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Home , Endothelial NOS, Human penis, Nitroarginine

International Journal of Impotence Research (1999) 11, Suppl 1, S65±S72 1 2

DOES CHANGE IN CARDIOVASCLL\R RISK FACTORS SERUM :\ND : PREVENT ERECTILE DYSFUNCTIO'.\? Carol A. Derby, Beth LONGITUDINAL DATA I R0\1 THI \:IASSACHUSETTS A. Mohr, Irwin Goldstein, Henry A. Feldman, Catherine B. MALE AGING STUDY. lknrv A. Idd1nan*, Christopher Johannes, John B. McKinlay (New Engbnd Research Institutes, Longcopet, and John B. I\IcKinlay' 1*Ncw England Research Watertown, MA 02742, USA). Inst., Watertown MA; tliniv ..\1a,s. \frd. Ctr., Worcester MA). Erectile dysfunction (ED) increases in prevalence with age, Although modifiable risk factors for erectile dysfunction (ED) but its relation to the slow decline in serum or other have been identified, little is known regarding prevention. We hormones controlling sexual function is uncertain, despite prospectively examined the association of changes in smoking reports of amelioration hy supplemental testosterone. In the (yes/ no), heavy alcohol use (>3 drinks /day), sedentary lifestyle Massachusetts Male Aging Study, a large population-hascd (< 200 kcal/day of moderate to intense activity) and obesity (BMI random sample of men aged 40-70 were twice interviewed at 2 2: 30 kg/m ) to incident ED in the randomly selected cohort of the home, in 1987-89 and 1995-97, on each occasion providing Massachusetts Male Aging Study. Of 1709 men aged 40-70 in comprehensive health information. blood samples, and a 1987-1989, analyses included 593 with follow-up in 1995-1997 privately completed sexual ,1c1i,itv LJUcstionnaire. We analyzed who were free of ED at baseline, had no history of a subsample of 634 men vv hu had minimal or no ED at baseline cancer, and were not treated for disease or . The and were free of diabetes. pms1at,' sur~rry. heart disease, or relation of risk status to incident ED (1\=102) was examined related . Horm<>nc· lcv ch were divided into low, using multiple logistic regression adjusted for age, hypertension, 111iddle, and high tertiles r, ,r an,dvsi, 1T 1. T2, T3). depression and testosterone. ED was defined by a private, self­ Incident ED (moderate ur C()mplctc I in the interval between administered questionnaire. For each nsk factor a 4-level baseline and followup was I (iA',r ov-er,tll. adjusted for age, and variable was created to represent men who stopped, acquired, or was significantly related to followup testosterone level (21.9% maintained the factor during follow-up, and were never exposed. in Tl, 14.9% in T2, 11.7% in T3) but not to baseline level. Changes in smoking and alcohol were not associated with ED. Incident ED was most frequent (24.4%) in men who showed a Baseline obesity predicted higher risk regardless of follow-up large decline in serum testosterone, from T3 at baseline to Tl at weight loss (p=0.007). Physical activity was associated with ED followup. and least frequent (6.8%) in those who showed a large (p=0.02), with risk highest among men who remained sedentary increase, from Tl to T3 (none receiving supplemental (probability, 95% CI 0.27, 0. 18-0.38), and lowest among those testosterone). Incident ED was frequent in men showing large who remained active or who initiated activity (probability, 95% changes in serum LH, those rising from Tl to T3 (30.2%) or CI 0.14, 0.l l-0.19 and 0.09, 0.04-0.16, respectively). Mid-life falling from T3 to TI (47. l '7, 1. Other honnones (DHEAS, DHT, changes may be too late to reverse the effects of smoking, obesity SHBG, FSH, estrone, cortisol. PR!,) .showed no relation to ED. and alcohol on ED. However, physical activity may reduce risk Our results suggest that al1hnu:;h ED 1, related to concurrent even if initiated in mid-life. Early adoption of healthy behaviors testosterone and LH level.s. hm1111 J11c il'vcls are not useful for may be optimal for prevention. predicting ED in middle-ag,·d men uvn an 8-10-year interval.

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COMPARATIV~. ~:PIDEMIOLOGY OJ<' t:RECTILt: SEXUAL DYSFUNCTION IN WOMEN: OFFICE BASED SURVEY DYSFUNCTION '.ED) IN GAY MEN. Leslie Goldberg. OF WOMEN IN BOTH UROLOGIC AND GYNECOLOGIC Marc F. Stern, Da, id S. Posner, (MFS) Div. General Internal PRACTICES. Wellman W Cheung, Nabet G Kasabian, Stanton C Medicine, Albany Medical College, Albany, NY 12208 Honig, Mary J Minkin, Bruce R Gilbert, 900 Northern Blvd.,Suite Purpose: Discmsion of ED often explicitly or implicitly as­ 230, Great , New York 11021 sumes that a patient's partner is a female. What little we know Introduction: The success of treating male has about ED in the setting of non-traditional relationships such as focused attention on women with similar concerns. However, little between gay men i, based on a few case series of gay men in data exists as to the magnitude of the problem or whether women therapy and yields no epidemiological data. This lack of would seek treatment if effective therapy was available. In this study knowledge and discussion may lead to barriers in diagnosis and we evaluate the prevalence of female sexual dysfunction in patients treatment. presenting for routine urologic or gynecologic care. We therefore undertook the first prospective, community-based Methods: 102 women anonymously completed a standardized study to determine the prevalence and etiology of ED in gay men questionnaire at the time of their scheduled visit to either a Methods: Presence and etiology of ED were determined using Gynecologic (N=76) or Urologic (N=26) office for reasons other the erectile function (modified) and 8-question discriminant then sexual dysfunction. function portions of the International Index of Erectile Function Results: The mean age of respondents was 42.9 ± 11.8 years with a (IIEF) and Florida Sexual History questionnaires, respectively range from 24.7 to 78.5 years old. 73% of respondents described Self-administered questionnaires were distributed in public venues their general medical health as excellent, with 6% reporting in San Francisco alld returned by mail to the investigators hypertension, I% smoke and none had diabetes. 39% of these Results Of I 93U questionnaires distributed, 735 (38°/4,) were women stated that their interest in sex has decreased with age. The returned After ex eluding bisexual and HIV+ men, there were major complaints were with an inability to have with 460 gay and 90 he,,:rosexual men ranging in age from 18 to 83. intercourse (28%) or other stimulation (26%), an inability to have ANCOVA analysis using age as a covariate showed no significant adequate (28%) and pain or spasm with relations difference in the prevalence of ED between homo- and heterosex­ (34%). Other complaints included lack of pleasure ( 15.8%), lack of ual males overall when controlling for age, although the increase genital sensation (9.8%) and inadequate sexual excitement (12.2%). in ED with age is more rapid in gay men. Among men with any Overall 81 % of respondents reported some degree of impairment of ED the prevalence of organic (vs psychogenic) ED was 44% in their sexual function while 55% indicated they would seek treatment gay men vs. 27% in heterosexual men; this was not a significant if effective therapy was available. difference (x'=l .6, ::,=0.2). With regard to a question on sexual Conclusions: This survey demonstrates a very high prevalence of practices, many gay men indicated that they did not always female sexual dysfunction in women seen in routine consultation by engage in penetrati ce sn both Urologists and Gynecologists. In addition, there is great interest Conclusions: Using available reliable and valid instruments, we could not find a difrerence in the prevalence or etiology of ED among women for safe and effective treatment options. Physicians between homo-and heterosexual men. Thus questions about ED with training and experience in dealing with male sexual dysfunction may be an important part of a complete history among both sets are uniquely positioned to effectively evaluate and treat women with of men. However, more research is required to determine if sexual disorders and should consider becoming involved in the instruments design,;d for heterosexual men adequately measure treatment options currently available as well as those under this phenomenon i,1 gay men. investigation. Podium presentations

