REDUCED THROMBOSIS AND RESTENOSIS AFTER LASER TREATMENT

申请者是一个多学科团队的成员，该团队长期 目的：提高激光治疗动脉粥样硬化的价值。 通过增加对激光组织的科学理解来治疗疾病 互动。已经完成的研究表明，某些激光 激光治疗的能力可能会将其临床价值扩展到 目前角色有限。 拟议的项目旨在发展这些有希望的发现。 在1987至1990年的NHLBI R01支持期间，以及在新的研究期间 自1990年迁至哈佛医学院以来，一直在进行这项工作。会的 关注激光可以去除动脉狭窄的初步发现 留下较少血栓形成的表面和血管收缩动脉 球囊血管成形术，激光可能促进局部基因治疗 以阻止细胞增殖和再狭窄。 具体目标1是定义激光组织相互作用的参数 通过评估影响血管组织的热和机械事件 血栓形成能力。房室分流模型将用于评估急性 犬血栓形成与动脉粥样硬化的慢性血栓形成 兔子。这将被测量为血小板沉降量和 激光和球囊治疗部位形成血栓。补充抗- 血栓形成机制也将受到测试。 具体目的2是确定激光在动脉粥样硬化兔体内是否会产生 比球囊血管成形术更少的血管收缩。血管舒缩反应 硝普钠、缓激肽、去甲肾上腺素、乙酰胆碱、5-羟色胺和 将测定加压素。 拟议项目的成功完成将提供一个目标 评估激光的这些潜在独特的改变能力 血管生物学和生理学行为。如果这些能力是 证实，它们在临床设计的激光系统中的开发 使用激光可以实现目前尚未实现的承诺 心理治疗。

The applicants are members of a multidisciplinary team whose long-term objective is to enhance the value of laser therapy for atherosclerotic disease by increasing scientific understanding of laser-tissue interactions. The research already completed suggest that certain laser capabilities may extend the clinical value of laser therapy beyond its currently limited role. The proposed project seeks to develop these promising findings obtained during NHLBI R01 support from 1987 to 1990, and during new studies conducted since relocation in 1990 to the Harvard Medical School. It will focus on the preliminary findings that lasers can remove arterial stenoses leaving a less thrombogenic surface and vasoconstrictive artery than balloon angioplasty, and that lasers may facilitate localized gene therapy to block cell proliferation and restenosis. Specific Aim 1 is to define the parameters of laser tissue interaction in vascular tissue by evaluating thermal and mechanical events which influence thrombogenicity. An AV shunt model will be used to assess acute thrombogencity in dogs and chronic thrombogenicity in atherosclerotic rabbits. This will be measured as the amount of platelet deposition and thrombus formation at laser and balloon treated sites. Supplemental anti- thrombotic regimes will also be tested. Specific Aim 2 is to determine in atherosclerotic rabbits if lasing creates less vasoconstriction than balloon angioplasty. Vasomotor response to nitorprusside, bradykinin norepinephrine, acetylcholine, serotonin and vasopressin will be determined. Successful completion of the proposed project will provide an objective assessment of these potential unique capabilities of lasers to alter vascular biologic and physiologic behavior. If these capabilities are substantiated, their exploitation in laser systems designed for clinical use could lead to realization of the currently unfulfilled promise of laser therapy.