The direction and severity of penile curvature does not have an impact on concomitant vasculogenic erectile dysfunction in patients with Peyronie's disease.

Although the association between Peyronie's disease (PD) and erectile dysfunction (ED) is well established, limited data are available correlating penile curvature and penile hemodynamic parameters. We sought to examine this association in a cohort of PD men undergoing penile duplex Doppler ultrasound (PDDU). PD patients were retrospectively evaluated to correlate the extent and direction of penile curvature with measured vascular parameters. Demographic variables, disease characteristics and PDDU parameters were tabulated and statistically compared based on extent (≤ 45° and >45°) and direction (dorsal, ventral, lateral, ventrolateral, dorsolateral) of curvature. A total of 220 PD patients (mean age of 55.0 ± 9.2 years) underwent PDDU at one institution from January 2008 to December 2010. Overall, 69.5% of patients were found to have vasculogenic ED (arterial insufficiency (AI): 10%; veno-occlusive dysfunction (VOD): 43.2%; AI + VOD: 16.4%). Mean curvature was similar among all PDDU groups (AI: 41.7 ± 5.2°; VOD: 41.3 ± 2.5°; AI+VOD: 37 ± 4.1°; no-ED: 37.3 ± 3°; P > 0.85). No significant differences were noted in the presence or type of ED among various directions of curvature (P = 0.34) or when curvatures were stratified by ≤ 45° and >45°. The direction and extent of penile curvature are not associated with altered rates of vasculogenic ED on PDDU in PD patients.

Initial evidence demonstrating the association between the vascular status in surgically resected renal parenchymal pathology and sexual function.

Our goal is to evaluate the association between histopathology of glomerulosclerosis (GS) and atherosclerosis (AS) in the nephrectomized normal parenchyma together with patients' background, and erectile dysfunction (ED) of patients treated with radical nephrectomy (RN) for renal cell carcinoma (RCC). ED was assessed with the International Index of Erectile Function in 65 patients who were less than age 70 years at the time of questionnaire. Glomeruli status was assessed by the extent of global GS. AS was graded based on lumen occlusion and frequency of involvement. Patients' backgrounds included any comorbidities, post-RN renal insufficiency, tumor pathology, demographics and social status. The presence of diabetes mellitus and lack of a spouse were independent predictors for severe ED, whereas G0/1 AS was an independent predictor for mild/no ED. The extent of global GS was significantly lower in patients with mild/no ED than in other patients. Our study represents the first report identifying healthy arterial status in the renal parenchyma as a significant indicator of favorable erectile function and that the evaluation of AS severity is not a superior indicator of severe ED in the presence of comorbidities or social status among patients treated with RN.

Outcomes of crural ligation surgery for isolated crural venous leak.

INTRODUCTION: Venous ligation surgery results for diffuse venous leak have been disappointing, although in isolated crural venous leak (ICVL) cases, efficacy for crural ligation surgery (CLS) has been demonstrated. AIM: The purpose of this study was to present our experience with treatment of ICVL with CLS. METHODS: All patients underwent preoperative cavernosometry. Cavernosography (CG) or perineal compression (PC) was used to define the diagnosis of ICVL. If CG demonstrated ICVL or flow-to-maintain values normalized with PC, the patient was counseled regarding CLS. Baseline and postoperative erectile function (EF) was assessed by the International Index of Erectile Function (IIEF) questionnaire. MAIN OUTCOME MEASURES: EF, using the EF domain (EFD) score of the IIEF, a domain with six questions with a maximum score of 30 and a minimum score of 6 in the sexually active male. All patients completed the questionnaire preoperatively and in a serial fashion after surgery at a time point after 12 months postoperatively. RESULTS: 14 patients underwent CLS. Mean age was 29 ± 7 years. Also, 64% had primary erectile dysfunction. Mean baseline IIEF-EF score was 18 ± 6. Furthermore, 71% of patients had failed phosphodiesterase type 5 (PDE5) inhibitors and 6/10 (60%) failed intracavernosal injections (ICI). Mean postoperative EFD score was 24 ± 3 representing a mean change of 6.5 points per patient. No patient needed ICI after CLS; however, 4/14 patients needed PDE5 inhibitors, all of whom had been using ICI preoperatively. In addition, 71% experienced unassisted sexual intercourse after CLS. CONCLUSIONS: In a highly selected population of young men with ICVL, CLS cures 70% and improves EF in more than 90% of men. Surgical treatment of ICVL by CLS can be performed safely and with sufficient efficacy that larger and longer term studies should be undertaken.

