We developed a new resection device-the Rotoresect -with the aim of reducing morbidity during transurethral resection of the prostate (TURP). During rotoresection, a rotating ablator electrode enables simultaneous tissue coagulation by high-frequency current and mechanical tissue ablation. The tissue ablation rate and the extent of bleeding were quantified ex vivo using a blood-perfused porcine kidney (N = 30) and then compared with loop resection and electrovaporization (grooved roller/Rollerball). Additionally, transurethral rotoresection of the prostate and open partial resection of the liver were carried out in five dogs. With the blood-perfused porcine kidney, we demonstrated that the tissue ablation rate increases with increasing of the coagulation current and rotation speed of the ablator electrode. The Rotoresect achieved a tissue ablation rate comparable to that of the resection loop (5.5-6.0 g/min), which was more than twice the rate achieved by electrovaporization (1.7-2.0 g/min). The extent of bleeding during standard loop resection was many times higher (16.5-18.0 g/min) than that induced by rotoresection and electrovaporization (< 2.3 g/min). In our in vivo canine trials, we performed transurethral prostate resection and open segmental liver resection with minimal bleeding. The Rotoresect is a promising instrument for ablation of parenchymal organs during transurethral, laparoscopic, and open surgical procedures.

Using the new electromagnetic shockwave source of the Modulith SL 20 shockwave-induced renal trauma was evaluated by acute and chronic studies in the the canine kidney model. In a further study the electromagnetic shockwave source of the Lithostar Plus Overhead module was tested. Overall, 92 kidneys were exposed to shock waves coupled either by water bath (Modulith lab type) or by water cushion (Modulith prototype, Lithostar Overhead) under ultrasound localization. The generator voltage ranged between 11 and 21 kV, the number of impulses between 25 and 2500. After application of 1500/2500 shocks the extent of the renal lesion depended strictly on the applied generator voltage and was classified into 4 grades: Grade 0, no macroscopic trauma detectable (at 11-12 kV); grade 1, petechial medullary bleeding (at 13 kV); grade 2, cortical hematoma (at 14-16 kV); and grade 3, perirenal hematoma (17-20 kV). Whereas at low and medium energy levels the number of shocks played only a minor role, at maximal generator voltage (20 kV) even 25 impulses induced a grade 2 and 600 shocks a grade 3 lesion, emphasizing the importance of shockwave limitation in the upper energy range. In shockwave-induced renal trauma a vascular lesion was predominant and cellular necrosis was secondary. Coupling with a water cushion resulted in a 15%-20% decrease in the disintegrative and traumatic effect, which was compensated for by increasing the generator voltage by 2 kV. Long-term studies showed complete restitution following grade 1 and 2 trauma, whereas after a grade 3 lesion a small segmental and capsular fibrosis without hyperplasia of the juxtaglomerular apparatus was observed. Based on the characteristic ultrasound pattern found in the first study, the threshold for induction of grade 1 lesion was investigated. With both lithotripters a wide range for induction of a grade 1 lesion (Modulith 234-411, Lithostar Plus 220-740) and also a significant overlapping with grade 0 and 2 lesions was seen at low energy settings (levels 2-4). In contrast, the range of shocks (Modulith 96-150, Lithostar Plus 90-142) and overlapping was minimal when high energy was used (levels 7-9). Finally, the disintegration-trauma coefficient combining the results obtained in a standard stone model with those of the canine kidney model was introduced.

Little is known about the mechanisms and determining factors of shock wave-induced kidney trauma. After classification of the renal lesion in a canine model, we attempted to establish an ex vivo model using the isolated kidney of the pig perfused by Tyrode's solution under physiologic conditions. After shock wave application on the Modulith SL 20, vessel lesions were evaluated by microangiography to determine the size and frequency of dye extravasation in the different areas of the organ. Variation of the focus localization caused different patterns of lesions that characterized the pathway of the shock wave. In particular, constant petechial extravasation in the cortex was observed. The generator voltage correlated with the diameter and the frequency of the lesion area. The number of shock waves primarily affected the incidence of vessel rupture in the regions adjacent to the focal zone. Light microscopy revealed dose-dependent necrosis of tubular cells up to gap-like parenchymal defects. Even after application of the minimal shock wave doses, electron microscopy demonstrated vacuolization of tubular cells in the shock wave focus. Traumatic junctions between capillaries and the tubulur system can explain clinically observed macrohematuria without renal hematomas. With this model, it was possible to evaluate localization and dose dependence of shock wave-induced kidney trauma with high sensitivity and reproducibility. Further advantages of the model were easy availability and the fact that studies on living animals were not necessary. Therefore, standardization and comparison of different lithotripters becomes possible.

LU 302 872 (racemate LU 224 332) is a new glycerinic acid derivative related to the selective ETA receptor antagonist LU 135 252. LU 302 872 exhibits high and balanced affinity to ETA and ETB receptors (Ki 2.2 and 5.8 nmol/L), whereas LU 135 252 is ETA-selective (Ki 1.4 and 184 nmol/L). Two hours after oral treatment of rats with 10 mg/kg of LU 302 872 or of LU 135 252, the big ET-1-induced (20 micrograms/kg i.v.) blood pressure increase is inhibited by 59 +/- 8% or 52 +/- 2% (n = 6-8; p < 0.05 vs. control), whereas bosentan is without effect (-6 +/- 7%; n = 6). In guinea pigs, 10 mg/kg p.o. of LU 302 872 inhibited the big ET-1 (20 micrograms/kg i.v.)-induced bronchospasm (reduction in respiratory volume) by 78 +/- 7% (n = 6; p < 0.05), whereas the ETA antagonist LU 135 252 was ineffective (0.2 +/- 37%; n = 6). Hence, a high oral effectiveness of the new ETA/B antagonist could be demonstrated in two species for both an ETA- or an ETB-mediated response. In human prostate tissue (excised during cystectomy in bladder cancer patients), ET-1 and in most cases, the ETB agonist sarafotoxin 6c (S6c) caused contractions of similar magnitude but more sustained than that of norepinephrine (10(-6) mol/L). A high concentration (10(-5) mol/L) of the ETA antagonist LU 135 252 only moderately attenuated ET contractions. The ETA/B antagonist LU 302 872 or its racemate, LU 224 332, dose-dependently inhibited ET-1-induced contractions. S6C dose-response curves, too, were shifted to the right or suppressed by the combined ETA/B antagonist (10(-6) mol/L LU 224 332). LU 302 872 may be a suitable candidate for testing in benign prostate hyperplasia (BPH).