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FEMALE SEXUAL DYSFUNCTION: PREVALENCE INJECTION OF GLUTAMATE SUBTYPE AND PHYSIOLOGIC CORRELATES Lawrence S. Hakim, AGONISTS IN THE PARAVENTRICULAR Rebecca Wein-Szomstein, Deena Evans, Miami, FL and Ajay NUCLEUS OF THE HYPOTHALAMUS OF MALE Nehra, Rochester, MN. (Presented by Dr. Nehra) RATS CAUSES . Abdel R. Zaharan, Pascal Vachon & Serge Carrier. PURPOSE: To study the epidemiology, prevalence and Research Laboratory, Lady Davis Institute, physiologic correlates of sexual dysfunction in the partners of Montreal. men undergoing office urologic evaluation for ED. METHODS: 150 women anonymously and voluntarily Objectives: The objective of the present study is to completed a 2-page questionnaire including: demographic data, evaluate the effect of different excitatory aminoacids medical and sexual history, and questions regarding sexual (NMDA, AMPA & ACPD) on ICP when injected in the arousal and excitement. Six questions specifically addressing PVN. various vaginal and clitoral complaints, such as lubrication, Methods: 30 Sprague-Dawely rats were anesthetised engorgement, sensation and orgasm were included. and placed in a stereotaxic apparatus after catheterization RESULTS: 84/150 (56%) women (ages: 25-82; mean: 54), of the carotid and CC for pressure monitoring. The were diagnosed with FSD, with various vaginal and clitoral rats were subdivided into three groups (n=lO). 5 animals complaints consistent during the course of the sexual relationship, causing personal distress. Severe FSD (3 or more from each group were injected with glutamate subtype sexual complaints) was more likely to be seen in women who agonists in the PVN using a 0.5 µI Hamilton syringe(dose were: 1) older (often menopausal), 2) cigarette smokers, 3) of 60 ng/µl, vol. 0.3 µI, over 1-2 minutes). 5 animals from post-hysterectomy and 4) hypercholesterolemic, versus those each group were used as controls and were injected in the with mild or moderate (1 or 2 complaints) FSD. nearby vicinity of the PVN instead.All injection sites were Decreased vaginal lubrication was more common in pre­ verified. menopausal women with 3 or more vascular factors, or post­ RESULTS: A significant increase in the ICP was seen menopausal women having any vascular risk factor exposure. following the PVN injections with a mean rise of 40.8 CONCLUSIONS: Female Sexual Dysfunction, like its (P<0.002), 23.6 (P

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CENTRAL EFFECTS-OF ON INTRA­ ERECTILE DYSFUNCTION AND PARKINSON'S CAVERNOUS PRESSURE (ICP) FOLLOWING DISEASE: A MODEL IN THE RAT ELECTRICAL STIMULATION OF THE MPOA Abdel R. Zahran, Neil Simmerman, Pascal Vachon and Yshikazu Sato, Arnold Melman and George J. Christ. Serge Carrier. Lady Davis Institute, Montreal. Departments of Urology and & Biophysics, Albert Einstein College ofMedicine, 1300 Morris Park Avenue, Bronx, Objective: Our objective is to establish an animal model NY 10461. of Parkinson's disease for the study of ED. OBJECTIVES: Nnnc oxide (NO)- cyclic guanosine mono­ Materials and Methods: In a stereotaxic apparatus phosphate ( c-GMP) system in the play a critical role in under general anesthesia (pentobarbitol, 60mg/kg), twelve ensuring penile erection. The presence of a parallel NO-cGMP male Sprague-Dawley rats (250-300g) underwent modulatory system in the CNS has been documented, but its trepanation. 6-0HDA (6.5 µg) was injected into precise contribution to erectile capacity is uncertain. The goal of substancia nigra either unilaterally (UI) or bilaterally (BI). current study was to uulize the PDES inhibitor sildenafil to Control animals (n=5) were sham operated (0.9% evaluate the modulatory role of the CNS NO/cGMP system. saline).After 2 months, apomorphine was injected and the :VlETHODS Sprague-Dawley rats were used. Sildenafil 0.1mg / numbers of spontaneous erections were recorded. 0.05ml NaCl were administrated into the subarachnoid space at Intracavernous pressure (ICP) was evaluated by cavernous the level of the atlanto-occipital membrane. ICP and BP were stimulation. Penile shafts were taken for NADPH measured during electrical stimulation of the medial preoptic area staining. Brains were also taken for quantification of ( MPOA,at 50µA), and unilateral cavernous nerve (CN, at Im.A). (DA), DOPAC and HVA by HPLC. Subsequently, L-NAME 1mg/0.05ml NaCl were administrated by Results: UI rats had a significant decrease (p<0.001) in same fashion and ICP and BP were measured. DA, DOPAC and HY A in the injected hemibrain only. RESlJL TS: lntrathecal administration of sildenafil significantly DA, DOP AC and HY A were decreased in BI rats(p<0.05). increased ICP/BP ratio during MPOA stimulation, but not that Apomorphine-induced erections were either decreased in elicited by CN stimulation (Table 1). Tntrathecal L-NAME 8/12 (p<0.02) or increased in 4/12 (p<0.01) UI and BI rats. reduced only ICP response following ·MPOA stimulation_ ICPs were decreased in UI and Bl rats (p<0.01). NADPH Table!. Ch an,esml CP/BP v al ue after mtrath ec al SI'Id en afil was significantly decreased in UI and BI rats (p<0.01). I pre (n=4) I Sildenafil (n=4) I L-NAME (n=2) I Conclusion: Behavioral and physiological changes in I MPOA 0.44±0.05 I 0.62±0.03• I 0.19±0.1• : penile erections were observed with decreases in brain DA I CN () 68=0.03 I o.67±0.03 I o s2±0 04 I . - .. and metabolites. The 6-0HDA model is a good model for *• S,gnihcantly different from pre-administratwn value by ANOV A the study of ED in Parkinson's. CONCLUSION These results suggested that NO-cGMP system in the CNS m18ht play an important integrative role in modulating penile erections Podium presentations