PARP inhibition restores erectile function by suppressing corporal smooth muscle apoptosis in diabetic rats.

INTRODUCTION: An important mechanism suggested to be responsible for diabetes-associated erectile dysfunction (ED) involves increased apoptosis, increased collagen deposition, and reduced smooth muscle content in the corpus cavernosum. AIM: To determine whether the activation of the pro-apoptotic poly(adenosine diphosphate ribose) polymerase (PARP) pathway is involved in the induction of corporal apoptosis, and whether the administration of 3-aminobenzamide (3-AB), a specific PARP inhibitor, could ameliorate ED in diabetic rats. METHODS: Male Sprague-Dawley rats (8-weeks-old) were randomly divided into three groups: age-matched controls (C), diabetic controls (DM), and 3-AB-treated diabetic group (DM + 3-AB). Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50 mg/kg). Eight weeks after the induction of diabetes, DM + 3-AB group treated with 3-AB (30 mg/kg/day, ip) for 4 weeks. MAIN OUTCOME MEASURES: At 12 weeks after diabetes induction, erectile function was assessed by cavernous nerve stimulation. Penile tissue was assessed for apoptosis, Masson's trichrome stain and immunohistochemical analysis for smooth muscle alpha actin. Expression of poly(ADP-ribose), phospho-protein kinase B (Akt), phospho-Bcl-2-associated death promoter (Bad), B-cell leukemia/lymphoma 2 (Bcl-2), Bcl-2-associated X Protein (Bax), and apoptosis-inducing factor (AIF) were evaluated by Western blot. Caspase-3 activity and malondialdehyde (MDA), adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide (NAD+) concentrations were also determined. RESULTS: DM group showed impaired erectile function, increased PARP activity and corporal apoptosis, and decreased smooth muscle contents. Expression of phospho-Akt, phospho-Bad, Bcl-2, and concentrations of ATP and NAD+ were decreased in the DM group, whereas concentrations of MDA, expression of Bax, nuclear translocation of AIF, and caspase-3 activity were increased. Treatment with 3-AB restored erectile function and significantly reversed all molecular and histological alterations except for the increased MDA. CONCLUSION: Over-activation of penile PARP pathway in diabetic rats enhances corporal apoptosis via energy depletion, suppression of Akt phosphorylation, and activation of the mitochondrial apoptotic pathway, which results in ED; these event could be prevented by treatment with 3-AB.

Impact of metabolic syndrome on erectile dysfunction and lower urinary tract symptoms in benign prostatic hyperplasia patients.

INTRODUCTION: The aim of this study was to investigate the relationship among metabolic syndrome (MetS), erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). METHODS: Our study included 106 patients with BPH, 33 (31.1%) of whom had MetS. Blood pressures, waist circumferences, serum levels of fasting blood glucose, high density lipoprotein and triglyceride of patients were recorded. Erectile functions of the patients were evaluated by International Index of Erectile Function (IIEF). Patients were divided into two groups according to IIEF scores, namely 'mild/no ED' and 'moderate/severe ED'. IIEF scores of ED groups were between 17 and 30 and 6-16 in turn. LUTS severities were assessed by International Prostate Symptom Score (IPSS) and classified as mild (IPSS 0-7), moderate (IPSS 8-19) and severe (IPSS 20-35). RESULTS: There was a significant difference between ED groups concerning MetS presence (p=0.032). MetS presence was not found to be associated with the severity of LUTS (p=0.144). There was no correlation between ED groups regarding LUTS severity (p=0.303). CONCLUSION: Results of the present study showed a correlation between MetS presence and ED. In the light of our results, MetS seems to play an important role in the etiopathogenesis of ED in patients with BPH.

[Nebido in the treatment of hypogonadism syndrome and its complications in men].

