International Journal of Impotence Research (2000) 12, Suppl 5, S1±S12 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir
ORAL PRESENTATIONS
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SEXUAL REHABILITATION: CLINICAL EXPERIENCE WITH WITHDRAWN SILDENAFIL CITRATE (VIAGRA TM) IN SPINAL CORD INJURED PATIENTS. ·- G Raviv, RJ Heruti, A Shaked, H Katz, A Ohry, J Ramon and I Madgar. Department of Urology, the Andrology Unit and the Neuro-Rehabilitation department, Sheba Medical Center, Tel-Hashomer, ISRAEL.
Introduction & Objectives: Sexual dysfunction in spinal cord injured patients (SCIP) inflicts significant emotional and physical stress upon the patients. Recently Viagra. a potent inhibitor of cyclic guanosine monophosphate in the corpus cavemosum, was introduced as a new drug for conservative treatment of sexual dysfunction. The aim of this study was to assess the clinical efficacy of Viagra nl in SCIP. Subjects and Methods: 60 patients were included in the study. The patients underwent a complete evaluation process consisting of medical history, physical examination and blood tests. Rigiscan and EMG and SSEP of BCR were performed in patients with incomplete lesions and in those suspected to be of mixed origin. Each patient entering the stvdy completed the International fndex of Erectile Function questionnaire (IIEF). All patients were given 50mg as astarting dose that \vas increased to 1OOmg based on efficacy and tolerance except for quadriplegic and psychogenic erectile dysfunction patients in whom the starting dose was 25mg. Success was defined as improvement in the ability to have sexual intercourse. and the wish to continue the treatment. Results: The average age was 35.2::!::: 11.7 years (range I 9-58). The average age at injury was :!6.8±10.2 years (range 4-56). 35 patients had upper motor lesion. 13 \Vith quadriplegia. The rest 25 patients had lower motor lesion In Group-! 22 out of 35 patients had reflexogenic erection. In Group-11 10 out of25 did not have erection at all. 49 of the patients were able to maintain erection and penetration. The liEF score in this group increased from 11=5.48 to I 8=6.55 {P Conclusions: Oral VIAGRA T\r is o.n effective. tre:J.tment of erectile dysfunction in SCIP. A higher success rate was seen among patients \vith UlvfN lesions (89%). though patients with Uv£N lesions have demonstrated also a remarkable success Quadriplegics may particularly bene tit from this drug. Our recommend initial titration dose of 50 mg and only :s mg for quodripleg:ic patients. Oral presentations S2 34 EFFECf OF IC35l ON ERECTll.E RESPONSE TO VISUAL EFFICACY AND SAFETY STUDY COMPARING ESCALATING DOSES OF APOMORPHINE SUBLINGUAL (SL) TABLETS TO S MG OR 6 MG OF SEXUAL STIMULATION 1 APOMORPI;IINE SL OR PLACEBO IN THE TREATMENT OF MALE Lycklama a Nijeholt AAB , Slob A Koos, Dohle Gert, Forest ERECTILE DYSFUNCTION (MED) Christopher, Rosen Raymond, Padma-Nathan Harin, Meuleman Eugene Dula, Van Nuys CA, William Keating, Scotland PA, Paul Siami, 1 Eric. Academisch Ziekenhuis Lei den, Leiden NL Evansville, IN, Janet O'Neil and Arunima Shukla, Deerfield IL and the Apomorphine SL Study Group (Presented by Dr. Dula) IC35l is a potent, selective, phosphodiesterase type 5 (PDE5) INTRODUCTION AND OBJECTIVES: Apomorphine is a dopaminergic agent inhibitor. The effect on erectile response of IC35l was assessed having erectogenic properties. AP<\morphine has been formulated in a vehicle for by RigiscanTM penile plethysmography. sublingual (SL) administration that ·has been demonstrated to maintain its Baseline erectile response to placebo and visual sexual erectogenic effects while minimizing the side effects associated with other routes of administration. This Phase Ill study was conducted to determine the efficacy and stimulation (VSS) was recorded by Rigiscan during a single safety of. apomorphine SL in an expanded of males with erectile blind placebo test dose. Eligible patients then entered a double dysfunction. The resultS of ·this study compare two fixed dosing regimens of blind, placebo controlled, single crossover phase. In each apomorphine SL and a voluntary optimization regimen versus placebo. treatment period the patient received placebo or IC351 (100 mg) METHODS: This was a multi-center, double-blind, randomized, placebo controlled, four-group