9 10 S67 INCREASES IN CLITORAL AND VAGINAL BLOOD AND VIP: POTENTIAL FLOW FOLLOWING GENITAL NERVE MEDIATORS OF VAGINAL SMOOTH MUSCLE STIMULATIONS IN THE FEMALE RAT RELAXATION Neil Simmerman, Pascal Vachon, Serge Carrier, and Abdel J. Berman, E. Line, I. Goldstein, A. Traish. Boston R. Zaharan. Lady Davis Institute, McGill University, Montreal, Quebec, Canada HJT-1 E2. Introduction: There is limited information available on the mechanisms modulating vaginal smooth muscle Objectives: To establish an animal model to studv female relaxation. The goal of this study was to determine the sexual function. To identify and confirm the pre~ence of effects ofNO and/VIP on vaginal smooth muscle relaxation. both the eNOS and nNOS subtypes within genital tissues. Materials and Methods: bath preparations of Methods: Ten female Long-Evans rats were. Under general isolated rabbit vaginal strips precontracted with anaesthesia (Somnotol, 60mg/kg) the dorsal clitoral and phenylephrine were exposed to increasing concentrations of pelvic plexus were exposed. A laser Doppler VIP or sildenafil. Separately, other vaginal strips were flowmeter was used to measure and record the clitoral and vaginal blood flow. Electrostimulation was performed with treated with bretylium and atropine to isolate NANC a stainless-steel bipolar hook electrode. Then tissues were responses and subjected to electrical field stimulation in the harvest for immunohistology (eNOS, nNOS). absence or presence of the PDE 5 inhibitor sildenafil or the Results: An increase in blood flow of the was seen NO synthase inhibitor L- . following stimulation of the dorsal clitoral nerve (from 9.44 Results: VIP and sildenafil relaxed vaginal smooth muscle ± 3.6 to 16.35 ± 5.8 ml/min/!00g, p<0.001). An increase in in a dose-dependent manner (EC50 = 44 nM and 2. 7 µ},11, vaginal blood flow was also recorded following plexus nerve respectively). Vaginal tissue subjected to EFS exhibited stimulations ( from 6.3 ± 4.7 to 25.8 ± 9.5ml/min/100g frequency-dependent relaxation and sildenafil increased tissue, p<0.001). Both eNOS and nNOS were found to be response amplitude by 20-50% at 0.5-5Hz without affecting present in the clitoral, and proximal vaginal tissues, and were the duration. L-nitroarginine attenuated EFS-induced absent from the distal vaginal tissue. relaxation by 25%. Conclusion: The female Long-Evans rat is a good model for Conclusions: The partial inhibition ofEFS-induced the study of female sexual function. Our results also indicate relaxation by L-Nitroarginine suggests that NO is involved , that NOS is present and may play a role in smooth muscle but is not the exclusive mediator ofNANC relaxation in the relaxation in female genital tract. . VIP may also play an important role in the vagina, as indicated by its high potency. These results suggest that VIP and NO together may contribute to NANC mediated relaxation of vaginal smooth muscle.

11 12 INTRA CA VERNOSAL PRESSURE MONITORING CONFIRMS -TRANSFER OF ENDOTHELIAL NITRIC OXIDE NITRIC OXIDE-DEPENDENT ERECTIONS S~THASE TO THE PENIS AUGMENTS ERECTILE IN -DEFICIENT MICE RESPONSES IN THE AGED RAT Sena F. Sezen, Julie K. Crone and Arthur L. Burnett. Department of Trinity J. Bivalacqua, Hunter C. Champion, Louis J. Ignarro, Urology, The Johns Hopkins Hospital, Baltimore, MD. Philip J. Kadowitz and Wayne J.G. Hellstrom. Tulane University School of Medicine, New Orleans, Louisiana. Objective: We have recently developed a technique to measure the intracavernosal pressure (ICP) as a quantitative assessment of erectile Nitric oxide (NO), a vasodilator involved in penile erection, is response in mice that allows the use of genetically engineered mice for synthesized by the nitric oxide synthase (NOS) family of this research purpose. Thus, the aim of this study was to monitor the . It has been show11 that NOS activity decreases with ICP changes induced by cavernous nerve (CN) electrical stimulation in age as well as erectile responses to cavemosal nerve stimulation. mice with targeted deletions of nitric oxide synthase (NOS) isoforms. In order to determine whether adenoviral-mediated Methods: Adult male neuronal NOS-a deficient (nNOS-/-) mice and endothelial NOS deficient (eNOS-/-) mice (28-36 g) were anesthetized overexpression of endothelial NOS could enhance erectile with pentobarbital (40 mg/kg). Via a midline incision, bladder and responses in aged rats, we administered a recombinant prostate were exposed and bilateral CNs were isolated. A 24-gauge adenovirus containing the endothelial NOS gene angiocath was inserted into the right corpus cavernosum and a 28-1/2 - (AdCMVeNOS) into the corpora cavemosum of the aged rat. gauge needle was inserted into the left corpus cavemosum for ICP Adenoviral expression of the b-galactosidase reporter gene was monitoring and for drug administration, respectively. CN electrical observed in cavernosal tissue one day after intracavemosal stimulation was performed with a stainless-steel bipolar electrode administration of AdCMVbgal. One dav after administration of attached to a Grass-S48 stimulator using the following stimulation AdCMVeNOS, transgene expression w;s confirmed by Western parameters: 16 Hz, 5 ms, 0.5 to 4 V. Blot staining of eNOS protein and cGMP levels were increased Results: In both nNOS-/- and eNOS-/- mice, direct electrical stimulation of CN significantly increased baseline ICP (nNOS-/-: 8.28 in the corpus cavernosum tissue. The increase in cavemosal ± 1.2 vs 31.30 ± 4.7 mmHg, n=4; eNOS-/-: 13.13 ± 2.4 vs 39.69 ± 0.6 pressure in response to cavemosal nerve stimulation was mmHg, n= 5, p<0.05). Pretreatment with L-nitro-arginine methylester, a enhanced in aged rats transfected with eNOS and erectile non-selective inhibitor of NOS, prevented the CN stimulation induced responses to and zaprinast were enhanced one day increase in ICP (nNOS -/-: 19.33 ± 9.7 mmHg, p=0.239; eNOS-/-: 12.6 after transfection. These data suggest that in vivo gene-transfer ± 4.1 mmHg, p=0.913). of eNOS can selectively enhance erectile responses to Conclusion: We have applied ICP monitoring to quantitate erectile acetylcholine and zaprinast. Moreover, these data suggest that responses in NOS-deficient mice. These results support the roles of gene-transfer of eNOS, alone or in combination with a type V alternative NOS isoforms that preserve erectile function in mice lacking phosphodiesterase inhibitor may constitute a new therapeutic nNOS-a or eNOS isoforms. (Supported by NIH-NIDDK I KOS DK02568). intervention for the treatment of erectile dysfunction. Podium presentations