The article presents original experience with use of undecanoate (nebido, BayerHealthcare Pharmaceuticals, Germany) in androgenic testosteron replacement therapy in males with hypogonadism. Prospective studies of nebido efficacy were made in males with vein-occlusive erectile dysfunction (n = 20), chronic pelvic pain syndrome (n = 77), metabolic syndrome (n = 170). Retrospective studies assessed efficacy of nebido monotherapy in patients with erectile dysfunction and hypogonadism (n = 34), hematological and urological safety of the drug (n = 40). Laboratory monitoring was performed in all the studies according to ISSAM recommendations. The patients were not included in contraindications to androgenic therapy. Nebido treatment significantly improved libido and erectile function, efficacy of phosphodiesterase of type 5 inhibiors used in moderate and severe erectile dysfunction. Depressive, asthenic, pain symptoms declined in males with chronic pelvic pain. Body fat reduced in metabolic syndrome with alleviation of its other components. Insignificant rise of hemoglobin level and packed cell volume was observed in some patients while a PSA level increase was clinically significant in 10% patients who had initial PSA > 2.5 ng/ml and acromegalia. Also, nebido depressed production of gonadotropins and spermatogenesis. Thus, nebido is highly effective in sexual dysfunction and other somatic disorders caused by hypogonadism. Nebido does not induce severe side effects, but clinically significant rise of PSA level requires treatment discontinuation and more careful urological examination. In view of nebido ability to suppress spermatogenesis, the drug should not be used in reproductively active men.

Summary of the recommendations on sexual dysfunctions in men.

INTRODUCTION: Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. AIM: To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. METHODS: An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures. New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. RESULTS: Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men's and women's individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie's disease; and priapism. CONCLUSIONS: Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

The use of high-resolution magnetic resonance imaging in the management of patients presenting with priapism.

OBJECTIVE: To investigate the use of magnetic resonance imaging (MRI) of the penis during an episode of priapism and assess the viability of the corpus cavernosum (CC) smooth muscle, as prolonged ischaemic priapism is associated with a high rate of long-term erectile dysfunction (ED), and the viability of CC smooth muscle influences the subsequent management in ischaemic priapism. PATIENTS AND METHODS: The study was set in a single centre based in a large university teaching hospital. We investigated the correlation of T2-weighted gadolinium- enhanced MRI with the histology from CC biopsies in the same patients. In all, 38 patients (mean age 42 years) presenting with priapism over a 3-year period had MRI of the penis. The scans were reported by two dedicated uro-radiologists who graded the MR images as showing viable or nonviable erectile tissue. One pathologist assessed the CC biopsies for necrosis. The findings were then correlated. Where no biopsies were taken a clinical follow-up was used to assess erectile function. RESULTS: In 23 patients undergoing both a CC biopsy and MRI, the sensitivity of MRI in predicting nonviable smooth muscle was 100%. In a further 10 patients MRI showed nonviable CC smooth muscle, but no biopsy was taken in these patients; on clinical follow-up all of these patients subsequently developed ED. In a further five patients the imaging showed viable smooth muscle and these patients subsequently maintained erectile function on clinical follow up. CONCLUSIONS: Penile MRI provides an accurate imaging method to assess smooth muscle viability in patients presenting with priapism.

The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model.

INTRODUCTION: Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. AIM: To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. METHODS: Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2'-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function, and penile histology. MAIN OUTCOME MEASURES: Erectile function was assessed by intracavernous pressure (ICP) measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. RESULTS: Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. CONCLUSIONS: Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED.

Characterization of VEGF and angiopoietins expression in human corpus cavernosum during aging.

INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated. AIM: To characterize the vascular organization, concomitantly with analysis of the expression of vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2) in young and aged human corpus cavernosum. METHODS: Human penile fragments were removed from patients submitted to penile deviation surgery (11 cases; 58-70 years) and from potential organ donors (four cases; 18-28 years) without ED or risk factors for ED. Smooth muscle and connective tissue were assessed by Masson's trichrome staining and computer-assisted histomorphometry. Dual immunostaining for specific markers of endothelium (von Willebrand factor) and smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence microscopy. Semi-quantification of expression of angiogenic factors was performed by Western blotting. MAIN OUTCOME MEASURES: Expression of VEGF and Angiopoietins in human corpus cavernosum, using a combination of histologic stainings, and molecular biology tools in order to achieve a better understanding of cavernosal tissue remodeling with aging. RESULTS: Aged human corpus cavernosum presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle cell cytoplasm with identical localization in both studied groups. VEGF expression was abundant in smooth muscle cell and its expression markedly decreased in aged tissue, contrasting with the expression of angiopoietins that increased in the aged corpus cavernosum. CONCLUSIONS: Immunoflourescent studies of cellular markers and growth factors help clarifying vascular organization and angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the organization pattern of vascular endothelium and smooth muscle components of cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged penile tissue suggest a VEGF-independent vascular remodeling mechanism.

