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Evaluation of shock wave lithotripsy injury in the pig using a narrow focal zone lithotriptor

机译：利用窄焦区Lithotriptor评估猪的冲击波碎石曲线损伤

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OBJECTIVE class="unordered" style="list-style-type:disc">To assess renal injury in a pig model after treatment with a clinical dose of shock waves using a narrow focal zone (≈ 3 mm) lithotriptor (Modulith SLX, Karl Storz Lithotripsy).MATERIALS AND METHODS class="unordered" style="list-style-type:disc">The left kidney of anaesthetized female pigs were treated with 2000 or 4000 shock waves (SWs) at 120 SWs/min, or 2000 SWs at 60 SWs/min using the Storz SLX.Measures of renal function (glomerular filtration rate and renal plasma flow) were collected before and 1 h after shock wave lithotripsy (SWL) and the kidneys were harvested for histological analysis and morphometric quantitation of haemorrhage in the renal parenchyma with lesion size expressed as a percentage of functional renal volume (FRV).A fibre-optic probe hydrophone was used to determine acoustic output and map the focal width of the lithotriptor.Data for the SLX were compared with data from a previously published study in which pigs of the same age (7–8 weeks) were treated (2000 SWs at 120 or 60 SWs/min) using an unmodified Dornier HM3 lithotriptor.RESULTS class="unordered" style="list-style-type:disc">Treatment with the SLX produced a highly focused lesion running from cortex to medulla and often spanning the full thickness of the kidney. Unlike the diffuse interstitial haemorrhage observed with the HM3, the SLX lesion bore a blood-filled core of near-complete tissue disruption devoid of histologically recognizable kidney structure.Despite the intensity of tissue destruction at the core of the lesion, measures of lesion size based on macroscopic determination of haemorrhage in the parenchyma were not significantly different from kidneys treated using the HM3 (2000 SWs, 120 SWs/min: SLX, 1.86 ± 0.52% FRV; HM3, 3.93 ± 1.29% FRV).Doubling the SW dose of the SLX from 2000 to 4000 SWs did not significantly increase lesion size. In addition, slowing the firing rate of the SLX to 60 SWs/min did not reduce the size of the lesion (2.16 ± 0.96% FRV) compared with treatment at 120 SWs/min, as was the case with the HM3 (0.42 ± 0.23% FRV vs 3.93 ± 1.29% FRV).Renal function fell significantly below baseline in all treated groups but was similar for both lithotriptors.Focal width of the SLX (≈ 2.6 mm) was about one-third that of the HM3 (≈ 8 mm) while peak pressures were higher (SLX at power level 9: P+ ≈ 90 MPa, P− ≈ −12 MPa; HM3 at 24 kV: P+ ≈ 46 MPa, P−≈−8 MPa).CONCLUSIONS class="unordered" style="list-style-type:disc">The lesion produced by the SLX (narrow focal width, high acoustic pressure) was a more focused, more intense form of tissue damage than occurs with the HM3.Slowing the SW rate to 60 SWs/min, a strategy shown to be effective in reducing injury with the HM3, was not protective with the SLX.These findings suggest that the focal width and acoustic output of a lithotriptor affect the renal response to SWL. class="kwd-title">Keywords: shock wave lithotripsy, renal injury, narrow focal zone class="head no_bottom_margin" id="S5title">INTRODUCTIONRenal injury is an unfortunate but expected consequence of shock wave lithotripsy (SWL). All patients experience at least mild haematuria, some develop subcapsular or perinephric haematomas, and in rare cases excessive bleeding can develop, requiring intervention [–]. SWL injury has not been well studied in patients but there is a wealth of information describing the renal response to SWs in experimental animals. The most thorough characterization has been conducted in the pig model where the severity of tissue damage and size of the haemorrhagic lesion are dependent on many factors, including treatment settings for power and shock wave (SW) rate, the sequence of SW delivery, the number of SWs and the size of the kidney [–]. This work in assessing treatment variables has helped to estimate the potential for injury in the clinical setting and has revealed treatment strategies that