LASER IRRADIATION AND VASCULAR REACTIVITY II

激光照射和血管反应性 II

• 批准号: 2219631
• 负责人: Jeffrey Isner
• 金额: $ 20.52万
• 依托单位: STEWARD ST. ELIZABETH'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2219631
• 关键词: analgesics; argon; atherosclerosis; cimetidine; cyclic GMP; diltiazem; drug metabolism; indomethacin; ketamine; laboratory rabbit; laser therapy; muscle relaxation; particle beam; phentolamine; prazosin; propranolol; pulse pressure wave; pulse radiolysis; radiation therapy; radiopharmacology; vascular smooth muscle; vasomotion

The series of experiments outlined in this Proposal has been designed to systematically investigate the fundamental mechanisms responsible for laser-induced alterations of vascular tone. Preliminary data resulting from experiments carried out in our Laboratories during the first three years of this Grant, together with data from other Laboratories and established paradigms for physiologic alteration of vascular smooth muscle (VSM) tone have led us to formulate a series of working hypotheses. These hypotheses and the experimental protocols by which they will be tested are organized according to two Specific Aims. The experiments described under Specific Aim 1 have been designed to identify the specific intra-cellular processes which mediate laser-induced relaxation of VSM. Preliminary studies suggest that the heme moiety of cytosolic guanylate cyclase (GC) may serve as a chromophore to promote absorption of laser light, thereby activating GC, resulting in the production of 3',5' cyclic guanosine monophosphate (cGMP) and relaxation of VSM. Accordingly, we will begin by investigating the principal hypothesis that laser-induced photorelaxation of VSM is the result of increased production of cGMP. The experiments described un Specific Aim 2 are designed to identify the specific intracellular processes which mediate laser-induced contraction of VSM. Our approach to this issue will begin with consideration of the hypothesis that laser-induced vasoconstriction results from the breakdown of phosphatidylinositol 4,5-biphosphate (PIP2), releasing inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DG), thereby producing vasoconstriction of VSM. Finally, experiments performed previously in our Laboratory have demonstrated that heat generated under certain circumstances of laser irradiation is a potent stimulus for vasoconstriction of VSM. We will therefore test the hypothesis that intra- cellular processes mediating laser-induced vasoconstriction result in part from heat and/or acoustic transients generated during laser irradiation. Preliminary work currently in progress in our Laboratory suggests that these investigations may yield promising insights into the fundamental basis for laser-induced alterations in vasomotor reactivity, and at the same time suggest meaningful ways that these observations may be incorporated into clinical practice.

该提案中概述的一系列实验已设计为 系统地研究负责的基本机制 激光引起的血管张力改变。 产生的初步数据 从在前三个实验室进行的实验 该赠款的多年，以及其他实验室的数据以及 建立的血管平滑肌生理改变范例 （VSM）语气使我们提出了一系列工作假设。 这些 假设和将测试的实验方案是 根据两个具体目标组织。 特定目标1所述的实验已设计为 确定介导激光诱导的特定细胞内过程 VSM的放松。 初步研究表明血红素部分 胞质鸟苷酸环化酶（GC）可以用作发色团来促进 吸收激光，从而激活GC，导致 生产3'，5'环鸟嘌呤一磷酸（CGMP）和放松 VSM。 因此，我们将首先调查主要假设 激光诱导的VSM的光延迟是增加的结果 CGMP的生产。 所描述的特定目标2的实验是 旨在确定介导的特定细胞内过程 激光诱导的VSM收缩。 我们解决这个问题的方法将开始 考虑到激光引起的血管收缩的假设 磷脂酰肌醇4,5-二磷酸（PIP2），磷脂酰肌醇的分解，结果 释放肌醇1,4,5-三磷酸（IP3）和二酰基甘油（DG）， 从而产生VSM的血管收缩。 最后，实验进行了 以前在我们的实验室中表明，在 激光照射的某些情况是对 VSM的血管收缩。 因此，我们将检验以下假设 介导激光引起的血管收缩的细胞过程部分结果 从激光照射期间产生的热量和/或声学瞬变。 我们实验室目前正在进行的初步工作表明 这些调查可能会产生对基本的有希望的见解 激光诱导的血管肌反应性改变的基础，在 同一时间暗示了这些观察可能是有意义的方法 纳入临床实践。

项目成果

In vivo assessment of vascular pathology resulting from laser irradiation. Analysis of 23 patients studied by directional atherectomy immediately after laser angioplasty.

激光照射引起的血管病理学的体内评估。

• DOI: 10.1161/01.cir.85.6.2185
• 发表时间: 1992
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Isner,JM;Rosenfield,K;White,CJ;Ramee,S;Kearney,M;Pieczek,A;LangevinJr,RE;Razvi,S
• 通讯作者: Razvi,S

Arterial gene transfer to rabbit endothelial and smooth muscle cells using percutaneous delivery of an adenoviral vector.

使用经皮递送腺病毒载体将动脉基因转移至兔内皮细胞和平滑肌细胞。

• DOI: 10.1161/01.cir.90.4.1648
• 发表时间: 1994
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Steg,PG;Feldman,LJ;Scoazec,JY;Tahlil,O;Barry,JJ;Boulechfar,S;Ragot,T;Isner,JM;Perricaudet,M
• 通讯作者: Perricaudet,M

Noninvasive assessment of peripheral vascular disease by color flow Doppler/two-dimensional ultrasound.

通过彩色血流多普勒/二维超声对周围血管疾病进行无创评估。

• DOI: 10.1016/0002-9149(89)90472-4
• 发表时间: 1989
• 期刊: The American journal of cardiology
• 作者: Rosenfield,K;Kelly,SM;Fields,CD;Pastore,JO;Weinstein,R;Palefski,P;LangevinJr,RE;Kosowsky,BD;Razvi,S;Isner,JM
• 通讯作者: Isner,JM

Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium.

• DOI: 10.1161/01.cir.95.4.1030
• 发表时间: 1997-02
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Rien van der Zee;T. Murohara;Zhengyu Luo;F. Zollmann;J. Passeri;C. Lekutat;J. Isner

Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia.

• 发表时间: 1994-11
• 期刊: Circulation
• 影响因子: 37.8
• 作者: S. Takeshita;L. Q. Pu;L. Stein;A. Sniderman;S. Bunting;N. Ferrara;J. Isner;J. Symes;J. Symes