Role of adenosine signaling in penile erection and erectile disorders.

INTRODUCTION: Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection. AIM: To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders. MAIN OUTCOME MEASURES: Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism. METHODS: The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism. RESULTS: Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A(2B) receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism. CONCLUSION: Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism.

Penile revascularization for erectile dysfunction: a systematic review and meta-analysis of effectiveness and complications.

INTRODUCTION: Patients with arteriogenic erectile dysfunction (ED) caused by traumatic localized arterial lesions can be treated successfully by penile revascularization (PR) surgery. We aimed to determine the subjective and objective outcomes of PR surgery in patients with arteriogenic ED. MATERIALS AND METHODS: We searched for relevant publications released up to May 2008 in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Biological Abstracts. The citation lists of review articles and included trials were also searched. Published studies on different operative techniques of PR for men with ED due to traumatic penile arterial lesions were selected by 2 reviewers. Data on participants' characteristics, study quality, population, intervention, cure and adverse effects were collected and analyzed. RESULTS: There were 25 studies that compared the selected operative techniques. Concerning subjective cure, the results in men younger than 30 years old were better than older ones (odds ratio, 3.7; 95% confidence interval, 2.2 to 6.4; P = .001). Venous leak (odds ratio, 1.8; 95% confidence interval, 1.2 to 2.6) and history of smoking (odds ratio, 3.4; 95% confidence interval, 2.2 to 5.6) influenced success rate. Inconsistent measurements of outcomes limited the findings, and none of the studies were randomized controlled trials. CONCLUSION: Traumatic patients with arteriogenic ED might benefit from PR. Patient selection is vital for a successful outcome. Variations in penile vascular anatomy are also likely to be important when individualizing penile revascularization procedures. In a limited number of highly selected individuals PR can be successful for the long-term. Randomized controlled trials examining PR techniques are warranted.

Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat.

OBJECTIVE: To determine whether skeletal muscle-derived stem cells (MDSCs) convert into smooth muscle cells (SMCs) both in vitro and in vivo, and in so doing ameliorate the erectile dysfunction (ED) of aged rats, and whether endogenous stem cells are present in the rat corpora cavernosa. MATERIALS AND METHODS: MDSCs were obtained from mouse muscle, and shown by immunocytochemistry for alpha-smooth muscle actin (alpha SMA) to originate in vitro in myofibroblasts and SMCs, discriminating SMCs by calponin 1 expression. In vivo these MDSCs, labelled with 4',6-diamidino-2-phenylindole, were implanted into the corpora cavernosa of young adult (5-month old) and aged (20-month old) rats for 2 and 4 weeks. Histological changes were assessed by immunohistochemistry and quantitative Western blot. Functional changes were determined by electrical field stimulation (EFS) of the cavernosal nerve. RESULTS: The exogenous cells replicated and converted into SMCs, as shown in corporal tissue sections by confocal immunofluorescence microscopy for proliferating cell nuclear antigen (PCNA), alpha SMA, and smoothelin, and also by Western blot for alpha SMA and PCNA. MDSC differentiation was confirmed by the activation of the alpha SMA promoter-linked beta-galactosidase in transfected cells, both in vitro and after implantation in the corpora. Putative endogenous stem cells were shown in corporal tissue sections and Western blots by detecting CD34 and a possible Sca1 variant. EFS showed that implanted MDSCs raised in aged rats the maximal intracavernosal pressure/mean arterial pressure levels above (2 weeks) or up to (4 weeks) those of young adult rats. CONCLUSIONS: MDSCs implanted into the corpora cavernosa of aged rats converted into SMCs and corrected ED, and endogenous cells expressing stem cell markers were also found in untreated tissue. This suggests that exogenous stem cell implantation and/or endogenous stem cell modulation might be viable therapeutic approaches for ageing-related ED.

