LOCAL ANTITHROMBOTIC AGENTS IN MICROVASCULAR SURGERY

非常小的血管(直径2毫米)的吻合已经扩大。 外科医生重建缺失组织和血运重建的能力 或者移植器官。然而，显微外科操作施加了独特的 血管损伤，增加局部血栓形成和组织的风险 损失。这种情况下的血栓是富含血小板的，往往发生在或 在吻合口1-2厘米范围内，对 常规的抗血栓治疗。幸运的是， 这种血栓形成的时间相对较短(前30分钟最大)。 新近研制的抗体，当给予时，系统地结合到 循环中的血小板上的受体和防止黏附可能是强大的 足以防止显微吻合口的血小板沉积。不幸的是， 它们会延长出血时间，因此可能会增加罹患 术后出血。 相比之下，旨在破坏血小板与血小板黏附的局部疗法 显微吻合术因其特异性在理论上具有吸引力。 且系统性出血并发症的风险低。它特别是 在显微外科中很有吸引力，因为吻合口是 血栓形成，因为危险部位是开放的，可供 在吻合术完成时用局部试剂孵化。 显微吻合口有三个可能结合血小板的表面： 损伤/刺激的内皮；裸露的部位的内皮下层 损伤；缝合材料。还可以通过以下方式增强血小板粘附性 这些部位表面结合的凝血酶。使用新鲜的人体血管模型， 我们计划1。)测量已知结合的蛋白质的相对数量 三个表面(内皮细胞、内皮下细胞和 尼龙缝线)，在暴露于标准的、临床相关的 显微外科手术；2)测量每个人的血小板沉降量 这些表面在有或没有抗体的情况下掩盖了它们的 血小板的各自配体；基于2的结果。)， 将使用适当的抑制试剂来预防血小板 沉积到一个完整的显微吻合，其中包括所有的 临床相关模型中的各个表面。结合凝血酶 每个表面的活性将在等离子体暴露后进行测量，以 确定局部抑制凝血酶的补充需要 显微吻合术。基于这些数据，我们希望勾勒出一个具体的 可应用于微小数量的掩蔽分子的收集 在吻合时开放血管，从而降低 微吻合口血栓形成。

The anastomosis of very small blood vessels (< 2mm diameter) has expanded the ability of surgeons to reconstruct missing tissues and to revascularize or transplant organs. However, microsurgical manipulation imposes a unique vascular trauma which enhances the risk of local thrombosis and tissue loss. Thrombi in this setting are platelet-rich, tend to occur at or within 1-2cm of the anastomosis, and are remarkably resistant to conventional antithrombotic therapy. Fortunately, the risk interval for such thromboses is relatively short (maximal in the first thirty minutes). Recently developed antibodies which when given systematically bind to the receptors on circulating platelets and prevent adhesion may be powerful enough to prevent platelet deposition at microanastomoses. Unfortunately, they prolong the bleeding time and may thereby increase the risk of postoperative bleeding. In contrast, LOCAL therapy designed to disrupt platelet adhesion to a microanastomosis is theoretically attractive by virtue of its specificity and low risk of systemic bleeding complications. It is particularly attractive in microsurgery because the anastomosis is the prime site for thrombosis and because the site at risk is open and available for incubation with local reagents during completion of the anastomosis. A microanastomosis bears three potential surfaces which may bind platelets: the injured/stimulated endothelium; exposed subendothelium at sites of injury; and suture material. Platelet adhesion may also be augmented by surface-bound thrombin at these sites. Using a fresh human vessel model, we plan to 1.) measure the relative amounts of proteins known to bind platelets on each of the three surfaces (endothelium, subendothelium and nylon suture) after exposure of each to standard, clinically relevant microsurgical manipulations; 2.) measure platelet deposition to each of these surfaces in the presence and absence of antibodies which mask their respective ligands for platelets; and 3.) based on the results of 2.), the appropriate set of inhibitory reagents will be used to prevent platelet deposition to a completed microanastomosis, which incorporates all of the respective surfaces in a clinically relevant model. Bound thrombin activity on each surface will be measured after plasma exposure, to determine the supplemental need for local inhibition of thrombin at microanastomoses. Based on these data, we hope to outline a specific collection of masking molecules which may be applied in minute amounts to open vessels at the time of anastomosis, thereby reducing the risk of microanastomotic thrombosis.