significantly reduce tissue damage [,,–]. Thus, there is a growing understanding of how treatment settings contribute to injury in SWL. However, little has been done in a systematic way to compare the injuries produced by different lithotriptors.Lithotriptors are not all the same. The SWs of all lithotriptors have similar features, but the acoustic output and dimensions of the focal zone produced by different machines can be very different []. Focal width is a critical feature of a lithotriptor and in working terms describes how tightly SW energy is focused in the patient. Focal width is important because it affects the mechanisms at play in stone breakage. Shear stress contributing to stone breakage is enhanced when the focal width is wider than the stone [,]. Also, since respiratory motion moves the stone in and out of the focal zone, a lithotriptor with larger focal width has an improved chance of hitting the target []. Indeed, patient studies have suggested that focal width can affect outcomes with lower stone-free rates for narrow focal width lithotriptors [–]. Focal width has also been implicated in SWL injury, with the suggestion of an increased occurrence of adverse effects with narrow focal width machines [,].The focal widths of current lithotriptors cover a broad range, from ≈ 2.1 mm (Wolf Piezolith P3000) to ≈ 20 mm (LithoGold LG-380). Most machines are reported have a focal width of about 6–10 mm and it is not uncommon to find considerable variance for the values reported for a given machine. For example, reported values of focal width for the unmodified Dornier HM3 lithotriptor (Dornier Medical Systems, Kennesaw, GA, USA) run from ≈ 8 to ≈ 12 mm, the difference being due to how the measurements were conducted [href="#R14" rid="R14" class=" bibr popnode">14,href="#R25" rid="R25" class=" bibr popnode">25]. Accurate measures require rigorous mapping of the pressure field with a fibre-optic probe hydrophone and this is not an assessment often performed beyond the characterization required for the licensing and approval of a new lithotriptor [href="#R26" rid="R26" class=" bibr popnode">26]. id="P17">The Storz Modulith SLX (Karl Storz Lithotripsy, Atlanta, GA, USA) is an electromagnetic lithotriptor that has gained considerable popularity within the urology community. This machine emerged during the wave of technical development spurred by interest in making SWL an anaesthesia-free procedure. Since discomfort during SWL is due largely to cutaneous sensation, the strategy used by many manufacturers was to widen the aperture of the shock source to spread the area of contact between the acoustic pulse and the body. This reduced pain at the skin but also narrowed the focal zone [href="#R14" rid="R14" class=" bibr popnode">14]. The SLX has a focal width of only ≈ 3 mm and produces higher acoustic pressures (P+≈ 90 MPa) than broader focal width machines (i.e. LG-380: FW ≈ 20 mm, P+≈ 20 MPa; XiXin CS2012: FW ≈ 18 mm, P+ ≈ 17 MPa; HM3: FW ≈ 8 mm, P+≈ 40 MPa) [href="#R26" rid="R26" class=" bibr popnode">26,href="#R27" rid="R27" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_276741378">27]. id="P18" class="p p-last">As kidney injury has not been adequately assessed for a narrow focal zone lithotriptor, we used the pig model to characterize the renal response to SWs for the SLX. SWs were administered under conditions that simulated clinical SWL at settings for SW number, power level and SW rate that have been reported for treating patients using this lithotriptor [href="#R28" rid="R28" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_276741381">28]. Data for morphology, lesion size and renal function were compared with similar, previously published data for pigs treated using the Dornier HM3 [href="#R10" rid="R10" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_276741359">10]. The study included assessment of the renal response to slow SW rate, a treatment strategy shown to protect against renal trauma in the pig model [href="#R9" rid="R9" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_276741355">9,href="#R10" rid="R10" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_276741364">10].