Circulating endothelial progenitor cells correlate with erectile function in patients with coronary heart disease.

AIMS: The aim of the study was to determine the influence of endothelial progenitor cells (EPC) on erectile dysfunction (ED). EPC play a major role in repair mechanisms of the endothelial monolayer, but the role of EPC in ED is unclear. METHODS AND RESULTS: Circulating levels of CD34(+)/KDR(+) and CD133(+) EPC were determined in 119 patients with known coronary artery disease. ED was evaluated with an ED-score generated from the KEED questionnaire. Prevalence of ED was 59.7%. In univariate analysis, age, hypertension, reduced left ventricular ejection fraction (LVEF), diabetes, and circulating levels of CD133(+) EPC, but not cardiovascular drug treatment were associated with ED. Body mass index (BMI) was positively (r = 0.319, P=0.003) and high-density lipoprotein was negatively (r=-0.246, P=0.034) correlated with ED. Adjustment for age, diabetes, hypertension, BMI, smoking, LVEF, use of statins and lower urinary tract symptoms, and prior coronary intervention revealed low levels of circulating immature CD133(+) EPC as independent risk factor for ED (95% CI -11.183 to -1.7371, P=0.008). CONCLUSION: Reduced levels of circulating CD133(+) EPC are an independent risk factor for ED. Thus, EPC may be a link between cardiovascular risk factors, endothelial dysfunction, and ED.

Congruence between veno-occlusive parameters during dynamic infusion cavernosometry: assessing the need for cavernosography.

While dynamic infusion cavernosometry (DIC) is being performed with increasing rarity, some centers continue to use this investigation modality. Cavernosography may be utilized to identify the location of patent venous channels in men with venous leak. In an era when venous ligation surgery is being performed with less frequency, the role of cavernosography has been questioned. This study was conducted to define the congruence between the three parameters (flow-to-maintain (FTM), pressure decay (PD) and cavernosography) used in the diagnosis of venous leak during DIC. Established values for the three parameters were utilized and the diagnosis of venous leak was based upon the FTM measurement. All studies were performed using a vasoactive agent-redosing schedule. Cavernosography was conducted using a nonionic contrast agent at an intracorporal pressure of 90 mmHg. In patients with an elevated FTM value, 24% had a normal PD recorded, all of whom had FTM values <10 ml/min. The Pearson correlation coefficient for the relationship between FTM and PD was 0.58 (P=0.025). In all, 36 patients (54%) had an abnormal cavernosogram (CG). All patients who had positive findings on CG had elevated FTM values. On the other hand, 46% of patients with abnormal FTM values had a normal CG. This analysis indicates that almost one-half of men with venous leak diagnosed at the time of DIC based on FTM measurement will fail to have any veins visualized on cavernosography. These data further undermine the value of cavernosography, particularly in men with low-grade venous leak.

The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia.

PURPOSE: We examined neurogenic and vasculogenic erectile dysfunction associated with hypercholesterolemia and evaluated vascular endothelial growth factor (VEGF) and adeno-associated virus (AAV) mediated, brain derived neurotrophic factor (BDNF) for potential treatment. MATERIALS AND METHODS: A total of 21, 2-month-old male rats were fed a 2% cholesterol diet and another seven were fed a normal diet. Two months later serum cholesterol levels were measured and test agents were given intracavernously. Those on normal diet (controls) received phosphate buffered saline (PBS). Those on cholesterol diet were randomly divided into 3 groups receiving PBS, VEGF (4 microg.) or AAV-BDNF (10 viral particles). Four months later erectile function was evaluated and cavernous tissues were collected for erectile dysfunction and immunohistochemical staining. RESULTS: Serum cholesterol levels were higher in rats fed the high fat diet than in controls. Intracavernous pressure was lower in cholesterol plus PBS treated rats than in rats of the other 3 groups. All hypercholesterolemic rats had less nerve content, fewer endothelial cells and higher smooth muscle content than rats with normal cholesterol levels. In cholesterol plus PBS treated rats electron microscopy showed hypermyelination and severe atrophy of axons, a remarkable decrease in the number and size of nonmyelinated axons, disarray of the smooth muscle cells with scant myofilaments and foamy cytoplasm, and denuded endothelial lining of the sinusoids covered by numerous platelets. VEGF and AAV-BDNF appeared to alleviate partially these changes. CONCLUSIONS: A high fat diet caused erectile dysfunction with accompanying neurological and vascular changes. VEGF and AAV-BDNF seemed to alleviate these problems.