parallel, dose-optimization study. Five hundred and sixty followed by RigiscanTM with VSS. The patient also evaluated nine (569) patients were enrolled into this study. Patients were randomized to one of the quality of the erection on a 5-point scale. four treatment groups (placebo, 6 mg fixed dose, 5 mg fixed dose, or a voluntary Forty-four patients having mild to moderate erectile optimization regimen consisting of 2 mg, 4 mg, 5 mg or 6 mg apomorphine SL). dysfunction completed the study. At the base of the penis, the The number of attempts resulting in an erection firm enough for intercourse was the primary endpoint. increase in duration of erection rigidity compared to RESULTS: The average percentage of attempts resulting in an erection firm baseline was 1.43±6.34 minutes (mean±STD) for placebo and enough for intercourse was statistically significantly higher for each of the three 9.43±12.66 minutes (mean±STD) for IC35l The apomorphine SL treatment groups than for placebo, with mean values of 54.0% for mean increase in the area under the rigidity curve at the base was the dose-optimization group, 53.6% for the 6 mg fixed dose, 54.1% for the 5 mg fixed dose versus 34.5% for the placebo group (all p values were <0.001 ). Results 179.0±558.7 (mean±STD) for placebo and 723.8±830.0 from both patients and partners were similar. Nausea was the most commonly (mean±STD) for IC35l Similar treatment effects reported adverse event (mostly mild to moderate) in this trial by 29.3% of patients were observed at the tip of the penis for all variables). taking apomorphine SL 2, 4, 5 and 6 mg in the dose-optimization group versus 48.3% in the 6 mg fiXed dose, 37.8% in the 5 mg fiXed dose and 2.5% in the Eighty-six percent of patients (38/44) reported improved placebo group, respectively. Only 1.7%, 2.2% and 1.7% of the patients experienced erections on IC35l. The patients' median rating of their severe nausea in the dose-optimization, 6 mg fixed dose and the 5 mg fixed dose erections at baseline and on placebo was 2 (partial erection) group, respectively. Four hundred and forty-four (444) patients completed the compared with a median rating of 4 (rigid but bendable) on study. IC35l (p 56 RESULTS OF A PROSPECTIVE MUL TJCENTER TRIAL ON THE SILDENAFIL vs INTRACA VERNOSAL INJECTION (ICI): EFFICACY EFFICACY AND SAFETY OF INTRACAVERNO US ALPROSTADIL AND PREFERENCE IN PATIENTS FOLLOWING ICI FOR> I YEAR ALF ADEX (EDEx" IVIRIDAL ®) IN PATIENTS FAILING TREATMENT Apostolos Apostolidis, Vasilios Tzortzis. Stamatis Papaharitou, Aleka Portseli, WITH SILDENAFIL (VIAGRA®) Konstantinos Yannakogiorgos and Dimitrios G. Hatzichristou Ridwan Shabsigh, Harin Padma-Nathan, Marc Gittelman, James Department of Urology, School of Medicine and Center for Sexual Dysfunction, McMurray, Joel Kaufman, Irwin Goldstein, (R. Shabsigh, NY Male Aristotle University ofThessaloniki, Greece Reproductive Center, Columbia University, New York, N.Y. 10034) Introduction: Comparative data between ICI and sildenafil are still not available. In INTRODUCTION AND AIM OF THE STUDY: Little is known about an the present srudy we evaluated the efficacy of sildenafil, as well as patients adequate alternative for those patients not responding, being not satisfied or preference. in a group of ED patients treated with ICI for more than a year. having contra-indications to sildenafil (Viagra®). This prospective trial Material and methods: Inclusion criterion was history of ICI for more than a year. investigated the efficacy ofintracavernous alprostadil-alfadex (EDEx"/ Patients with contraindication for sildenafil use were excluded from the present VIRIDAL®)in patients not responding to sildenafil (Viagra.. ). sTudy. The design of the sTudy included two phases: during the first phase, patients METHODS: During a four-week at-home screening phase patients were were asked to attempt sexual intercourse at least two times using sildenafil at a dose advised to use sildenafil starting with a 50mg dose. In case patients did not of 50mg, or lOOmg for non-responders (unable to have sexual intercourse). At phase satisfactorily respond the dose was increased to I OOmg sildenafil. If at the 2. responders were asked to use sildenafil for a month period at the preferred dose. end of the screening phase an liEF score of <4 was recorded