Sarica Kemal, Sari Ibrahim, Balat Ayşe, Erbağci Ahmet, Yurtseven Cihanser, Yağci Faruk, Karakök Metin
Department of Urology, Sahinbey Medical Center, University of Gaziantep, Medical School, 27070 Kolejtepe/Gaziantep, Turkey.
Urol Res. 2003 Aug;31(4):267-71. doi: 10.1007/s00240-003-0323-4. Epub 2003 Jun 26.
Despite its safety and efficacy, the traumatic effects of high-energy shock waves (HESW) on renal morphology and function during long-term follow-up have yet to be elucidated. Although the main target of shock waves is the stone located in the kidney, the surrounding tissue and other organs are also subjected to trauma during this procedure. In contrast to renal blood flow evaluation after shock wave treatment, ischemic development, causing varying degrees of damage at the tissue level, has not been well evaluated. The renoprotective peptide adrenomedullin (AM) is a potent vasorelaxing, natriuretic and cell growth modulating peptide, which is thought to act as an autocrine/paracrine regulator in renal glomeruli and tubules. In this experimental study, renal parenchymal AM levels were assessed in an attempt to evaluate the effect of HESW on the tissue levels of this peptide, which may be responsible for the regulation of ischemia induced by extracorporeal shock wave lithotripsy(ESWL), in a rabbit model. Thirty white New Zealand rabbits, each weighing 3-5 kg were used. The animals were divided into three main groups, and varying numbers of shock waves (1000, 1500, 2000) were applied under fluoroscopic localization to the same kidney of all animals. Ketamine HCl anesthesia was administered (15-20 mg/kg) and all of the procedures were performed with a Multimed 2000 lithotriptor. Untreated contralateral kidneys were evaluated as controls. Following HESW application, the treated and untreated kidneys of each animal were removed through bilateral flank incisions under ketamine HCl anesthesia after 24 h and 7 days, respectively. Tissue AM levels were assessed with immunohistochemistry. During the early follow-up period (24 h), both treated and untreated kidneys showed a moderate to high degree of AM positivity. The number of tubules stained with AM increased as the number of shock waves increased and the expression of this protein became evident, possibly due to a higher degree of tissue damage. Additionally, a limited degree of AM positivity was noted in the contralateral kidneys although this was not as evident as the positivity seen in the treated kidneys. Assessment of tissue AM levels during late follow-up (7 days) in both kidneys demonstrated a moderate or limited degree of positivity in the treated kidneys. Limited or no positivity could be demonstrated in the contralateral kidneys at this time. Taking the certain traumatic effects of HESW, which causes transient ischemia during ESWL, into account, we conclude that the application of HESW results in a transient decrease in renal perfusion, causing ischemic injury in treated as well as in contralateral (untreated) kidneys. This ischemic event lasts for a short time and seemed to be dose- and time-dependent. Increased tissue levels of AM appear to be a potential defence against ESWL induced ischemia.
尽管高能冲击波（HESW）具有安全性和有效性，但其在长期随访过程中对肾脏形态和功能的创伤性影响尚未阐明。虽然冲击波的主要靶点是位于肾脏的结石，但在此过程中周围组织和其他器官也会受到创伤。与冲击波治疗后的肾血流评估不同，导致组织水平不同程度损伤的缺血发展情况尚未得到充分评估。肾保护肽肾上腺髓质素（AM）是一种强效的血管舒张、利钠和调节细胞生长的肽，被认为在肾小体和肾小管中作为自分泌/旁分泌调节剂发挥作用。在本实验研究中，通过评估兔模型中肾实质AM水平，试图评价HESW对该肽组织水平的影响，该肽可能负责调节体外冲击波碎石术（ESWL）诱导的缺血。选用30只体重3 - 5千克的白色新西兰兔。将动物分为三个主要组，在荧光透视定位下对所有动物的同一侧肾脏施加不同数量的冲击波（1000、1500、2000）。给予盐酸氯胺酮麻醉（15 - 20毫克/千克），所有操作均使用Multimed 2000碎石机进行。未处理的对侧肾脏作为对照。在施加HESW后，分别在24小时和7天后，在盐酸氯胺酮麻醉下通过双侧胁腹切口切除每只动物处理过的和未处理的肾脏。用免疫组织化学方法评估组织AM水平。在早期随访期（24小时），处理过的和未处理的肾脏均显示中度至高度的AM阳性。随着冲击波数量的增加，AM染色的肾小管数量增加，并且这种蛋白质的表达变得明显，这可能是由于更高程度的组织损伤。此外，在对侧肾脏中也观察到有限程度的AM阳性，尽管不如处理过的肾脏中那么明显。在晚期随访（7天）时对双侧肾脏组织AM水平的评估显示，处理过的肾脏呈中度或有限程度的阳性。此时对侧肾脏显示有限或无阳性。考虑到HESW在ESWL期间会导致短暂缺血的一定创伤性影响，我们得出结论，HESW的应用会导致肾灌注短暂下降，在处理过的肾脏以及对侧（未处理）肾脏中造成缺血性损伤。这种缺血事件持续时间较短，似乎与剂量和时间有关。AM组织水平的升高似乎是对ESWL诱导的缺血的一种潜在防御。