机译：目标 class =“无序”style =“list-style-type：disc”> <！ - 列表 - 行为=无序前缀-word = mark-type = disc max-label-size = 0 - >
  • 使用狭窄的焦点区域（≈3mm）leithotor（Modulith SLX，Karl Storz Lithotripsy）进行临床剂量的冲击波治疗猪模型中的肾模型中的肾脏损伤。 材料和方法< UL Class =“无序”样式=“列表样式类型：光盘”> <！ - 列表行为=无序前缀-Word = Mark-Type = Dist Max-Label-Size = 0 - >
  • 使用Storz SLX在60瓦斯/分钟的60瓦斯/分钟内用2000或4000次冲击波（SWS）处理麻醉的母猪的左肾。
  • 肾功能的测量（肾小球过滤在冲击波型（SWL）之前和1小时之前收集速率和肾脏等离子体流动，并收获肾脏的组织学分析和肾脏实质中出血的形态定量，病变大小表示为功能性肾脏体积（FRV）的百分比。 光纤探针水听器测定声学输出并映射锂替司宫的焦距。与先前公布的研究中的数据进行了比较了SLX的数据，其中相同年龄的猪（7使用未修改的Dornier HM3 LithotRiptor处理-8周）（2000 SWS在120或60 SWS / min）。 结果 <！ - 列表行为=无序前缀-Word = mark-type = disc max-label-size = 0 - > 用SLX处理产生高度聚焦的病变，从皮质到髓质，经常跨越肾脏的全厚度。与用HM3观察到的弥漫性间质出血不同，SLX病变钻孔含有近乎完全的组织破坏的血液填充核心，其具有组织学可识别的肾结构。
  • 尽管核心的组织破坏强度病变，基于宏观测定疗法测定的病变尺寸与使用HM3（2000WS，120W​​WS / MIN：SLX，1.86±0.52％FRV; HM3，3.93±1.29％FRV）没有显着差异。HM3，3.93±1.29％FRV）没有显着差异。
  • 将SLX的SW剂量从2000到4000倍加倍，没有显着增加病变尺寸。此外，减缓SLX至60WS / min的烧制率与120SWS / min的处理相比，在120SWS / min的处理中，不降低病变（2.16±0.96％FRV）的尺寸，如HM3的情况（0.42±0.23 ％FRV与3.93±1.29％FRV）。
  • 肾功能在所有治疗组中大幅下降低于基线，但对于狼人冠状镜同样相似。
  • SLX的焦距（≈2.6mm HM3（≈8mm）的三分之一约为，而峰值压力较高（功率等级为9：P +≈90MPa，P-≈~~10MPa; HM3在24 kV：P +≈46MPa，p -I≈Acio8 MPA）。 结论 class =“无序”style =“list-style类型：disc”> <！ - list-theopear =无序前缀-Word =mark-type =光盘max-label-size = 0 - > 由SLX产生的病变（狭窄的焦距，高声压）是一种比HM3的更加聚焦，更强烈的组织损伤形式。
  • 减慢了SW速率60SWS / min，显示有效地减少HM3损伤的策略并不与SLX保护。
  • 这些研究结果表明，Lithotriptor的焦距和声学输出影响肾反应SWL。 class =“kwd-title”>关键词：冲击波碎石术，肾损伤，窄焦区类=“head no_bottom_margin”id =“s5title”>介绍肾损伤是一个不幸的人，但冲击波碎石术（SWL）的预期后果。所有患者体验至少温和的血尿，有些患有亚面脓疱疮血管瘤，并且在极少数情况下，过量出血可以发育，需要干预[ - ]。 SWL损伤在患者中尚未得到很好的研究，但是有丰富的信息描述了对实验动物的SWS的肾反应。在猪模型中进行了最彻底的表征，其中组织损伤和出血性病变的大小的严重程度取决于许多因素，包括用于电源和冲击波（SW）速率的处理环境，SW递送顺序，数字跨越肾小度的大小[ - ]。在评估治疗变量方面的工作有助于估计临床环境中受伤的可能性，并揭示了显着降低组织损伤[，]的治疗策略。因此，越来越高兴地理解如何在SWL中有助于伤害。