Effect of gamma knife irradiation on relaxation and contraction responses of the common carotid artery in the rat.

Abstract

This report concerns a pilot study of the short- and long-term effects of gamma knife radiosurgery on vascular responses. The investigation was carried out on male Sprague-Dawley rats, and the relaxation and contraction responses of the right common carotid artery (CCA) were assessed following irradiation (100 Gy). The non-treated CCA of the same animals served as internal controls. Non-irradiated rats were used to control the effect of normal aging on vascular function. Isometric tension was determined on in vitro preparations of arterial rings. Acetylcholine-mediated, endothelium-dependent relaxation was impaired one month after radiosurgery, as was endothelium-independent relaxation induced by sodium nitroprusside, but the effect on the latter was minimal. The irradiated CCA was also impaired with respect to contraction responses induced by norepinephrine, endothelin-1 or phorbol dibutyrate. This impairment appeared to be biphasic, as it was evident one day after radiosurgery, followed by a partial recovery one week later, and again manifest after one month. At the light microscope level, the carotid arteries appeared to be well preserved throughout the experiment. However, obvious ultrastructural changes were noted in endothelial and smooth muscle cells of specimens obtained three months after radiosurgery. The present data indicate that high dose gamma knife radiosurgery affects the functions of both, the vascular endothelium and the vascular smooth muscles in an apparent time-dependent fashion. Because of its increasing application to patients, there is the need for studying the effects of gamma knife radiosurgery on cerebral arteries, since functional vascular changes may occur in the absence of obvious histological alterations. Our results on CCAs point to the feasibility of such experimental investigations.