BRAIN MICROEMBOLI DURING CARDIOPULMONARY BYPASS

体外循环期间的脑微栓塞

• 批准号: 3760895
• 负责人: DIXON M MOODY
• 金额: --
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3760895
• 关键词: X ray microscopy; aortic valve; basal ganglia; capillary; caudate nucleus; cerebellum; corpus striatum; electron microscopy; embolism; frontal lobe /cortex; heart /lung bypass; heart surgery; histochemistry /cytochemistry; human tissue; medial olfactory area; medulla oblongata; microscopy; mitral valve; parietal lobe /cortex; pons; postmortem; postoperative complications; scanning electron microscopy; skin; striated muscles; temporal lobe /cortex; thalamus; vasodilation

At least 79% of patients will have mild, moderate or severe intellectual dysfunction following surgery assisted by cardiopulmonary bypass (CPB). Although some suspect microemboli to be the etiologic agent causing this brain dysfunction, little objective evidence confirming the presence of emboli is reported with the most recent techniques of cardiac surgery. Recently, small capillary and arteriolar dilatations (SCADs) have been found in autopsy brains shortly after CPB irrespective of whether the membrane of bubble type of oxygenator was employed. These SCADs are probably the site of iatrogenic emboli (air, fat or some other material dissolved out by the solvents used in the preparation), and the vascular lumen remains fixed in a dilated or aneurysmal state after preparation for microvascular analysis. SCADs range in size from 10 mu m to 40 mu m, a size that lodges in the smallest vessels of the microvasculature, and they have been found in numbers that might be expected to cause subtle neurological dysfunction. SCADs have been found blocking 0.4% of the capillaries, but the larger ones blocking the 40-50 mu m system arterioles are believed to be more dangerous. Therefore, the outcome of surgery requiring CPB may be improved if the hundreds of thousands of these microemboli can be eliminated, but first their etiology must be established. A unique histochemical technique revealed the SCADs initially; it is also appropriate for their further quantification and characterization. The native alkaline phosphatase (AP) ectoenzyme, present in the endothelial plasma cell membrane of small arteries, arterioles, and capillaries, but not in veins or large arteries, is used to precipitate black lead sulfide salt in these structures. This histochemical technique is superior to injection techniques or stains of intravascular contents because it avoids artifacts of injection such as rupture and incomplete filling and loss of the stain at the cut surface of the tissue. More important for this proposal, one screening for small emboli, there is no possibility the SCADs have been injected artifactually during tissue preparation because nothing is injected at this stage, neither in fixation nor in staining. The AP histochemical technique also allows counterstaining of the background neural tissue with a variety of stains in the case of 100 mu m celloidin sections. This study will focus tightly on these SCADs to determine (1) their etiology, and (2) if they are clinically significant. The brains from non- surviving humans enrolled in Projects 1 and 2, will be examined in order to quantify the SCADs and to correlate their accumulation with the technical CPB conditions and the subjects' neurological outcome. Finally, we will quantify the SCADs in muscle and skin and correlate with 1) the accumulation of SCADs in the brains of non-surviving humans and, 2) postoperative neuropsychological testing in surviving patients in order to develop a surrogate for brain tissue in future studies aimed at reducing brain microemboli.

至少79%的患者将有轻度、中度或重度智力 体外循环(CPB)辅助手术后功能障碍。 尽管一些人怀疑微栓子是导致这种情况的病原体 脑功能障碍，几乎没有客观证据证实存在 栓子是最新的心脏外科手术技术的报告。 最近，小的毛细血管和小动脉扩张(SCAD) 在CPB后不久的尸检脑中发现，无论是否 采用鼓泡式膜式氧合器。这些伤痕是 可能是医源性栓子(空气、脂肪或其他物质)的部位 被制剂中使用的溶剂溶解)，以及血管 管腔在准备后仍处于扩张或动脉瘤状态 微血管分析。Scad的大小从10微米到40微米不等 位于微血管系统最小的血管中的大小，它们 被发现的数字可能会导致微妙的 神经功能障碍。已发现SCAD阻塞0.4%的 毛细血管，但较大的毛细血管阻塞40-50微米的系统小动脉 被认为更危险。因此，手术的结果 如果数十万人这样做，对CPB的要求可能会得到改善 微栓子是可以消除的，但首先必须确定其病因 已经成立了。 一种独特的组织化学技术最初发现了SCADS；它也是 适合于进一步量化和表征它们。这个 天然碱性磷酸酶(AP)胞外酶，存在于内皮细胞中 小动脉、小动脉和毛细血管的质膜，但 不存在于静脉或大动脉中，用于沉淀黑色硫化铅 这些结构中的盐。这种组织化学技术优于 注射技术或血管内内容物染色，因为它避免了 注射物的伪影，如破裂、充填不全和丢失 组织切割面上的污渍。对此更重要的是 建议，一次筛查小栓子，不存在SCADS 在组织准备过程中被人工注射，因为没有 在这个阶段注射，既不固定也不染色。美联社 组织化学技术也允许背景的反染色 100微米火棉胶中神经组织的各种染色 横断面。 这项研究将紧紧围绕这些SCAD来确定(1)其 病因学，以及(2)是否具有临床意义。来自非人类的大脑 登记在项目1和2中的幸存人类将接受检查，以便 量化SCAD，并将其积累与技术 体外循环条件和受试者的神经结局。最后，我们会 量化肌肉和皮肤中的毒素，并与1) 死亡者大脑中SCADS的积聚和，2) 术后存活患者的神经心理测试 在未来的研究中开发脑组织的替代品，旨在减少 脑微栓子。