EFFECT OF SHOCK WAVE LITHOTRIPSY ON RENAL FUNCTION/STRUCTURE IN THE PIG

冲击波碎石术对猪肾功能/结构的影响

• 批准号: 6570864
• 负责人: ANDREW P EVAN
• 金额: $ 29.59万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570864
• 关键词: biosensor device; disease /disorder proneness /risk; glomerular filtration rate; hemodynamics; hemorrhage; iatrogenic disease; inflammation; kidney circulation; kidney disorder; kidney function; kidney hypertrophy; kidney imaging /visualization; lithotripsy; medical complication; morphology; nephrolithiasis; nonhuman therapy evaluation; renal hypertension; renal ischemia /hypoxia; renal tubular transport; scars; swine; telemetry; transmission electron microscopy; vasoconstriction

The long term goal of the proposed research is to provide a scientific basis for establishing clinical conditions for the safest use of shock wave lithotripsy (SWL), while preserving its high level of efficacy. Recent findings from our group show that a clinical level of SWL induces a vascular insult within the kidney characterized by hemorrhage, inflammation and reduced perfusion. While the efficacy of SWL is not in question, these findings raise concerns about the long-term safety of SWL. The first step in addressing these concerns requires an understanding of the injury caused by SWL. This proposal will employ cellular, structural, molecular and functional approaches to characterize this injury under a variety of treatment conditions. The research will be conducted in pigs to: 1) Define the relationship between the size of the SWL-induced lesion and impairment of renal hemodynamics; 2) Determine the progression of the acute inflammatory/fibrogenic response after SWL-induced injury (collaboration with Project 2); 3) Identify the cause of the SWL-induced renal vasoconstriction; 4) characterize possible risk factors for SWL; 5) Determine the roles of acoustic cavitation and shear forces in SWL-induced tubular and vascular injury (collaboration with Projects 4 and 5). The relationship between lesion size and impaired renal hemodynamics will be determined with whole-kidney clearance and quantitative morphological techniques. The role of potential mediators of SWL-induced vasoconstriction will be determined with specific antagonists for appropriate receptors. The time course for renal fibrogenesis induced by SWL will be determined with the aid of radio-labeled markers (platelets, red cells, leukocytes, microspheres, etc), and gene expression of selected and potential novel cytokines and vasoactive compounds (endothelin, nitric oxide, thromboxane, etc). Sensitive hydrophones will be used to correlate intrarenal sites of acoustic cavitation with regions of renal injury, and arrays of miniaturized pressure transducers, implanted on kidneys, will determine the relationship of shear forces to the injury. The formation gained from these studies may lead to improved patient selection criteria or therapeutic interventions to limit or prevent SWL-induced renal injury.

这项研究的长期目标是提供一个科学的 建立最安全使用休克的临床条件的基础 波碎石术（SWL），同时保持其高水平的疗效。 我们小组最近的发现表明，临床水平的SWL诱导 肾内血管损伤，以出血为特征， 炎症和灌注减少。虽然SWL的功效并不明显， 这些发现引起了人们对SWL长期安全性的担忧。 解决这些问题的第一步需要了解 SWL造成的伤害。该提案将采用蜂窝，结构， 分子和功能的方法来表征这种损伤下， 各种治疗条件。这项研究将在猪身上进行 目的：1）定义SWL诱导的病变大小与 和肾血流动力学损害; 2）确定 SWL诱导损伤后的急性炎症/纤维化反应 （与项目2合作）; 3）确定SWL引起的 肾血管收缩; 4）描述SWL的可能风险因素; 5） 确定声空化和剪切力在SWL诱导的 肾小管和血管损伤（与项目4和5合作）。 病变大小与肾血流动力学受损之间的关系将 通过全肾清除率和定量形态学测定 技术. SWL诱导的潜在介质的作用 血管收缩将用特异性拮抗剂测定， 合适的受体。肾纤维化的时间进程 SWL将在放射性标记物（血小板， 红细胞、白细胞、微球等），以及所选择的 以及潜在的新型细胞因子和血管活性化合物（内皮素、一氧化氮 氧化物、血栓烷等）。灵敏的水听器将被用于关联 肾内声空化部位与肾损伤区域，以及 植入肾脏的微型压力传感器阵列将 确定剪切力与损伤的关系。形成 从这些研究中获得的信息可能会改善患者选择标准 或治疗性干预以限制或预防SWL诱导的肾损伤。