Okada T, Harada T, Bark D H, Mayberg M R
Department of Neurological Surgery, University of Washington, Seattle.
Neurosurgery. 1990 Sep;27(3):349-56. doi: 10.1097/00006123-199009000-00002.
A new animal model for vasospasm using rat femoral artery has been developed. Whole blood, washed erythrocytes, or leukocytes in platelet-rich plasma were selectively applied to the adventitial surface of the femoral artery for 7 days in 15 rats, after which the vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. As compared with matched control arteries, there was a prominent reduction in luminal cross-sectional area after 7 days in vessels exposed to whole blood or washed erythrocytes, but not in those exposed to leukocytes in platelet-rich plasma. In arteries with luminal narrowing, light and transmission electron microscopy demonstrated marked morphological changes throughout the vessel wall similar to those seen in cerebral vasospasm after subarachnoid hemorrhage. Immunohistochemistry disclosed a prominent loss of immunoreactive actin in smooth muscle cells of arteries exposed to whole blood or erythrocytes. To assess the time course of arterial narrowing in this model, whole blood was selectively applied to the adventitial surface of femoral arteries in 23 rats for periods from 2 to 20 days. As compared with control arteries, arterial narrowing was variably present at 2 days, progressively increased by 5 days, was maximal at 7 to 10 days, and returned to near control levels by 20 days. The presence and severity of ultrastructural changes in vessel wall corresponded to the degree of arterial narrowing over time. These results suggest that chronic narrowing in rat femoral artery exposed to periadventitial blood is analogous to that observed in cerebral arterial vasospasm after subarachnoid hemorrhage. This new model represents a simple and reliable means to investigate pathogenic mechanisms and potential therapies for vasospasm.
一种使用大鼠股动脉的血管痉挛新动物模型已被开发出来。在15只大鼠中,将全血、洗涤过的红细胞或富含血小板血浆中的白细胞选择性地应用于股动脉外膜表面7天,之后对血管进行灌注固定,并通过光镜、透射电镜和免疫组织化学进行检查。与配对的对照动脉相比,暴露于全血或洗涤过的红细胞的血管在7天后管腔横截面积显著减小,但暴露于富含血小板血浆中白细胞的血管则没有。在管腔狭窄的动脉中,光镜和透射电镜显示整个血管壁有明显的形态学变化,类似于蛛网膜下腔出血后脑血管痉挛所见。免疫组织化学显示,暴露于全血或红细胞的动脉平滑肌细胞中免疫反应性肌动蛋白显著丢失。为了评估该模型中动脉狭窄的时间进程,在23只大鼠中,将全血选择性地应用于股动脉外膜表面2至20天。与对照动脉相比,动脉狭窄在2天时可变地出现,在5天时逐渐增加,在7至10天时最大,到20天时恢复到接近对照水平。血管壁超微结构变化的存在和严重程度随时间与动脉狭窄程度相对应。这些结果表明,暴露于外膜周围血液的大鼠股动脉慢性狭窄类似于蛛网膜下腔出血后观察到的脑动脉痉挛。这种新模型是研究血管痉挛发病机制和潜在治疗方法的一种简单而可靠的手段。