S68 13 14 VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN THE ADULT RAT AND HUMAN PENIS. INTRACA VERNOSAL VASCULAR ENDOTHELIAL Martin Burchard!, Tatjana Burchard!, Min-Wei Chen, Ahmad GROWTH FACTOR PROTECTS ENDOTHELIAL Shabsigh, Alexandre de la Taille, Ralph Buttyan, Ridwan Shabsigh. DEPENDENT CORPORAL SMOOTH MUSCLE Dep_a~ment of Urology, Columbia University, 11th Floor, Atchley RELAXATION: A PRELIMINARY STUDY Pav1hon, 161 Fort Washington Avenue, New York, NY. Gerard D-. Henry, Robert R. Byrne, TTT Huynh, Brian H. INTRODUCTION: Erectile dysfunction is often associated with Annex, Per-Otto Hagen, and Craig F. Donatucci (Duke v_asc_ular insufficiency of the erectile tissue. VEGF is a peptides with University Medical Center, Durham NC) significant vasculogenic activity in vitro and in vivo. It is known from other or~a~s t?at several different mature VEGF mRNA transcripts Atherosclerosis is a major risk factor in erectile dysfunction, exist, ongmatmg from alternative splicing of the primary VEGF and loss of -dependent is an early transcript. These variant transcripts can encode peptides with pathogenic event. We investigated whether VEGF could be different biological activities. This study characterizes the expression used to protect endothelial dependent cavernosal relaxation of the splice variants of VEGF in the rat and human penis. from atherosclerotic injury induced by a hypercholesterolemic METHODS: Penile tissue was obtained from adult rats and from human patients undergoing penile prosthesis implantation. Analysis diet. Isometric tension studies were performed on 2 isolated of various VEGF transcripts was performed using a reverse strips of corpora cavernosa taken from each New Zealand White transcriptase-polymerase chain reaction (RT-PCR) technique with adult male rabbit fed: 1) 4 wk 1% cholesterol diet receiving primer pairs derived from the first and eighth exons of the VEGF weekly penile injections of 0:3 mg VEGF (N=4), 2) 4 wk I% gene. The expression levels of the various isoforms in the rat penis cholesterol diet receiving weekly penile injections of normal were then quantified using RNase Protection Assays. saline (n=4), 3) 4 wk normal diet and injections of VEGF (N=3) RESULTS: Four previously described splice variants of VEGF and 4) 4 wk normal diet and injections of NS (N=3). There was mRNA (VEGF 120,144,164,188) were detected in rat and human a significant elevation in serum total cholesterol (727 ± 75.6 penile tissues. In contrast to rat where the most abundant form of mg.Id!. vs 38.7 ± 5.53 mg.Id!.) p < 0.01. The Cho!NEGF VEGF mRNA is the 188 splice isofonn, VEGF is the most 164 rabbits had higher % maximal relaxation to acetylcholine than abundant _transcript detected in the rat penis. A similar finding was Chol/NS rabbits (94.5 ± 8.41 vs 71.1 ± 8.24) p=0.033. There observed m the human penis. Finally, sequence analysis of numerous was a significant difference in the sensitivity to sodium VEGF cDNA clones obtained from the rat penis demonstrated the presence of a previously undescribed VEGF splice variant that could nitroprusside at ED25 for CholNEGF rabbits compared to give rise to a protein of 110 . Chol/NS rabbits (-7.045 ± 0. 16 vs -6.65 ± 0.14) p = 0.043, CONCLUSIONS: A number of VEGF mRNA isoforms are which was overcome by higher doses of SNP. Intracavernosal expressed in the rat and human penis with the splice variant encoding injections of VEGF appear to protect the endothelium from a 164 amino acid protein present in greatest abundance. This study is hypercholesterolemia induced injury. a prelude for attempts to genetically manipulate VEGF expression in the penis as a gene therapy for vasculogenic erectile dysfunction.

15 16 INTRACA VERNOSAL VASCULAR ENDOTHELIAL INTRA VENOUS VASCULAR ENDOTHELIAL GROWTH GROWTH FACTOR RESTORES CORPORAL SMOOTH FACTOR RESTORES BOTH ENDOTHELIAL DEPENDENT MUSCLE RESPONSE TO NITRIC OXIDE AND INDEPENDENT CORPORAL SMOOTH MUSCLE RELAXATION . Robert R. Byrne. Gerard D. Henry, TTT Huynh; Anne M. Pippen, Brian H. Annex, Per-Otto Hagen, Craig F. Donatucci Robert R. Byrne, Gerard D. Henry, TTT Huynh, Anne M. Pippen, Brian H. Annex, Per-Otto Hagen, Craig F. Donatucci (Duke University Medical Center, Durham NC) (Duke University Medical Center, Durham NC) Penile erection is a vascular event. Therapeutic use of growth The route of administration can affect the efficacy of treatments factors to induce neovascularity has been successfully for erectile dysfunction, as is seen in the difference between demonstrated in models of organ . Our objective was intrauretheral and intercavemosal alprostadil. Our objective was to determine if Vascular Endothelial Growth Factor (VEGF) to determine the effects of intravenously delivered VEGF on could reverse the smooth muscle dysfunction in the both endothelial-dependent and endothelial-independent hypercholesterolemic rabbit model of erectile dysfunction. corporal smooth muscle relaxation in 12 New Zealand White Twenty-four New Zealand White rabbits were fed a 1% rabbits fed a I% cholesterol diet, who received a single cholesterol diet or a normal diet, and received a single intravenous bolus of either VEGF (0.9mg) or VEGF-vehicle intracavernosal injection of either VEGF (0.9mg) or VEGF­ after 6 weeks. ]ell_ day_s_after injection isometric tension studies vehicle at 6 weeks. Ten days after injection, their corpora were performed on corporal tissue. Sensitivity and maximal cavernosa were ·harvested, and isometric tension studies were relaxation to acetylcholine (ACH) and performed. Relaxation to acetylcholine (ACH) and sodium (SNP) were compared between treatment groups. Sections of nitroprusside (SNP) was compared within each group. Sections the corpora were assessed for smooth muscle content and for of the corpora were assessed for smooth muscle content with VEGF protein expression using immunohistochernistry. IV Masson Trichrome staining and for VEGF expression using VEGF treatment significantly augmented endothelium immunohistochemistry. Endothelium-dependent (ACH) and dependent (ACH-mediated) and endothelium independent endothelium-independent (SNP) smooth muscle relaxation were (SNP-mediated) maximal corporal smooth muscle relaxation both impaired in the cholesterol-fed animals (P=0.021, (P=0.014, P=0.018). Moreover, the sensitivity (ED50) to both P=0.003). VEGF treatment restored the nitric oxide-mediated, ACH and SNP was enhanced in the VEGF treated animals direct smooth muscle relaxation to normal levels (P=0.015). (P=0.004, P=0.001). VEGF protein immunoexpression was Decre;ised smooth muscle content was found in cholesterol-fed augmented after VEGF therapy (P=0.05). IV VEGF appears to animals versus normal diet controls (P=0.008), and this was not restore both endothelial-dependent and endothelial-independent affected by VEGF treatment (P=0.450). VEGF expression was corporal smooth muscle functions. augmented after VEGF therapy (P<0.001). Podium presentations