for question 3 At the end of the month, patients were asked to choose between ICI and sildenafil. and/or 4, and the patients were not satisfied with the Viagra® treatment, the Results: 144 patients (mean age 58±I2.6 years) were recruited, using ICI for a patients were enrolled into the EDEx"!VIRIDAL®phase. Patients were period of20+10 months. Overall, 110 (76.4%)_1Jatients to sildenafil. titrated and used their individual optimal dose for 6 weeks at-home. Efficacy Alprostadil Alprostadi Tri-mix Tri-mix Tri-mix RESULTS: A total of 99 patients (mean age of screened patients 57.9 :010 fig >IOS20f1 0.05-0.3ml 0.35-0.6ml 0.7-lml years and mean duration of ED 5.3 years) were non-responders to sildenafil n=60 n=30 n=21 n=21 n=l2 according to the protocol. The mean number ofViagra® administrations Sildenafil 50 23 (38.3%) 8 (26.7%) 8 (38.1 o/.ol 1 (48%) 0 during the treatment phase was 4. 9 times. The mean dose per administration S ildenafil I 00 31 (517%) 18 (60%) 9 (42.9%) 10 (47.6%) 2 (16.6% was 85 mg sildenafil. 85 patients had at least one administration of No response 6(10%) 4 (13.3%) 4(19%) 10 (47.6%) 10 (83 3% EDEx"!VIRIDAL® in-office and 66 patients injected EDEx" /VIRIDAL ®at Of the 110 responders to stldenafil, 65 (59.1%) preferred to contmue wtth the oral least once at home (ITT population). Total number of injections was n = drug, 31 (28.2%) went back to ICI, while 14 (12.7%) are using both drugs. 553. Fifty-nine patients (89.4%) reported an improvement in attaining an Preferenc Alprostadil Alprostadil Tri-mix Tri-mix Tri-mix erection (liEF question 3) and 56 patients (84.8%) reported an improvement :SIO !11! >1090!11! 0.05-0.3ml 0.35-0.6ml 0.7-1ml in maintaining an erection (liEF question 4), respectively. Fifty-eight n=54 n=26 n=l7 n=ll n=2 patients (87.9%) reported erections sufficient for sexual intercourse. ICI 13 (24.1%) 7 (26.9%) 5 (294%) 5 (454%) 1(50%) There was one serious adverse event during the treatment with Viagra® i Sildenafil 35 (64.8%) 15 (57 7%) 10 (58.8%) 4 (364%) 1(50%) (prostate cancer) and with EDEx"!VIRIDAL®(bladder carcinoma), I Both 6 (11.1%) 4 (154%) 2(11.8%) 2 (18.2%) 0 respectively. These AEs were not related to the study medications. ( ' onclus1ons: 1) Sddenafil1s htghly effecttve m responders to JCI. 2) Pattents CONCLUSION: The results of this trial indicate that the treatment with following ICI for a long period of time, although responders to sildenafil, will intracavernous alprostadil alfadex is an efficacious and sale alternative in remain in this form of treatment. 3) Some patients will choose to use both treatments patients who are non-responders to sildenafil. alternatively 4)ED patients should be aware of all treatment options available. International Journal of Impotence Research Oral presentations S3 78 Long-Term Users of Intracavernous Alprostadil or; A COMPARISON BETWEEN INVICORP AND CAVER Transurethral Alprostadil - JECT TO ASCERTAIN PATIENT PREFERENCE Their Final Decision if challenged by Sildenam (ViagraR) Wallace Dinsmore, Julian Shah, Jacques Buvat,Francois Guiliano,Chris McMahon.Ted McDermot, Dept of Urology Middlesex. Hospital, UK Hartmut Porst,Urological Office, Hamburg,Germany Introduction & Objectives: lnvicorp, a combination of VIP From April 1998 thru February 1999 more than 820 pts. with and phentolamine is under development for patients with erectile dysfunction were enrolled in an independent, non-sponsored moderate to severe ED and in this study is compared against prospective trial with Sildenafil (ViagraR). Among these pts. with Cavelject the most widely used Internationally approved chronic erectile dysfunction 173 patients were using long-term self injection therapy. Methods: This multi-centre study was designed to first injection therapy with PGE (CaverjectR, VlridalRv) and 41 patients 1 ascertain the correct dose of each therapy for an optimum long-term transurethral Alprostadil-therapy with MUSER. All pts. response, followed by a crossover phase in order to compare underwent a ViagraR-trial at home with 2 tablets each dose (25/ efficacy, tolerability and ease of use after up to 4 doses each 50/1 00) in order to decide afterwards which therapy they further of the test medications, Invi corp in ampoules and auto on prefer. injector, and Caverject in its only presentation. Results: Of