences between vasospasm and these diseases. While reduced arterial compliance is well documented during vasospasm, presence of the other features has not been rigorously shown (Bevan et al, 1987;Macdonald et al, 1995).…”

“…Vasospastic arteries have reduced compliance and this has been suggested to indicate that there has been vascular remodeling (Bevan et al, 1987;Macdonald et al, 1995). Vascular remodeling is an active process by which blood vessels respond to alterations in hemodynamics and involves cell growth, death and migration and production and degradation of the extracellular matrix (Gibbons and Dzau, 1994).…”

“…Vasospasm has been difficult to prevent or reverse with vasodilators, however, leading to the suggestion that structural changes occur in the cerebral arteries and that these contribute to the narrowing (Bevan et al, 1987;Ohkuma et al, 2001; Correspondence and Reprint Requests: R. Loch Macdonald, M.D., Ph.D., Division of Neurosurgery, St. Michael's Hospital, 30 Bond Street,Toronto,Ontario,M5B 1W8,Canada,Phone: (416) 864 5452,Fax: (416) 864 5634, Email: Macdonaldlo@smh.toronto.on.ca. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”