17 18 S69 "FURTHER PROOF OF eNOS AND iNOS IN HUMAN CORPUS DECREASED ERECTILE RESPONSE AND INCREASED CAVERNOSUM" iNOS EXPRESSION IN A RU MODEL OF PEYRONIE'S Allen D. Seftel, Tracy Loye, Chung Ho-Chang Department of Urology and Medicine, Case Western Reserve DISEASE Trinity J. Bivalacqua, Hunter C. Champion, Yogesh Virani, Suresh University, Cleveland, Ohio. C. Sikka, Philip J. Kadowitz and Wayne J.G. Hellstrom. Tulane We have previously demonstrated the presence of eNOS and iNOS University Medical School, New Orleans, LA. via Western blot and immunohistochemistry in human corpus The animal model proposed by El-Sakka et al has shown that cavernosum tissue. Eighteen human cavernosal tissues procured at transforming growth factor-[3 injected into the rat surgery from impotent men, men with Peyronie's disease and men with causes tissue fibrosis after 6 wks (similar to human Peyronie's no disease were now subjected to Western blot for iNOS and eNOS. disease). Men with Peyronie' s disease often suffer from erectile Further, four human corpus cavernosal primary cell cultures were dysfunction (ED). Our aim was to assess erectile function in evaluated to determine the presence of iNOS and eNOS and to examine Peyronie's rats after 6 wks, measure cGMP levels in the cavemosal the effects of acute hyperglycemia on NOS expression. Cells were tissue, and determine the constitutive and inducible NOS maintained in DMEM with 10% FBS and grown in four different activity by L- to L- conversion in the corpus glucose concentrations: 5mM, 15mM, 30mM, and 60mM, for one week. cavernosum extracts. Two groups of CD rats were used: I) saline Total RNA was isolated from these cells at passage 3, utilizing the acid injected (0.1 ml) into the tunica albuginea, and 2) TGF-[3 (0.5 µg) guanidium/phenol/chloroform method. Quantitation of total RNA was injected into the tunica albuginea. Both groups underwent electrical performed by spectrophotometric determination at 260/280mn. stimulation of the cavernosal nerve and phan:nacological Approximately 2 micrograms of total RNA were reverse transcribed into stimulation with acetylcholine, an endothelium-dependent cDNAs with MML V reverse trancriptase and amplified with PCR vasodilator, after 6 wks to assess erectile function. Rat utilizing the iNOS primers. PCR products were separated in a .9% were homogenized with cGMP levels and constitutive NOS enzyme agarose gel and photographs were taken. activity recorded. Erectile function as measured by cavernosal Western blot analysis confirmed eNOS and iNOS expression in human nerve stimulation and acetylcholine injection was significantly cavernosum, with upregulation in diabetic men. While there was a trend lower in the TGF-[3 injected rats after 6 wks when compared to the towards an increase in iNOS mRNA expression with increasing glucose saline-injected rats. iNOS was upregulated and nNOS/eNOS was concentration, there also were age-related changes independent of downregulated in the corpus cavernosum of the TGF-[3 injected hyperglycemia. Cells from a 39 year-old , but not a 75 year-old penises. We have shown that erectile function is significantly man, showed downregulation ofiNOS at 30mM glucose. This data lower in the TGF-[3 injected rats after 6 wks at a time when iNOS is continues to support the presence of eNOS and iNOS in the penile upregulated and either eNOS/nNOS is downregulated in these cavernosum, specifically, cavernosal smooth muscle cells. Also, we animals. These data document a possible mechanism by which have found that iNOS and eNOS are overexpressed in hyperglycemia. men with Peyronie's disease suffer from ED. The quantity ofiNOS mRNA increases with increasing glucose concentration.

19 20 INHIBITION OF NEUROGENIC CONTRACTION BY EVALUATION OF VASOCONGESTIVE ASPECTS SYMPATHOMIMETICS: POTENTIAL MECHANISM OF OF THE FEL\'IALE SEXUAL RESPONSE USING COCAINE AND EPHEDRINE-INDUCED . DUPLEX DOPPLER ULTRASOUND Ricardo M. Munarriz, Erika Line, Irwin Goldstein, Ab

S70 21 22 RESOLLTJON OF SECONDARY PRE:VIATURE EJACCLATION IN IMPOTENT MEN BY SUCCESSFUL ASSESSMENT OF VIAGRA EFFICACY USING A NEW INSTRUMENT ERECTILE DYSFUNCTION INVENTORY TREATMENT OF THEIR ERECTILE DYSFUNCTION. OF TREATMENT SATISFACTION-(EDITS) M:uiiyn Parker, Jolm P Mulhall. Mavwood. IL. USA Patricia Gilhooly, Hong Lim, Karen Long, and Hossein Sadeghi-Nejad, East Orange, NJ Introduction: Erectile dy;fimction (ED) is associated with a INTRODUCTION AND OBJECTIVES: EDITS [Althof, S, et al) is number of sequelae including secondary premature a new, brief, psychometrically sound measure used to assess satisfaction (PE). Tlus latter phenomenon is believed to result from selt: with medical treatment modalities for ED. This validated instrument conditioning in response to a true or perceived reduction in the consists of 15 items and was chosen to evaluate the efficacy of Viagra in ability to maintain erectile rigidity and vaginal penetration. This a selected, previously studied group of men with ED. srudy was undertaken to ascertain if correcting the erectile ME1HODS: The study population consisted of 49 men with multi­ factorial organic ED who completed a randomized comparative impairment helped ameliorate the secondary PE without had ( cross --{)ver) study of MUSE vs. Caverject. 3 5 patients satisfied the concomitant use of any other pharrnacologic manipulation. inclusion criteria. Patients were given 50mg tablets of VIAGRA (x6) Patients and Methods: T11e srudy group comprised men with and instructed to take one tablet one hour prior to intercourse. When ED who also complained of PE whose onset post-dated their ED this dose was found to be ineffective , they were instructed to T11e patients were counseled regarding transurethral and take 2 pills (100 mg) one hour prior to their next anticipated sexual intracavemosal therapies. The patients were interv1e,ved no intercourse. Efficacy was assessed on follow-up visits and validated sooner than 6 months after commencing successful ED therapv to questionnaires including the IIEF and EDITS after an effective dose or 100mg Viagra was tried. EDITS score was determined by the sum of define if their secondary PE had resolved the 15 questrons (04 scale). Results: 38 patients were evaluated. The mean age and duration RESULTS: 27 patients (mean age 62 ± 9) completed the study. of ED were 48±16 years and 22±16 months. The mean duration Compared to no treatment at all, 21/27 patients (78%} reported erection of the PE was l 2±6months and the mean duration of ED prior to improvement and 20/27 (74%) reported improv~ ability to have sexual the onset of secondary PE was 6±3 months. The mean ejaculato0 intercourse with Viagra (50 or 100mg). Of the 5 MUSE and Caverject latency pre-ED was 8±3 mins compared to a latency of 2± I mins non-responders 2 (40%) reported success with Viagra. Mean EDITS at the tinle of presentation. 34/38 (89%) patients responded to score (n=25) was 65. !(range 13.3 - 98.3 ± SD 26.0). Scores of patients vasoactive therapy. 72% of patients had significant improvement choosing Viagra (n=l7) averaged 81.2 (range 65.0-98.3 SD 9.0), those with the lowest 2 scores (average 67.5) were the non-responders to both in their ejaculatory latency and did not require SSRI therapy. T11e MUSE and Caverject. Scores of patrents not choosing Viagra (n=8) inlprovement in ejaculatory latency was seen at a mean of 4±3 averaged 32.5 (range 13.3-61.67 SD 20.0). months after the commencement of therapy. The mean latency at CONCLUSIONS: Efficacy and patient satisfaction with Viagra was this follow-up time was 5±2 mins. high. From this preliminary study, a cutting score of 70 on EDITS Conclusions: These data indicate that men with PE secondary sefected those patients whose satisfaction with Viagra was great enough to ED may benefit from correction of the ED alone which may to make it their final choice. Durability of this finding requires long circumvent the need for SSRl tenn follow up.

