STEROLOGY AND RHEOLOGY OF INTIMA DAMAGE AT BIFURICATIONS

对于特定的血流动力学应力，需要检验的假设是：(I) 大脑动脉分叉处的损害比邻近的更严重 或在颅外分叉处，以及(Ii)这种损害是由 从内膜上看。 大脑动脉分叉的结构将在 主动脉缩窄高血压、动脉粥样硬化或颈动脉狭窄的兔 结扎和人类尸检。重点将放在年轻成年男性身上 有适当控制的兔子。定量的体视学方法将 被用来评论血管内皮细胞、平滑肌的作用 (SM)和内弹性板(IEL)可能存在的机械薄弱 导致动脉粥样硬化和动脉瘤形成的动脉壁。 与动脉分叉结构相关的具体目标和 内侧间隙是(A)确定的图案和准确的方向 内皮细胞和SM细胞(B)绘制出分布、位置和大小 在IEL(C)中的窗口的任何比例的差异量化 分叉壁的组成与非分叉节段的比较(D) 确定细胞和细胞之间的排列和相互关系 血管内膜的脱细胞成分。这些结构参数将是 比较取决于(I)位置(Ii)压力或流量和(Iii) 是否存在相关病理(动脉粥样硬化或动脉瘤)。 人类的大脑循环有很高的中间缺陷的发生率， 微小动脉瘤和囊状动脉瘤，可能破裂导致 蛛网膜下腔出血和动脉痉挛。人们认为，一种组合 先天和/或后天因素可能导致动脉瘤的形成 和破裂，但到目前为止还没有公认的病因。施泰本斯(1)说 “关于退行性改变和血流动力学的进一步信息 动脉分叉处的压力是制定更详细大纲的前提 脑动脉瘤的发病机制“。只有数量上的 结合力学分析的体视学方法可以提供这一点 信息。实验研究的修订工作将会加强，因为 兔和人脑血管的形态非常相似。 考虑到蛛网膜下腔的发病率、死亡率和发病率 对于出血，重要的是要回答有关初始 分叉结构的变化可能是 可能导致风险重新评估的脑动脉瘤的发病机制 各种因素。 超过一半的美国人死于心血管疾病，其中大多数 与动脉粥样硬化过程有关，这个过程主要是 由于家族性高胆固醇血症，不到5%的病例(2)。 喂饲胆固醇的兔子将提供脂肪沉积的数据 颈动脉、大脑和耳朵分叉。但是改变了血压和 心流可以提供对多因素和协同的洞察 导致内膜垫在侧角形成的改变和 关于分叉的其他站点。导致异常的相同因素 小脑血管通透性可能是血管内膜改变的一个因素 更大的分叉。 此外，由于钙离子进入阻滞剂可能具有保护作用 针对内皮和SM损伤，这些药物的临床剂量将是 用于评估它们是否有助于预防观察到的损伤或增强其 回归。

For specific hemodynamic stresses, the hypotheses to be tested are that (i) damage is more profound at cerebral artery bifurcations than in adjacent branches or at extracranial bifurcations and (ii) such damage is initiated from the intima. The architecture of cerebral artery bifurcations will be examined in rabbits with aortic coarctation hypertension, atherosclerosis, or carotid ligation and from human autopsies. The focus will be on young adult male rabbits with appropriate controls. Quantitative stereological methods will be employed in order to comment on the role of endothelium, smooth muscle (SM) and the internal elastic lamina (IEL) in possible mechanical weakness of the arterial wall leading to atherosclerosis and aneurysm formation. The specific aims related to the structure of arterial bifurcations and medial gaps are (a) determine the patterns and precise orientation of endothelial and SM cells (b) map out the distribution, location and sizes of fenestrations in the IEL (c) quantitate any differences in proportional composition of the bifurcation wall compared to non-branching segments (d) determine the arrangement and interrelationship among cellular and acellular components of the intima. These structural parameters will be compared depending on (I) location (II) pressure or flow and (III) the existence of related pathology (atherosclerosis or aneurysms). The human cerebral circulation has a very high incidence of medial defects, minute aneurysms, and saccular aneurysms which may rupture resulting in subarachnoid hemorrhage, and arterial spasm. It is felt that a combination of congenital and/or acquired factors might give rise to aneurysm formation and rupture but there is as yet no accepted etiology. Stehbens (1) states "further information pertaining to the degenerative changes and hemodynamic stresses at arterial forks is the prerequisite for a more detailed outline of the pathogenesis of cerebral aneurysms". Only a quantitative stereological approach with mechanical analysis can provide this information. Revelance of experimental studies will be enhanced since the pattern of the rabbit and human cerebral vessels is very similar. Considering the incidence, mortality and morbidity of subarachnoid hemorrhage, it is important to answer fundamental questions about initial changes in bifurcation architecture which could be precursors for the pathogenesis of cerebral aneurysms which could lead to reevaluation of risk factors. More than half of Americans die from cardiovascular diseases of which most are related to the atherosclerotic process and this process is primarily due to familial hypercholesterolemia in less than 5% of cases (2). Cholesterol fed rabbits will provide data on the deposition of fat at carotid, cerebral and ear bifurcations. Yet altered blood pressure and flow may provide insights into the multifactorial and synergistic alterations which cause intimal cushions to form at the lateral angles and other sites about bifurcations. The same factors which cause abnormal permeability in small cerebral vessels may be a factor in intimal changes of larger bifurcations. Furthermore, since calcium entry blockers may have a protective effect against endothelial and SM damage, clinical doses of these drugs will be used to evaluate if they help prevent observed lesions or enhance their regression.