A 6 Endopyelotomy Associated Ureteral Necrosis : Complete Ureteral Replacement Using Boari Flap

Recent experimental studies showed an important role of endothelium derived relaxing factor for cavernous smooth muscle relaxation. Since nitr ic oxide seems to account for the biological actions of endothelium derived relaxing factor, a study was done to examine a possible role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) i n the treatment of erectile dysfunction. To determine a therapeutically useful dose 0.1, 0.2, 0.5 and 1 mg. S I N 1 were injected intracavernously i n patients w i t h erectile dysfunction. Each dose was given to 2 patients. Then, 63 patients received 1 mg. S I N 1 , including 7 who had prolonged erections to minimal doses of papaverine plus phentolamine and 4 who did not respond w i t h a fu l l erection to other pharmacological agents. Intracavernous injection of S I N 1 induced a dose-dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscles. Of the patients 29 had a fu l l , 21 an almost f u l l and 13 a moderate erection to 1 mg. S I N 1 . There were no systemic or local side effects. I n the patients w i t h prolonged erections to papaverine plus phentolamine the mean duration of a ful l erectile response to S I N 1 was 57 minutes. Compared to the responses to a papaverine (15 mg./ml.) and phentolamine (0.5 mg./ml.) mixture, the erection induced by S I N 1 was superior in 10, comparable i n 47 and inferior i n 6 patients. Our data suggest a possible role for S I N 1 i n the treatment of erectile dysfunction. Possible advantages may be that erection is induced by a mechanism similar to that occurring physiologically, a decreased risk of inducing prolonged erections and low therapy costs. K E Y W O R D S : peni le e r e c t i o n , i m p o t e n c e , n i t r i c oxide Cavernous smooth muscles have a crucial role in penile erection. Relaxation of the arterial and sinusoidal cavernous smooth muscles induces an erection by decreasing peripheral resistance, entrapping blood within the sinusoids and restrict­ ing cavernous outflow.1 In vascular smooth muscle endothelium derived relaxing factor is an important physiological mecha­ nism for relaxation.2 The current view is that nitric oxide or a nitric oxide-containing compound, synthetized from L-arginine, accounts for the biological actions of endothelium derived relaxing factor.3 Recent in vitro studies on rabbit and human penile tissues have shown that nitric oxide or a nitric oxidecontaining compound, probably released from nerves, has a role in the regulation of cavernous smooth muscle tone.4"7 In vivo studies in rabbits further support a role for the L-arginine/ nitric oxide pathway in penile erection.8 These experimental data suggest that in the treatment of erectile dysfunction use of the L-arginine/nitric oxide pathway may be an interesting approach, since i t would resemble the physiological sequence of events in erection. Linsidomine chlor­ hydrate (SIN-1) is the active metabolite of the antianginal drug molsidomine9 (N-ethoxycarbonyl-3-morpholino-sydnonimine) and it is believed to liberate nitric oxide nonenzymatically (nitric oxide donor). Preliminary results showed that SIN-1 produces an erection in patients with erectile dysfunction.1 0 We examined the effects of intracavernous application of SIN-1 in 63 men with erectile dysfunction, and evaluated its possible therapeutic potential in the treatment of erectile dysfunction. A c c e p t e d for p u b l i c a t i o n M a r c h 13, 1992. S u p p o r t e d by grants S t i 9 6 / 2 2 f r o m t h e D e u t s c h e F o r s c h u n g s ­ gemeinschaft a n d the S w e d i s h M e d i c a l R e s e a r c h C o u n c i l ( N o . 6837) . P A T I E N T S A N D M E T H O D S SIN-1 was injected intracavernously in 63 patients from our impotence clinic. Before entering the study the patients under­ went a comprehensive evaluation regarding the etiology of the erectile dysfunction, including case history, physical examina­ tion, sexual case history (by a psychiatrist), blood laboratory studies, pharmaco-Doppler ultrasound, single potential analy­ sis of cavernous electrical activity evaluation11 and pharmaco­ logical testing. 1 2 When indicated by case history or the afore­ mentioned examinations,12 pharmaco-angiography or cavernosometry was done. In case the standardized medication of 15 mg./ml. papaverine and 0.5 mg./ml. phentolamine, with a max­ imal dose of 3 ml., did not induce a full erection (at least 3 intracavernous injections were done), prostaglandin E l (maxi­ mal dose 40 μg.) was applied. In case of incomplete erection to prostaglandin E l a combination of 10 ^g. prostaglandin E l and 5 ßg. calcitonin gene-related peptide13 was tried. All injections were done with the patient in the supine position. Only 1 dose a day was injected. To enhance reproducibility the patients were advised to restrain from psychogenic or reflexogenic stimulation. The erectile response was evaluated by a urologist 10, 20 and 30 minutes after the injection. After the diagnostic evaluation all patients were injected with SIN-1 intracavernously. Before the injection the patients were extensively informed about the study and about possible side effects (prolonged erections, systemic side effects, such as decreased blood pressure with unconsciousness, cavernous f i brosis and infection). After the explanation written consent was obtained from each patient. The study was approved by the Ethics Committee of the University of Hannover (approval No. 532). SIN-1 is officially approved for treatment of coronary spasms