PHYSICAL MECHANISMS OF TISSUE DAMAGE IN SWL

SWL 中组织损伤的物理机制

• 批准号: 6381517
• 负责人: James Alexander McAteer
• 金额: $ 23.28万
• 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 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6381517
• 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(SWL)已被证明是治疗上尿路结石非常有效的方法。虽然SWL被广泛认为是有效和安全的，但越来越多的人担心碎石术也会带来健康风险。现在有充分的证据表明，冲击波治疗会对肾脏造成创伤，主要是血管损伤，而冲击波治疗造成的急性损害可能会导致严重的长期并发症(例如，老年人新发的高血压)。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/或衍生新的患者方案是可行的，以使治疗更安全和更有效。然而，目前尚缺乏能够进行这种改进的基本信息：碎石机冲击波是如何导致组织损伤的尚不清楚；导致SWL肾脏损伤的物理机制尚未确定。本项目的目的是确定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验证这一假设，即SWL中的肾脏损害是由于碎石冲击波的两个显著特征：声空化和剪应力。这项修订提案有四个具体目标1和2，针对审查员的评论进行了广泛的修订。目的1将使用离体肾来确定空化引起的血管损伤的特征，确定空化以外的机械力是否是导致组织损伤的原因，并将测试当肾脏处于增加的流体静压下时，通过使用短波可以抑制SWL中的肾脏损伤的想法(以抑制空化检测和量化以表征血液中空化的开始和传播，并测试血管损伤依赖于冲击波诱导的肾血流量减少的想法。我们将评估血管系统支持空化的潜力，并确定空化如何受血管大小的影响。在目标3中，我们将使用培养的细胞模型来确定空化是否导致肾小管损伤，而在目标4中，我们将确定切应力如何导致SWL细胞损伤。该项目的主要目标是确定SWL中导致组织损伤的物理机制，以便开发出使SWL更安全的策略，以减少或消除导致不可逆转肾损伤的严重急性Schock波诱导的肾损伤。