PHYSICAL MECHANISMS OF TISSUE DAMAGE IN SWL

SWL 中组织损伤的物理机制

• 批准号: 6635148
• 负责人: James Alexander McAteer
• 金额: $ 26.29万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635148
• 关键词: biophysics; human therapy evaluation; kidney disorder; laboratory rabbit; laboratory rat; lithotripsy; mechanical stress; tissue /cell culture

Shock wave lithotripsy (SWL) has proven to be very effective treatment for the elimination of upper urinary tract stone. Although SWL is widely regarded as effective and safe there is growing concern that lithotripsy also poses a health risk. It is now well documented that SWL causes trauma to the kidney, dominated by vascular injury, and that the acute damage caused by shock wave treatment can lead to serious long-term complications in some individuals )e.g.new onset hypertension in the elderly). Thus, the safety of SWL is in question. It is feasible to improve SWL, to change the properties of lithotripter shock waves and/or derive new patient protocols to make treatment safer and more effective. However, basic information is missing that would allow such improvements to be made: how lithotripter schock waves cause tissue damage is unknown; the physical mechanisms responsible for kidney damage in SWL have yet to be determined. The objective of this project is to determine the physical mechanisms of tissue damage in SWL. We propose a biophysics- based in vitro approach to test the hypothesis that kidney damage in SWL is due to two prominent features of lithotripter shock waves: acoustic cavitation and shear stress. This revised proposal has four Specific Aims 1 and 2 have undergone extensive revisions in response to reviewers' commetns. Aim 1 will use isolated kidneys to characterize vascular trauma due to cavitation, determine if mechanical forces other than cavitation contribute to tissue damage, and will test the idea that kidney damage in SWL can be inhibited by administering SW's when the kidney is under increased hydrostatic pressure (to suppress cavitation detection and quantitation to characterize the inception and propagation of cavitation in blood, and test the idea that vascular damage is dependent upon a shock wave- induced reduction in the rate of renal blood flow. We will assess the potential for the vasculature to support cavitation and determine how cavitation is affected by vessel size. In Aim 3 we will use cultured cell models to determine if cavitation is responsible for damage to renal tubules, and in Aim 4 we will determine how shear stress contributes to SWL cell injury. The main goal of this project is to determine the physical mechanisms that are responsible for tissue damage in SWL, so that strategies can be developed to make SWL safer, to reduce or eliminate the significant acute schock wave-induced renal trauma that leads to irreversible kidney damage.

冲击波碎石术（SWL）已被证明是消除上尿路结石非常有效的治疗方法。尽管 SWL 被广泛认为有效且安全，但人们越来越担心碎石术也会带来健康风险。 现在有充分证据表明，SWL 会对肾脏造成损伤，主要是血管损伤，并且冲击波治疗引起的急性损伤可能会导致某些个体出现严重的长期并发症（例如老年人新发高血压）。因此，SWL 的安全性受到质疑。 改善 SWL、改变碎石机冲击波的特性和/或制定新的患者方案以使治疗更安全、更有效是可行的。 然而，缺乏能够进行此类改进的基本信息：碎石机冲击波如何引起组织损伤尚不清楚；导致 SWL 肾损伤的物理机制尚未确定。该项目的目的是确定 SWL 中组织损伤的物理机制。 我们提出了一种基于生物物理学的体外方法来检验以下假设：SWL 中的肾损伤是由碎石机冲击波的两个突出特征造成的：声空化和剪切应力。该修订后的提案有四个具体目标 1 和 2 根据审稿人的意见进行了广泛的修订。目标 1 将使用离体肾脏来表征空化引起的血管损伤，确定空化以外的机械力是否会导致组织损伤，并将测试当肾脏处于增加的静水压时，可以通过施用 SW 来抑制 SWL 中的肾脏损伤的想法（以抑制空化检测和定量来表征血液中空化的开始和传播，并测试血管损伤取决于冲击波的想法） 导致肾血流量减少。 我们将评估脉管系统支持空化的潜力，并确定血管尺寸如何影响空化。 在目标 3 中，我们将使用培养细胞模型来确定空化是否会导致肾小管损伤，在目标 4 中，我们将确定剪切应力如何导致 SWL 细胞损伤。该项目的主要目标是确定造成 SWL 组织损伤的物理机制，以便制定策略 开发的目的是使 SWL 更安全，减少或消除严重的急性冲击波引起的肾损伤，从而导致不可逆的肾损伤。