The Reversibility of Cerebral Artery Contraction and Pathologic Change in the Rabbit Vasospasm Model

Kim, Ha Young; Han, Dae Hee; Chung, Chun Kee; Yang, Hee Jin; Kim, Hyun Jib; Kim, Yeon Mi; Chi, Je G; Cho, Byung Kyu

Abstract

Although it is well known that cerebral vasospasm is caused by the breakdown of blood products extravasated during subarachnoid hemorrhage(SAH), it is still controversial whether its persistence is caused by the continuing contraction of the smooth muscle of vessels or by morphologic change in the vessel wall. The purpose of this study is to evaluate the reversibility of vasospasm induced by intra-arterial papaverine injection and to evaluate morphological change in the vessel wall in SAH induced in rabbits. In each of 18 rabbits, vertebral angiography was performed 7 days before the induction of artificial SAH was made by injection of autologous arterial blood around the basilar artery through a silicone catheter placed in the prepontine cistern. Before and after the injection of papaverine, further vertebral angiograms were obtained on days 1(n=1), 2(n=2), 3(n=1), 4(n=2), 5(n=4), 6(n=1), 7(n=2), 8(n=1), 14(n=1), 16(n=1) and 30(n=1) after the creation of SAH. Immediately after this further angiography, the rabbits were sacrificed and portions of the basilar artery were prepared for electron microscopic(EM) study and immunohistochemical staining. Vasospasm of the basilar artery was most severe in the rabbit sacrificed one day after SAH(54.1% of pre-SAH diameter) and maintained until 30 days thereafter(61.0% of the pre-SAH diameter). Five days after SAH, the diameter of the basilar artery following papaverine injection was 78.6% of its pre-SAH diameter, suggesting a decrease in the reversibility of papaverine-induced effects. The ultrastructural changes seen on EM study were most remarkable on post-SAH days 1 and 2 and tended to be gradually milder on later days. Immunohistochemical staining showed diffuse strong positive reactivity for smooth muscle actin in the media at 1, 5, 7, and 14 days after SAH, and strong positive reactivity for vimentin in the intima and media at 2, 5, and 30 days after SAH. When the reversibility of papaverine-induced arterial contraction decreased, findings of increased immunoreactivity to the cytoskeletal protein of smooth muscle of the basilar artery suggested that morphological changes in the artery wall had contributed to the maintenance of vasospasm.