23 24 SILDE:"-IAFIL CITRATE IN THE TRA:-.JSPLANT \ L\CiR:\ FOLLOWl:"-IG PROST ATECTOMY RFCIPIFNT WITII ERECTIIF DYSFUNCTION. Gcnthn· \lilwn f\1 Lakin. Sumi ta. Kedia. Frie A. Klein. and Craig D. Zippe. N. Sklar. Corresponding i\ddress: University oPvlaryland Cleveland Clrnic Foundation, Cleveland. Ohio. Medical Systems, 22 S. Greene St. 8SD I 8, Haiti more, Ml) 21201 Purpose: To determine whelher the response to sildenafil citrate (Viagrn1 in patients with erectile dysfunction following radical Introduction: Erectile dysfunction occurs frequently in the prostatcctomy (RP) was influenced by 1) the presence or absence of transplant recipient population as most of these patients have neurovascular bundles, 2) the time interval from surgery to the multiple predisposing factors. These patients can pose a initiation of drug therapy. therapeutic dilemma, as there no major studies on the use of :\Iethods: 90 patients presenting with erectile dysfunction Sildenafil in this group. There are further concerns as both following RP were prescribed sildenafil at a dose of 50mg, with a Cyclosporin A (CSA) and Sildenafil Citrate share a common titration to 100mg if needed. The patients were stratified according with clearance via the CYP3A4 enzymatic to the type of procedure: bilateral NS, unilateral NS and non-NS. All pathway. NS procedures were done by l\vo experienced surgeons. Patients Methods: Since June 1998, 57 organ transplant recipients (40 were interviewed and the International Index of Erectile Function solitary , 8 dual kidney and 9 simultaneous ­ ( IIEF) questionnaire was used. Responses to the IIEF questionnaire kidncy) have been treated for erectile dysfunction using oral (questions 3, 4, and 7) ,vere rated on a scale of 1 (almost never) to 5 Sildenafil. All patients were> 6 months post-transplantation (almost always). A positive response to sildenafil was defined as and were on a steady dosage of CSA. Erectile function was erectlon sufficient for vaginal penetration. assessed using the Sexual Health Inventory for Men as well as a Results: The patients who had bilateral NS, 73% (38/52) global assessment questionnaire. These patients had CSA responded; in those with unilateral NS, 50% (6/12) responded; in levels measured bi-weekly for the 1st 3 months of therapy. those with non NS, 15.4% (4/26) responded. The IIEF showed Results: 35 of the 57(62%) patients were satisfied with their significant improvements in response to questions (ability to sexual function on Sildenafil Therapy. Of these patients 3 adverse events occurred in 4 patients (7%) and one patient penetrate), question 4 (ability to maintain), and question 7 withdrew from therapy as a result. There were no patients ( satisfaction with intercourse) and was higher in the bilateral NS requiring dosing changes in CSA as a result of Sildenafil group vs. the unilateral and non-NS group (P<0.05). No difference therapy. The average number of pills used per month was 3 in in the response rate was noted when the time intervals from surgery this population. to drug therapy was stratified. Conclusions: Sildenafil Citrate is safe and effective in the Conclusions: Successful treatment of erectile dysfunction with transplant recipient population. There is no significant change sildenafil citrate after RP depends on the presence of the in CSA levels in these patients possibly due to the infrequent neurovascular bundles and response does not appear to relate to use of the drug. length of time after surgery. Podium presentations

