Jakobsen Jørn Skibsted
Department of Urology, University Hospital of Southern Denmark, Sdr. Boulevard 29, 5000 Odense C, Denmark.
Dan Med J. 2013 May;60(5):B4642.
The experiments performed in this PhD thesis were conducted at the Institute of Experimental Surgery, Skejby Hospital, Aarhus, Denmark and at the Laboratory of Animal Science, Odense University Hospital, Denmark. The thesis is based on 3 peer review articles published in international journals and a review. Diagnostic or therapeutic endoscopic upper urinary tract procedures are usually characterised as minimal invasive procedures and associated with a low complication rate. Most often fever or pain are seen and sometimes septicaemia. However, mucosa lesion or even ureteric ruptures are known complications. Research has suggested that high renal pelvic pressures generated during these procedures, might contribute to per-/postoperative complications seen, and even possible renal parenchymal damage. Nevertheless, local administration (endoluminal) of a relaxant drug has not previously been tried in order to lower renal pelvic pressure. The purposes of this thesis were to examine the effect of local administration (endoluminal) of the nonspecific β-adrenergic agonist ISOproterenol (ISO) on: 1) The normal pressure flow relation in porcine ureter, 2) The effect of endoluminal ISO perfusion during flexible ureterorenoscopy, 3) The pressure flow relation during semirigid ureterorenoscopy and 4) The cardiovascular system. Among other receptor-types β-adrenergic receptor are located in the upper urinary tract and the activation thereof mediates smooth muscle relaxation. We have shown - in an animal experimental model - that ISO added to the irrigation fluid had significant impact on the renal pelvic pressures generated during upper urinary tract endoscopy. ISO significantly and dose dependently reduced the normal pressure flow relations by approximately 80% without concomitant cardiovascular side effects or measurable plasma levels of ISO. During flexible ureterorenoscopy 0.1 µg/ml ISO added to the irrigation fluid significantly reduced renal pelvic pressure during perfusion compared to saline perfusion alone. Pressures obtained during ISO perfusion were kept below the critical pressure for intrarenal reflux. The pressure flow relation during semirigid ureterorenoscopy was linear and ISO reduced pelvic pressure significantly, but not below the critical level for intrarenal reflux. In conclusion, ISO 0.1 µg/ml added to the irrigation fluid during endoscopic procedures was safe in this porcine model. Alongside this thesis, we have demonstrated the relaxing potency of 0.1 µg/ml ISO added to the irrigation fluid in a human trial and found it safe. Future research in this area, especially randomized clinical trials, regarding the relaxing potency, complication rates, pain episodes etc. should be evaluated. The addition of a relaxant drug to the irrigation fluid may prove to favour therapeutic or diagnostic endoscopic procedures in the upper urinary tract in the future.
本博士论文中的实验是在丹麦奥胡斯市斯凯比医院实验外科研究所和丹麦欧登塞大学医院动物科学实验室进行的。本论文基于发表在国际期刊上的3篇同行评议文章和1篇综述。诊断性或治疗性上尿路内镜手术通常被视为微创手术，并发症发生率较低。最常见的是发热或疼痛，有时会出现败血症。然而，黏膜损伤甚至输尿管破裂也是已知的并发症。研究表明，这些手术过程中产生的高肾盂压力可能导致术中/术后出现并发症，甚至可能造成肾实质损伤。尽管如此，此前尚未尝试通过局部（腔内）给予松弛药物来降低肾盂压力。本论文的目的是研究局部（腔内）给予非特异性β - 肾上腺素能激动剂异丙肾上腺素（ISO）对以下方面的影响：1）猪输尿管的正常压力 - 流量关系；2）软性输尿管肾镜检查期间腔内灌注ISO的效果；3）半硬性输尿管肾镜检查期间的压力 - 流量关系；4）心血管系统。除其他受体类型外，β - 肾上腺素能受体位于上尿路，其激活介导平滑肌松弛。我们在动物实验模型中表明，向冲洗液中添加ISO对上尿路内镜检查期间产生的肾盂压力有显著影响。ISO显著且剂量依赖性地使正常压力 - 流量关系降低约80%，且无伴随的心血管副作用或可测量的血浆ISO水平。在软性输尿管肾镜检查期间，与单独盐水灌注相比，向冲洗液中添加0.1μg/ml ISO可显著降低灌注期间的肾盂压力。ISO灌注期间获得的压力保持在肾内反流的临界压力以下。半硬性输尿管肾镜检查期间的压力 - 流量关系呈线性，ISO可显著降低肾盂压力，但未低于肾内反流的临界水平。总之，在本猪模型中，内镜手术期间向冲洗液中添加0.1μg/ml ISO是安全的。在本论文之外，我们在一项人体试验中证明了向冲洗液中添加0.1μg/ml ISO的松弛效力，并发现其安全。未来应评估该领域在松弛效力、并发症发生率及疼痛发作等方面的进一步研究，尤其是随机临床试验。向冲洗液中添加松弛药物可能在未来对上尿路的治疗性或诊断性内镜手术有利。
