Effects of aging on cerebral vasospasm after subarachnoid hemorrhage in rabbits

The effects of aging on cerebral vasospasm after subarachnoid hemorrhage (SAH) remain to be elucidated. The aim of this study was to clarify age-related differences of vasospasm and of papaverine reactivity in the responses of basilar arteries after SAH in rabbits.

Rabbits receiving a single injection of arterial blood into the cisterna magna were divided into 3 groups: young (2 to 3 months old), adult (6 to 9 months old), and old (20 to 40 months old). Vertebrobasilar angiograms were obtained before SAH and 1, 2, 4, and 7 days after SAH. Papaverine was administrated selectively via the vertebral artery on day 2, and serial angiography was performed for up to 2 hours. Vessel structures were assessed with light microscopy on days 1, 2, 4, and 7 after SAH and at 10, 30, and 60 minutes after papaverine infusion.

Mortality from SAH in old rabbits was 40%, whereas that of young and adult rabbits was 0%. Angiograms revealed that SAH induced maximal constriction of the basilar arteries on day 2 in all age groups, and the constrictions were significantly increased with age at all time points investigated. The degree of dilatation of spastic basilar arteries after intra-arterial papaverine administration significantly decreased with age. Duration of the efficacy of papaverine became significantly shorter with age. Vessel diameter returned to the preinfusion value approximately 120, 60, and 30 minutes after infusion in young, adult, and old rabbits, respectively. Light microscopy in old rabbits showed luminal narrowing and corrugation of the internal elastic lamina not only in the basilar arteries but also in small arteries and intraparenchymal arterioles.

This study suggests that aging increases the degree of vasospasm in rabbits. The impaired reactivity to papaverine with aging might imply the early transition of the aged vessel to the papaverine-resistant chronic stage.