REDUCED THROMBOSIS AND RESTENOSIS AFTER LASER TREATMENT

申请人是一个多学科团队的成员， 目的提高激光治疗动脉粥样硬化的价值 通过提高对激光组织的科学认识， 交互. 已经完成的研究表明，某些激光 这些能力可能会扩展激光治疗的临床价值 目前作用有限。 拟议的项目旨在发展这些有希望的研究结果， 在1987年至1990年的NHLBI R 01支持期间，以及在新研究期间， 自1990年搬迁到哈佛医学院以来进行。 它将 专注于激光可以去除动脉狭窄的初步发现 留下较少的血栓形成表面和血管收缩动脉， 球囊血管成形术，激光可以促进局部基因治疗 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， 血栓形成性 AV分流模型将用于评估急性 犬的血栓形成和动脉粥样硬化中的慢性血栓形成 家兔 这将被测量为血小板沉积的量， 激光和球囊治疗部位血栓形成。 补充抗- 还将测试血栓形成方案。 具体目标2是确定在动脉粥样硬化家兔中，激光是否产生 血管收缩比球囊血管成形术更少。 血管反应 硝普钠、缓激肽、去甲肾上腺素、乙酰胆碱、5-羟色胺和 将测定血管加压素。 成功完成拟议项目将提供一个目标， 评估这些潜在的独特能力的激光改变 血管生物学和生理学行为。 如果这些能力 证实，其开发的激光系统设计用于临床 使用激光器可能会实现目前尚未实现的激光器的承诺。 疗法

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.