the 173 pts. using self-injection therapy 51 % (89) Results: 183 patientsentetcd the study, of whom 128 opted for Viagra, 39% (67) further on for self-injection therapy, 6 produced an erection with both Invicorp and Caverject. Overall response in the comparative phase to the 2 therapies %(II) alternated both methods and 4% (6) used VtagraR and i.e. was similar, but only 85 patients completed partly because PGE1 in combination. patients administered less than 4 Cavcrject injections due to Of the 41 patients with MUSER long-term therapy 93 % (38): side effect or a preference for lnvicorp. Invicorp produced preferred after the exposure to ViagraR the oral drug therapy, 5 % i erections with a total lack of discomfort in 75% of patients (2) further on transurethral therapy and 2 % (I) have had no: compared with only 27% on Cavcrject. Twice as many preference. · reported being very satisfied with the Invicorp auto Conclusion: Despite of the availability of efficacious oral drug injectors compared to Caverject and 79% of patients ranked therapy about 40% of those patients satisfied with self-injection Invicorp as their first choice of treatment. Conclusion: In a population of patients who have similar therapy with Alprostadil are further on keeping to this treatment efficacy responses to both drugs, Invicorp™ has been shown whereas this is true for only 5 %in transurethral therapy. Therefore to be better tolerated, and more comfortable to use. The self-injection therapy will also in the future play an important role Invicorp auto-injector has been sllOv.n to be easier to use and but this seems not the case for transurethral Alprostadil-therapy. was the preferred product in two-thirds of the patients. 910 Comparison of Nocturnal Penile Tumescence Monitoring TITLE and Cavemosal Smooth Muscle Content in Patients with ACCURACY OF RADICAL PELVIC SURGERY ASSESSED BY Erectile Dysfunction TWO-CHANNEL CORPUS CAVERNOSUM ELECTROMYOGRAPHY (CC• Onder Yaman, Erda! YJimaz, Murat Bozlu, Kaan Aydos, EMG) Kadri Anafarta AUTHOR(S) Urology Department, Sthool of Medicine, University of F. Sasso, G. Gentile, E. Alcini, G. Gulino Ankara, Turkey. Objectives: Nocturnal penile tumescence monitoring was INSTITUTION compared· to cavemosal smooth muscle content in 48 cases of Department of Urology, Catholic University, Rome, Italy erectile dysfunction. ABSTRACT Materials and Methods: Pre-operatively nocturnal penile tumescence rigidity (NPTR) testing, colour Doppler sonography Radical cystectomy or prostatectomy generally Implies high rates of erectile failure (25- and if needed pharmaco cavemosometry-cavemosograhpy were 85 %) due to both a neuroger)lc or artertogenlc damage.It was observed that high evaluated in 48 impotent patients before surgical intervention. rates are only related to the Integrity of both neurovascular bundles.Positive The 40 patients whom all those diagnostic tools were abnormal response to slldenafll has been reported in 84% of the patients with erectile dysfunction aftl!r radical bilateral ni!!Ve sparing prostatectomy, whereas high rates of fauures have constituted the first group. In the remaining 8 patients which been desalbed in case of unilateral or non-ne International Journal of Impotence Research Oral presentations S4 11 12 THE ROLE OF AUDIO-VISUAL STIMULATION IN THE AUDIOVISUAL SEXUAL STIMULATION BY VIRTUAL ASSESSMENT OF PATIENTS ADMITIED WITH ERECTILE GLASSES PROMOTES COMPLETE CAVERNOSAL DYSFUNCTION SMOOTH MUSCLE RELAXATION: A DICC STUDY Edoardo S. Pescatori, Vittorio Silingardi, Andrea Ranzi, Gianfranco Hakan 6zveri*, Kamil <;am**, Tufim Tarcan**, Atlf Contalbi, Waher Artibani. Modena University- ITALY *ORO-TIP Saghk Hizmetleri, Istanbul Introduction: Audiovisual sexual stimulation (AVSS) is commonly **Marmara University, School of Medicine, Dept. Of Urology, Istanbul utilzed to promote complete smooth muscle relaxation (CSMR). Our aim was adapt conventional AVSS to particular test conditions, i.e. Audio-visual erotic stimulation (AVES) has been proposed as an initial when the presence of medical personnell is required in the room screening test to rule out psychogenic erectile dysfunction and spare more during testing, and when genitalia can not be directly stimulated. Both invasiVe and expensive tests such as Doppler ultrasound or conditions apply to