LOCAL ANTITHROMBOTIC AGENTS IN MICROVASCULAR SURGERY

非常小的血管（直径<2 mm）的吻合口扩大 外科医生重建缺失组织和重建血管的能力 或者移植器官 然而，显微手术操作施加了独特的 血管创伤，增加了局部血栓形成和组织 损失 这种情况下的血栓富含血小板，往往发生在或 在吻合口的1-2cm内，并且显著抵抗 常规抗血栓治疗。 幸运的是， 这种血栓形成相对较短（在最初的30分钟内最大）。 最近开发的抗体，当给予系统结合到 循环血小板上的受体并阻止粘附可能是强大的 足以防止血小板在微血管中沉积。 不幸的是， 它们会延长出血时间，从而增加 术后出血 与此相反，旨在破坏血小板粘附于血小板膜上的抗血小板治疗， 显微吻合术由于其特异性在理论上是有吸引力的 并且全身出血并发症的风险低。 显得尤为 在显微外科手术中很有吸引力，因为吻合是 血栓形成，并且因为风险部位是开放的， 在吻合术完成期间与当地试剂一起孵育。 显微吻合术具有三个可能结合血小板的潜在表面： 损伤/刺激的内皮;暴露的内皮下 损伤;和缝合材料。 血小板粘附也可能增加， 表面结合的凝血酶在这些网站。 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量 血小板在三个表面（内皮、内皮下和 尼龙缝线）暴露于标准品后，临床相关 显微外科操作; 2.）测量血小板沉积， 这些表面在存在和不存在抗体的情况下， 血小板的相应配体;和3.）基于2.）的结果，的 将使用适当的抑制试剂组来防止血小板聚集。 沉积到完成的显微吻合术，其中包括所有的 临床相关模型中的相应表面。 结合凝血酶 将在等离子体暴露后测量每个表面上的活性， 确定凝血酶局部抑制的补充需要， 显微镜检查 基于这些数据，我们希望能勾勒出一个具体的 掩蔽分子的集合，其可以以微小的量施加， 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.