25 26 S71 OF ORAL PHEN­ UPDATE OF SAFETY AND EFFICACY DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF WITH ERECTILE TOLAMINE (V ASOMAX) IN PATIENTS TOPIGLANTM, A TOPICAL GEL FORMULATION OF 1% and the Vasomax Study DYSFUNCTION (ED). Irwin Goldstein ALP ROST ADIL, FOR THE IN OFFICE TREATMENT OF Group, Boston, MA. ERECTILE DYSFUNCTION. Irwin Goldstein, Terry Payton and Paul J. Schechter, Boston, MA. Introduction: Published data concerning efficacy and safety of is limited. oral phentolamine (Vasomax) in the treatment of ED INTRODUCTION: Efficacy and safety ofTopiglan™ or placebo Methods: Updated data will be presented from a placebo-con­ gel applied to the were assessed in 60 patients with . dose study trolled, parallel group, randomized, double-blind fixed moderate to severe erectile dysfunction in a two visit office settmg. study. Efficacy was and a large, ongoing, open label self-titration METHODS: During the 1st visit open label placebo gel only was of Erectile Function (IIEF) and assessed by the International Index applied; at the 2nd visit blinded random allocation to Topiglan™ the Global Assessment the Sexual Encounter Profile, plus (n=31) or placebo gel (n=29) occurred. An erotic movie showing study, safety by monitoring. Question (GAQ) for the open label heterosexual sex began 30 minutes post-application; a penile vibra­ blind study, compared to place­ Results: In the 424 patient double tor used at 45 minutes. Audiovisual and tactile stimulation were significantly (p<0.5) im­ bo both 40 and 80 mg phentolamine discontinued at 65 minutes, the patient observed until 90 minutes. i~ er~c~ile proved from baseline to end-of-treatment: mean change Erection response was assessed at various times by the investiga­ of penetration and mamtammg function domain scores, frequency tor and patients, signs and symptoms of tolerance evaluated. seve~ty of erection, erectile function domain score, categorical RESULTS: Topiglan™ produced a greater angle of erection (p= with ED, vaginal penetration in 75% of attempts, satisfaction 0.033) and maximum rigidity (p=0.033) compared to placebo gel. study medication, orgasmic function, intercourse, overall_ Responses were greater to Topiglan™ than placebo gel at all time 51% and 53% of patients satisfaction. At 40 and 80 mg doses, points post-application with greatest differences observed at 45 on 75% of attempts. In were able to achieve vaginal penetration and 60 minutes. Twelve of 31 patients (38.9%) on Topiglan™ and open label study, 73% reported improved erectile the 2003 patient only 2 of29 (6.9%) on placebo gel achieved an erection judged the GAQ after 2 months function scores on the IIEF, 69% on sufficient for vaginal penetration (p=0.005). Penile erythema was combined studies (n= 2923) treatment. Adverse events (AEs) from more common with Topiglan™ while symptoms of minor to mild rhinitis (16.5, for 40 and 80 mg phentolamine vs. placebo included warmth or burning and, less commonly, tingling and coolness 14.8, 3.8%), headache (4.9, 3.0, 1.7%), dizziness (2.6, 4.6, 0.2%) were reported by most patients following both Topiglan™ and . and tachycardia (1.8, 3.3, 0.6%). Among patients with placebo gel. No significant changes in vital signs were noted. cardiovascular disease (CAD, MI, CV A) AEs on phentolamme vs. CONCLUSIONS: A beneficial effect ofTopiglan™ applied to the . placebo were similar (18.3% vs 20.8%). . glans penis to increase penile rigidity and expectations of vaginal phentolamine is a safe and effective first !me Conclusion: Oral penetration in men with erectile dysfunction was demonstrated. therapy for erectile dysfunction.

27 28 GR.\.FTS DURING RADICAL PROSPECTIVE MULTICENTER TRIAL ON THE EFFICACY BILATERAL NERVE RETROPUBIC : A ONE YEAR AND SAFETY OF INTRACAVERNOUS ALPROSTADIL­ FOLLOW-UP. Edward D. Kim. Dov Kadmon, Brian J. Miles. FAILING ALFADEX (EDEX®MRIDAL®) IN PATIENTS Larry I. Lipshultz, Peter T. Scardino. Kevin M. Slawin. Vicky SILDENAFIL (VIAGRA®). Ridwan Shabsigh, Harin Padma­ Tang, Thomas M. \vl1eelt:r. and Rahul Nath. Address corres­ Nathan, Marc Gittleman, James McMurray, Joel Kaufman and pondence to Edward D. Kim. M.D .. 6560 Fannin, Suite 2100, Irwin Goldstein (presented by Dr. Shabsigh) Houston. Texas 77030. Introduction/aims: This prospective trial investigated the efficacy of intracavernous alprostadil-alfadex (EDEXMRIDAL) Purpose: We have previously presented the technique and in patients not responding to sildenafil (Viagra®). return of erectile function in a patient using interposition sural Methods: During a 4-week at-home screening phase, patients nerve grafting in place of the resected cavernous nerves at the used sildenafil escalating up to 100 mg as needed. If at the end of time of radical retropubic prostatectomy (RRP) (Kim ED, et al: the screening phase an IIEF score of <4 was recorded for question J Urol 161:188-192, 1999). The purpose of this study is to the efficacy of this procedure in a larger series of 3 and/or 4, & the patients were not satisfied with Viagra®, they determine men with at least 1 year follow-up. into the EDEX®NIRIDAL® phase. After titration were enrolled Methods: Potent men (mean age 57 ± 6 years) with clini­ at-home. to their optimal dose, patients used the drug for 6 weeks cally localized prostate cancer underwent RRP with deliberate Efficacy parameters were the improvement of the IIEF question 3 wide bilateral neurovascular bundle resection and the placement & 4 and the number of erections sufficient for intercourse. of bilateral grafts. RigiScan® testing, a series of erectile dys­ Results: A total of99 patients (mean age 57.9 y, mean duration function questionnaires, a partner questionnaire, and pati_ent of ED SJ y) were non-responders to sildenafil. Eighty five interviews were performed at 3, 6, 12, and 18 (when available) patients had at least 1 administration of EDEX®NJRIDAL® in­ months postoperatively. Only results for those men with a fol­ office, and 66 patients injected at least once at home (ITT low-up of;z:12 months (mean 15 ± 4 months) are presented. population), with a total of 553 injections. Fifty-nine patients Results: Four of twelve (33%) men have had spontaneous, (89.4%) reported an improvement in attaining an erection (IIEF medically unassisted erections sufficient for with vaginal penetration. Three of twelve (25%) men describe Q3) and 56 patients (84.8%) reported an improvement in "40%--60%" (fullness, no rigidity, not able to penetrate) spon­ Fifty-eight patients (87.9%) maintaining an erection (IIEF Q4). taneous erections, 1/11 has a "20%" erection (engorgement), reported erections sufficient for intercourse. There was I serious and 1/11 has distinct RigiScan® erections (but none clinically). adverse event during the treatment with Viagra® (prostate cancer) Overall, 7/12 (58%) men have convincing return of erectile and 1 with EDEX®NIRIDAL® (bladder cancer). These SAEs activity. No demonstrable clinical activity was noted prior to were not related to the study medications. :S:5 months postoperatively. Greatest return of function thus far Conclusion: The results of this trial indicate that the treatment has been observed at 14-18 months postoperatively. with intracavernous alprostadil alfadex is an efficacious and safe Conclusion: Representing a significant potential advance alternative in patients who are non-responders to sildenafil. in prostate cancer surgery, these findings clearly demonstrate a beneficial role ofbilateral nerve graft placement during RRP, when both cavernous nerves have been deliberately resected. Podium presentations