pharmacocavernosometry/graphy (DICC), and to intracavernosal injection tests. The aim of our study was to assess the role evaluation of female sexual function/dysfunction. of AVES in the evaluation of erectile dysfunction by comparing our Methods: Candidates to DICC have been randomized in two groups AVES findings with color Doppler studies. (no-AVSS and AVSS with virtual glasses). During phase 1 of DICC Fifty patients (mean age: 44, 74±16,43, range: 20-76 yrs.) who admitted we utilized the Virtual i.O Personal Display SystemlM Virtual with erectile dysfunction were evaluated with detailed medical and sexual i.glasses!lM, with tri-dimentional capabilities, stereophonic history and physical examination and determinatioo of serum testosterooe headphones, linked to a VCR playing an erotic movie. Such device and prolactin levels. All patients underwent a 30 minute AVES test with partially excludes the patient from the surrounding enviroment. Rigi-Scan monitoring. The test was repeated if the initial AVES was negative. Finally, all patients were evaluated with penile Duplex BIMIX (papav.lphentol.) 2 ml was intracavernosally administered, ultrasound AVES results were then correlated with the ultrasound and possibly repeated (re-dosing) until CSMR was obtained (3 results. doses/patient maximum). CSMR was defined as linear relation among In the whole group, AVES was found negative in 33 and positive in 17 flows to mantain different intracavemosal pressures, whenever patients. 3 patients with positive AVES have been diagnosed with venous possible, and as occurrence ofthe patient "best quality erection". vascular insufficieny by the Doppler studies. 21 patients out of 33 who Results: No-AVSS group= 18 pts.; AVSS group= 19 pts .. had a negative AVES were found to have vascular erectile insufficiency Required doses: no-AVSS group= 6 pts. needed 1 dose, 3 pts. 2, 9 whereas 12 were found normal by Doppler US. According to these pts. 3 (mean doses: 2.17); AVSS group= 15 pts. needed 1 dose, 1 pt. findings. AVES showed a 87.5% sensitivity and 53.8% specificity rate 2, 3 pts. 3 (mean: 1.37). Significant difference: t-test= 0.007. CSMR, in the diagnosis of vascular erectile dysfunction. 14 patients with regardless number of doses: no-AVSS group= 9 pts. (50%); AVSS positive response to AVES could have been saved from further group= 16 pts. (84.2%). Significant difference: chi-square= 0.026. investigatioo if only AVES had been chosen as an initial screening test. Conclusions: AVSS through virtual glasses significantly promotes A positive result obtained from AVES in an office setting can prevent complete smooth muscle relaxation, therefore reducing the need of re unnecessary further evaluation not only from the cost-effectiveness point dosing during DICC in a significant manner. This strategy is a of view, but also as a minimally invasive test especially for those who promising tool in the evaluation also of female sexual has psychogenic cause of erectile dysfunction. function/dysfunction. 13 14 IS NORMAL HEMODYNAJv!lC RESPONSES !NVARIABL Y WITHDRAWN ASSOCIATED NORMAL PENIL RIGIDITY AND POTENCY? Tibet Erdogru. Murat SaYaj. Nanuk Y1lmaz. Ali Mutlu Atc1 Akdeniz Uni\"ersitY Faculty of Medicine Department ofUrolol!) Antalya. Turke\ lmpotencc due to inadequate penile axial nta! o-:cur ill sonic patients because of unusual tissue mecanical factors of penis and·or its tjssuc properties. despite adequate intracayemosal a11d sufficient hemodynamic integrity. We investigated erectile respon International Journal of Impotence Research Oral presentations S5 15 16 IS DIAGNOSTIC WORK-UP NECESSARY IN ED PATIENTS? WITHDRAWN Konstantinos Hatzimouratidis, Michalis Bekas, Apostolos Apostolidis, Vasilios Tzortzis, Evangelos Ioannidis and Dimitrios G. Hatzichristou Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Greece Introduction: The availability of oral therapy for ED, in conjunction with the media interest for the condition, had as result an increasing number of patients and physicians to express interest for ED treatments. As a consequence, men with ED undergo little or no evaluation before treatment is initiated. The objective of the present study was to identifY the value of work-up for ED pts. Methods: The study included all patients who presented at an ED outpatient clinic. Initial evaluation included medical and sexual history, blood tests, physical examination and intracavemosal injection test (ICI). Patients with negative initial screening were evaluated with specific diagnostic procedures, such as NPTR, Duplex ultrasonography, DICC. All data were introduced in a data base, in order to identifY the importance of its one of the screening steps. Results. 