Endoluminal pharmacologic stimulation of the upper urinary tract.

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.