然而，很少是以系统的方式进行比较不同的Lithotriptors产生的伤害.Lithotriplor并不一样。所有Lithotriptors的SWS都有类似的特征，但不同机器产生的焦区的声学输出和尺寸可能非常不同[]。焦距是Lithotriptor的关键特征，并且在工作方面描述了患者在患者中侧重于SW能量的紧密能量。焦距很重要，因为它会影响石头破损的游戏机制。当焦距比石头宽度宽的剪切应力增加到石头破损的剪切应力是增强的。而且，由于呼吸运动将石头移入并出焦点区域，因此具有较大焦距的碎石梯度具有击中目标的可能性提高了[]。实际上，患者研究表明，焦距可以影响窄焦距Lithotriptors的较低石头速率的结果[ - ]。焦距也涉及SWL损伤，提出了与窄焦宽机器的不利影响发生的建议。电流碎石梯的焦距覆盖了广泛的范围，从≈2.1mm（狼Pizoleith p3000）到≈20mm（Lithogold LG-380）。报告大多数机器的焦距约为6-10毫米，并且对于给定机器报告的值并不罕见。例如，报告了未经修改的Dornier HM3 Lithotriptor（Dornier Medical Systems，Kennesaw，Ga，USA）的焦距的值从≈8到≈12mm，差异是由于如何进行测量[href =“ #R14“RID =”R14“类=”BIBR POPNODE“> 14 ，HREF="#R25"IV="r25"类=”bibr popnode"> 25 “。准确的措施要求使用光纤探头水听的压力场严格映射，并且这不是通常进行的评估，这些评估通常超出了新的leithotriptor的许可和批准所需的特征[href =“＃r26”摆脱=“r26 “类=”BIBR POPNODE“> 26 ]。

    Storz Modulith SLX（Karl Storz Lithotripsy，Atlanta，Ga，USA）是一种电磁型Lithotriptor，它在泌尿外科内获得了相当大的普及社区。这台机器在兴趣的技术开发浪潮中出现，使SWL无麻醉程序。由于SWL期间的不适由于很大程度上是针对性的感觉，许多制造商使用的策略是扩大震源的孔径，以扩散声脉冲和主体之间的接触区域。这种皮肤疼痛减少，但也缩小了焦点[href="#r14" rid="r14" class="bibr popnode"> 14 ]。 SLX的焦距仅为≈3mm，比更广泛的焦宽机（即LG-380：FW≈20mm，p +≈20MPa; XIXIN CS2012：FW≈18mm：FW≈18mm，产生更高的声压（P +≈90MPa） ，p +≈17mpa; hm3：fw≈8mm，p +≈40mpa）[href="#r26"id="r26" class="bibr popnode"> 26 ，href =“ #R27“RID =”R27“Class =”BIBR POPNODE TAG_HOTLINK TAG_TOOLTIP“ID =”__ TAG_276741378“> 27 ”。 id =“p18”类=“p p-lall”>如肾脏损伤尚未对狭窄的焦点区Lithotriptor进行充分评估，我们使用猪模型来表征对SLX的SWS的肾反应。在据报道使用该leithotriptor治疗患者的SW数量，功率水平和SW速率的条件下施用SWS，以便使用该Lithotriptor [href =“＃r28”RID =“R28”Class =“Bibr Popnode tag_hotlink tag_tooltip“id =”__ tag_276741381“> 28 10 ]。该研究包括评估对SW速率缓慢的肾反应，视证明的治疗策略用于防止猪模型中的肾创伤[href =“#r9”RID =“R9”类=“BIBR POPNODE TAG_HOTLINK TAG_TOOLTIP”ID = “__tag_276741355”> 9 ，href="#r10"id="r10"类="bibr popnode tag_hotlink tag_tooltip" id="_tag_276741364"> 10

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