1644 pts were visited the ED clinic, during a 3 years period. 368/1644(22,4%) of them were excluded from the study, due to severe psychiatric (5,2%) or cardiovascular (2. 7%) disease, or history of ED for < 3 months (14,5%). The rest 1276 pts, aged 56± 14 years, had a duration of ED 4,9 ± 3,4 years. Medical history revealed medical conditions associated with ED in 57% of the pts, while blood tests revealed undiagnosed medical conditions in 6.2%. Physical examination in association with ICI revealed the aetiology of ED in 16.5% of the pts. The initial screening was negative in 259(20.3%). In 181 (69.9%) of them, specific diagnostic procedures revealed organic cause of ED, while the rest of them (30.1%) had normal findings and ED was considered as purely psychogenic in origin. Conclusions: ED screening may include medical and sexual history, minimal blood testing, physical examination and ICI. Such screening may diagnose reversible causes of ED, unmasking also medical conditions having ED as first symptom. Such observations are of fundamental significance in the development of guidelines for the diagnosis and treatment of ED. 17 18 ACUTE HYPOXIA INDUCES PDGF-PROTEIN AND PDGF EFFECT OF SILDENAFIL ON NON-ADRENERGIC RECEPTOR EXPRESSION IN SMOOTH MUSCLE CELLS IN RAT NON-CHOLINERGIC NEUROTRANSMISSION IN CORPUS CA VERNOSUM BOVINE PENILE SMALL ARTERIES S. Basciani, P. Visca, M. Arizzi, V. Bonifacio, L Gnessi and A. Fabbri. Chair of Andrology, Dept. of Medical Pathophysiology, University of 1 2 Rome and Cytopathology Service, l.stituto Regina Elena, Rome, Italy. U. Simonsen , J. Contreras', A. Garcia-Sacristan , D. Prieto1.2. 1Department ofPharmacology, University of Aarhus, 8000 Aarhus C, Objectives: It has been recently reported that platelet-derived growth factor Denmark, 2Department of Physiology and 'Department of (PDGF) is expressed in fibroblasts from pathological tunica albuginea of impotent men with Peyronie's disease and VOD. In the present study we Anatomy, Faculty of Veterinary Science, Universidad Complutense e'amined the localization of PDGF A- and B-subunit and of the PDGF 28040 Madrid, Spain. receptor (PDGFR) a.- and J3-subunit in rat isolated corpus cavemosum smooth muscle cells (CC-SMCs) under conditions of generalized acute hypoxia by The purpose of the present study was to investigate whether the immunohystochemistry. furthermore, tissue expression of PDGF and its selective phosphodiesterase isoenzyme V inhibitor, sildenafil, receptors were evaluated by semi-quantitative RT-PCR. • Mattrials and Methods: Twenty adult (60 days) male Sprague-Dawley rats influences the non-adrenergic non-cholinergic neurogenic relaxations were acutely exposed (6 h') to low oxygen tension (02 10'/o, or nonnal ofintracavemous penile small arteries (internal diameter 300-700 J.lm) air (02 20'/o, Therefore, animals were sacrificed, arterial pO, was isolated from young bulls. Endothelium-denuded arteries were determined and tissue specimens were either fixed in Bouin's solution and suspended in an isometric microvascular myograph as earlier paratlin embedded or frozen in liquid nitrogen for immunohystochemistry and RT-PCU. analysis, respectively. CC-SMCs. deparatlinized sections were described (Simonsen eta!., J. Urol. 1997; 157, 2356-2360) in the incubated overnight at 4'C with 1: I 00 dilution of the primary antibodies. The presence of guanethidine (10 J.!M) and atropine (0.1 J.!M), contracted following antisera were used: affinity-purified policlonal rabbit anti-human with 5-hydroxytryptamine (0.5 J.!M), and electrical field stimulation PDGF-AA and anti-PDGF-DB antibodies and monoclonal mouse PDGFR a.