S72 29 30 PENILE ARTERIAL BYPASS IN ARTERIOGENIC IMPOTENCE: USE OF CONTRALATERAL DORSAL INTRASCROTAL RESERVOlR HER.c'\/IATION AS A COMPLICATION OF 3-PIECE PENILE PROSTHESIS ARTERY AS NEOARTERIAL SOURCE. INSERTION: RESULTS OF A PHYSICIAN SURVEY Joel M. Kaufman and Janet L. Kaufman Anoop Sharma, Steve Wilson, and Hossein Sadeghi-Nejad, 1411 S. Potomac, #140, Aurora, CO 80012 Van Buren. AR and Hackensack. NJ. INTRODUCTION AND METHODS: Improvements in design and technique have resulted in fewer complications associated INTRODUCTIO'\· The most common surgical procedure for with inflatable penile prostheses. A review of literature reveals a .-.1rteriogenic impotence involve:::; bypass using inferior epigastric few reports on small and large bowel erosions of prosthesis c1rtery into the dorsal or Jorsal :lrtery beyond a poim of reservoirs. but a paucity of data on the incidence and obstruction. In some cCascs the wntralateral dorsal artery management of intrascrotal reservoir herniation. A multi-item questionnaire addressing various aspects of penile prosthesis appears normal and could serve :1s the donor vessel. We .u,· manaaement was matled to the members of the SSL reporting 10 cases ol" s1rteriogclllc impotence treated by RESULTS: 105 questionnaires (105/275) were received. anastomosis of one dorsal c1ncry tc1 the other. Practice data: Academic 40%. Private 60%. Years in practice: 0-5 METHODS: From 1994-1998 ,33 patients underwent penile (6%) 6-10 (18%) 11-15 (16%) 16-20 (17%) >20 (41%). 11% of to erectile for arteriogenic impotence. In 10 respondents devoted more than 75% of their practice microvascular artery bypass dysfunction. Number of penile prostheses/ year: <5 (28%); 5-10 of 33 men, one dorsal artery was selected as the best recipient (20%); 10-20 (16%); 20-30 (13%); > 30 (23%). 71 respondents vessel and the other dorsal artery served as the donor. Mean age (67%) stated that more than 75% of the prostheses they place are was 31.2 years. Diagnosis was made by DICC or Duplex inflatable. 61 % predominantly use A.J.\1S devices, 39% Mentor. Doppler Ultrasonography. Pudenda! arteriography showed Penoscrotal approach 77%, infrapubic 23%. Nearly all respondents (99%) place the reservoirs in a- paravesical location. obstruction proximal to the dorsal-cavernosal artery bifurcalllln 30 respondents (28%) had experienced reservoir herniation (21 on one side and normal dorsal artery on the other. End-to-end inguinal canal, 6 intrascrotal, 3 ventral.) Of these, 93% used a bypass was used in 9 patients and end-to-side in 1. penoscrotal approach. The total cumulative count for intrascrotal RESULTS: The absence uf an abdominal incision shortened herniation was 3 7 cases over the years. The majority of surgeons elected to approach the herniation from above with closure of the the operative procedure a:1d recovery period. All were done on external ring. A few advocated replacement through the same an outpatient basis. S 1milari ty m vessel diameter facilitated the (penoscrotal) incision in cases were herniation was noted in the microscopic procedure. Mean erectile rigidity (patient estimate) immediate post-operative period. Some reported having left a increased from 59% to 84%. Six patients reported 90-100% reservoir in the mguinal canal or the if the patient remained asymptomatic. Contralateral replacement of the postoperative rigidity, one improved from 40 to 75%, and 3 did reservoir may be associated with development of an inguinal not improve. There were no surgical complications. hernia on the side of original reservoir herniation. CONCLUSIONS: In young men with arteriogenic impotence CONCLUSIONS: Practicing urologists should be fan1iliar with and suitable arteriographic , dorsal to dorsal artery the diagnosis and management of this complication. bypass is an excellent procedure with reduced morbidity and operative time.

31 32 SEXUAL REHABILITATION BY RELE.\SE OF THE Fl1 ,DIFOIOI \;\ll Sl 1SPE:'iSORY LIG,UIENTS OI• IMMEDIATE TIIE PE:'11S F0LL0WINC INFL.\T \llLF PE:'-IILE PROSTHESIS SIMULTANEOUS PLACEMENT OF PENILE 1'-SERTIO, TO \ll:'ilMIZE Tl-IE RISK OF PH.-\LLLS SHORTENING: PROSTHESIS WITH RADICAL PROSTATECTOMY: A SAFE A.'

penile prosthesis 1. IPP) is a common patient concern, especially pcst-:n,·ection. We evaluated release of the ti.mdiform and Since 1993 we have offered placement of a penile prosthesis at suspensory ligar:1ents on flaccid and erect post-IPP length. the time of non-nerve-sparing radical prostatectomy (RRP) as a Patients and Methods: S-+ patients. ages 50-82 (average: <,7 form of immediate sexual rehabilitation. We present here our years) underwent !PP with lig:uncnt release. Pre-op base- results in our initial I 00 patients. penile measurements were obtained in the flaccid and stretched After completion of a non-nerve-sparing radical prostatectomy positions. An infrapuh1c surgical approach was utilized to place the and were closed except for several centimeters of a 3-piece !PP (Alpha-One; \kmor l\1rp., Santa Barbara. C.\ I fascia and skin inferiorly for subsequent placement of the The fundiform and suspensory ligaments of the penis were prosthesis. Drapes, gowns and gloves were then changed, and the identified and incised with electrocautery ac the level of the prosthesis portion of the procedure was performed by a second pLbic ram us. Dethted and inflated (Base-Tip) measurements surgeon. Cefazolin was administered at the beginning of the RRP, were o·otained. :Vkasurements then taken to l6mos (ave:6 mos). followed by vancomycin and gentamicin prior to prosthesis Results: placement. Patients received ciprofloxacin 500 mg bid I Post- Avg. Base-Tip Pre- I Post- I Post- postooperatively until catheter removal on postoperative day 8-9. op incision Op f/u Increase Length !PP Mean followup was 3 years. The mean age was 59.5 years, with a (cm) I (avg l (::l\:g_) (avg.) (avz.) ; (cm) range of 41 to 75 years. Flaccid 8.57 I 9.93 11.14 ! I l.O I 2.-+ There have been no prosthetic infections. Eight patients required Erect 10.71 11.57 12.42 12.-+-+ 1.73 I additional procedures for the prosthesis, consisting of replacement Patient questionnaire revealed 93% satisfaction with I) the for device failure in 3 and correction of angulation in 5. Three of !PP, 2) penile length and 3) willingness to undergo procedure again. Post-operatively, 3 scrotal hematomas developed (all these angulations occurred in the first 12 patients due to resolved spontaneously) and 2 implant infections (Staph. positioning of the penis and catheter in a sharp lateral orientation. aureus) required device removal. No cases of penile numbness PSA recurrence was noted in 6 men. Two men have been treated or shortening have been reported to date. for bladder neck contractures. Conclusions: This pre:iminar; data suggests release of the These results demonstrate that immediate sexual rehabilitation fundiform and suspensory ligaments following !PP is safe and with penile prosthesis at the time of radical prostatectomy can be effective in minimizing tr.e r:sk of shortening. Further performed safely, with minimal risk of prosthetic infection, and lono-t~m, follow.1m ic:. rPni1irPfl without compromising surgical treatment of prostate cancer.