• (EFS) was performed. Dense plexes of nerve fibres immunoreactive and antibodies (Genzyme, Cambridge, MA). Control sections were for neural nitric oxide (NO) synthase were observed in the adventitia reacted with the specific antibodies and preincubated overnight with the corresponding antigens media junction of the penile small arteries. The inhibitor of NO synthase, N"-nitro-L-arginine, L-NOARG (30 J.!M), and the selective Results: Hypoxic rats had lower arterial p02 (30±5 mmHg) than control animals (60±4 mmHg; p International Journal of Impotence Research Oral presentations S6 19 20 ACITVATION AND PCllENTIATION OF 1HE NOclJMP PATIIWA Y BY N• ULTRASTRUCTURAL AND ENDOTHELIN-8 RECEPTOR HYDROXY.L-ARGININE IN RABBIT CX>RPUS CAVERJIOSUM UNDFR SITE CHANGES IN THE CAVERNOSA OF A RABBIT NORMOX!CANOINPOXICCONDillONS. MODEL OF BLADDER OUTLET OBSTRUCTION. J:Mer l'a:md,Am.Puigvert,l'vlai!mRaseM, Masood Khan, Faiz Mumtaz, Cecil Thompson, Dimitri &Ilia Gibnh:l,ArgeuimFernhl-z, lnij;p Slimzd:Ttjala. Ftnb:m Mikhailidis, Robert Morgan. Royal Free Hospital, London, UK. Jll!".tlalnw:!ligacmy Mach!, Spain When nitric oxide synthase produces nitric oxide (NO) from N Introduction: Erectile dysfunction (ED) is a common problem hydroxy-L-arginine (OH-arg) instead of L-arginine, the need for affecting the quality of life and psychological well-being. Benign molecular oxygen and NADPH to form NO is reduced. The aim of prostatic hyperplasia (BPH) is the commonest known benign this work was to evaluate the effects of OH-arg on the contractility of proliferative disorder. There is growing evidence to suggest that rabbit corpus cavemosum and to compare the ability of L-arginine and BPH may be associated with ED. OH-arg to enhance the NO-mediated responses In presence of low Endothelin-1 (ET-I) is a potent vasoconstrictor peptide that is oxygen concentrations. In normoxic conditions, OH-arg (I [1M to I thought to play an important role as a modulator of erectile mM) was able to relax precontracted rabbit trabecular smooth muscle. physiology and dysfunction. We investigated whether there are OH-arg-induced relaxations were inhibited by the NOS-inhibitor, L any changes in the penile histology and in the density and NNA (300 f.1M), and by the guanylyl cyclase inhibitor, ODQ (20 flM). Relaxation elicited by OH-arg (300 [!M) in absence of oxygen was distribution of ET-1 and its receptor subtypes in the cavemosa of significantly greater than in normoxic conditions (57.0±4.6% vs a rabbit model of partial bladder outflow obstruction {BOO). 28.0±5.6%; p < 0.05). After treatment of the rabbit corpus cavemosum Materials and methods: BOO was induced in 12 ·New strips with acetylcholine (ACh; 0.3 J.LM), once 11 stable plateau was Zealand White rabbits. Sham operated rabbits acted as controls. reached, addition of OH-arg resulted in further relaxation while Penises were excised after 3 and 6 weeks ( n=6 each for control uddition of L-arginine did not. Administration of OH-arg, but not L• and BOO). Low- and high-resolution autoradiography was arginine, produced a significant increment of cGMP accumulation in performed for ET-1, ETA and ET receptors. Ultrastructural rabbit corpus cavcmosurn tissue (3.58±0.34 vs 2.11± 0.19 pmollmg evaluation of the corpus cavernosum (CC) was also performed. protein; p < 0.005). The increase of cGMP levels induced by ACh (30 Results: ET-1, ETA and ET8 receptor binding sites were j.ll\.1) was significantly enhanced by addition of OH-arg (300 [!M) in primarily localised to the smooth muscle cells (SMC) of the CC normoxic conditions (3.64±0.35 vs 5.24±0.73 pmol/mg protein; p < and the endothelium lining the cavemosal space. ET8 receptor 0.05), as well as in absence of oxygen (1.00±0.09 vs 1.40±0.15 binding sites were significantly decreased (p=0.04) in the 6 week pmol/mg protein; p < 0.05), while L-arginine did not alter the effects BOO CC. There were also ultrastructural changes in the CC. of ACh. Results show that OH-arg is a relaxant agent of trabecular smooth muscle, mainly in hypoxic conditions, through a mechanism Conclusions: ET-1 may play a role in the pathophysiology of dependent of NO-formation and that it is able to enhance the NO ED associated with BPH. This may be partly· due to enhanced mediated responses in that tissue. We propose that the use of OH-arg vasoconstrictor actions and SMC proliferation secondary to a could be of interest in the treatment of erectile dysfunction. reduction in ETn receptors. 21 22 OMRACfERIZATION OF GLYCOSAMINOGLYCANS (GAGs) IN VULVAR VESTIRULITIS SYNlJIWME, VAGINISMLJS AND HUMAN ERECTILE TISSUE I'ELVIC FLOOR DYSFUNCTION 1:'11 NULLIPAROUS WOMEN: Antonis Goulas, Eleni Papakonstantinou, George Karakiulakis, Vasiliki MirL•ou• BEHAVIOURAL APPROACH Fidani and Dimitrios Ilatzichristou. GraztoHin. Ekna CasroltlJ. Stda.10 Salvatore. Department of Phonnacology and Center for Sexual Dysfunction, Aristotle Salonia, Tommaso Maga and Francesco Montorst. Milan, ltaJ,. University ofllJCssaloniki, Greece. Glycosaminoglycans (GAGs) are important constituents of the extracellular BACKGROUND. Vuhar Vestibultt1s Srndrome (VVS) is an matrix, whose role in erectile physiology is largely unknown. l11e purpose of the intlammator\ condttton of the vulvar I'L'stibulc, affecting on I 0 present study was to isolate, identify and characterize tl1e GAGs present in the to 15% of \\Omen att.;nding a clinic. This syndrome is different layers of the human penis. classically charactenzcd by severe pain on vestibular contact or Tissue samples were obtained from 6 potent patients (aged 38-61 years), attempted 1aginal entry, tenderness to pressure within the vulvar who underwent partial pencctomy for localized penile cancer. The samples were 1estibule and physical findings of \'UI\ar erithema of various degrees. dissected into individual layers. Total GAGs were isolated and purified from tunica!, cavemosal and urethral layers following hy tissue mincing, ultrasonication, Surgery ( vcstibulcctomy) is suggestcJ when conservative treatments lipid extraction, extensive digestion wiU1 pronase and DNase, treatment with alkali have failed horohydride and ethanol precipitntion. The etl1anol-precipitated GAGs were AIM of the PRESENTATION. Analysis of 72 consecutive cases of VVS reconstituted in water and fractionated by anion exchange chromatography on DEAE attending our Center ti·om September I, 199X to June I. 1999 showed Scphaccl columns. Measurement of the uronic acid content of the eluted fractions that VVS is usually accompaincd by a contraction of variable inrensi'ty of revealed an elution pattern characterised by three major peaks (G1, G2, G3). The the levator ani. thts characteristic was not reported in the "classic·· naturelofU1e Gl, G2 and GJ glycan fractions obtained from all individual1ayers was of VVS The contraction. that is cquimlcnt of \aginisnius, investigated using GAG-degrading enzymes. The digestion was monitored by may be so tight as tu cause severe myalgia, with mono or bilateral tender electrophoresis on cellular acetate membranes. points. causmg a sec011dary cause of dvspareunia at mid-vaginal le11el. Results: Gl was identified as hyaluronic acid (HA), 02 as heparan sulphate (HS) The diagnostic omission of this critical part of the VVS may explain wll\ and G3 as a mixture ofdemmtan ami chondroitin sulphates (DS/CS). The relative a high number of pts do not respond to conventional medical treatment abundance of each GAG was characteristic of tl1e layer of origin, as was the and arc therefore recommended to undergo surge'}· A behavioural concentration of total GAGs: approach, aiming ar relaxing the pcll 1c tloor, leads to a complete GAG-associated uronic acids rccovef!· in 44 pts (61.1 %), disappearing of the symptoms and signs in Tunica C. cavemosa Urethra 16 (22.2%) but persistent "pain memory": failures in 6 pts (R.3%) and 6 Total GAGs (ltg/mg 0.75±0 12 1.47:Hl.09 1.49±{).15 pts (8.3%) missed at follow-up. Failures are usually present in pts already d!.l: defatted tissue l treated with treatments (vcstibulectonw and/or laser C02 of I lA (%total) 29.05±4.59 27.60±330 35.52±4.02 the \'cstibule) \\hen pennanct organic outcomes ahave alread,· been liS (% totnl) 6.80±0.58 25.79±1.97 14.03±1.11 established. contributing to chronic pch ic pain of peripheral neurologic DS/CS (%total) 64.09±408 46.62±1.61 50.46±1.19 origin. CONCLUSIONS. E1aluation of the pchic lloor tonus (till is Conclusions: ll1e different layers of the nom1al human penis produced a prolile of GAG types consistent with their histological and functional characteristics. ma11datof! in pts sufl\;riug from VVS. Bcha1iouml tretament ma> kad tu Alteration of this prolile in pathological situations, such as Peyronie's disease and re>ulls. at lower cost. \\ith \lrtuall' no a\ oidmg vcno-occlusive dysfunction, can be of profound research and diagnostic interest. aggrt.!'ssiH: and pokntially dangerow:: International Journal of Impotence Research