Cavernosal arterial anatomic variations and its effect on penile hemodynamic status.

OBJECTIVE: With continuous improvements in ultrasound technology, small vessels with remarkably slow blood flow that may not be assessed by color Doppler ultrasonography, can be evaluated using power Doppler ultrasonography. In the present study, penile arterial anatomic variations were determined with power Doppler ultrasonography and its impact on penile hemodynamic status. METHODS: A total of 54 patients with erectile dysfunction were evaluated with power Doppler ultrasonography. The effects of vascular anatomic variations and the structure of the corpora cavernosa and tunica albuginea on vascular status were assessed on both sides. RESULTS: A normal penile vascular system was observed in 35.2% and 25% of 54 patients (mean age: 46.6+/-11.5 years) at the radix and mid-shaft of the penis, respectively. Pure arterial component was observed in 40.7% (22/54) and 47.2% (17/36) of the patients at the base and mid-shaft of the penis, respectively. Penile arterial insufficiency was severe in 9.2 and 5.5% of the patients at the base and mid-shaft of the penis, respectively, whereas intrapenile truncus was found in six patients (5.5%), the ratio of single cavernosal artery, intrapenile and extrapenile bifurcations were 69.4, 7.4 and 12.0%, respectively. Twenty (18.5%) dorso-cavernosal perforators, 15 (13.9%) cavernoso-dorsal and 30 (27.8%) intercavernosal branches were found. Peak systolic blood flow velocity values were decreased in 12 of 36 patients (33.3%) distally, while increased blood flow was observed in 11 (30.5%). CONCLUSIONS: Hemodynamic parameters might be variable at either side of the penis and depend on intrapenile arterial anatomic variations. Parameters determined using power Doppler ultrasonography should be evaluated from the proximal to distal side of the penis to obtain reliable and standard results. However, variations of penile arterial anatomy and its effect on penile hemodynamic changes should not be overlooked especially in the patients who are candidates for penile reconstructive or vascular surgery.

Long-term results of dorsal penile vein ligation for symptomatic treatment of erectile dysfunction.

About 20% of patients with erectile dysfunction do not react to intracavernous pharmacological treatment (SKAT) because of a cavernous leak. The first attempt to treat venous insufficiency goes back as far as the beginning of the century. Ligature and resection of the superficial and deep veins of the penis (DPVL) were performed in 122 patients (nonresponders to SKAT with a maintenance flow of less than 40 ml min-1). Twenty-four patients suffered from primary dysfunction and 98 from secondary dysfunction. The average age of the patients was 49 years, and the average duration of the preoperative erectile dysfunction 4.4 years. Postoperative follow-up was carried out for 70 months. In 98% of the patients, cavernosography revealed a dorsal leak. Twenty-six per cent had ectopic veins, 38% a leakage through the crural veins and 24% a glandular or spongiosal shunt. After the 70-month follow-up, only 14% of the 122 patients were able to achieve an adequate spontaneous erection and 19% also responded to SKAT. Depending upon the time elapsed since the operation, the rate of spontaneous reaction was reduced. It was found that younger patients with a short history of erectile dysfunction, no arterial cofactor, a maintenance flow of less than 100 ml min-1 and a severe dorsal leakage from a DPVL were the most likely to benefit from this procedure. Since degeneration of smooth muscle cells of the cavernosa is in most patients the cause of the venous leakage, penis vein surgery is to be regarded as symptomatic treatment.

Electron microscopic findings of penile tissues in veno-occlusive dysfunction: is penile biopsy necessary?

In this study, we examined the biopsy patterns of penile tissues taken during operation from patients subjected to surgical treatment for veno-occlusive dysfunction, and evaluated the importance of penile biopsy. We evaluated the findings from 17 patients with venous impotence. Fourteen of them underwent total vein ligation and the rest penile prosthesis implantation. Tissue specimens taken from superficial and deep dorsal veins, tunica albuginea and corpus cavernosum during operation were examined under electron microscope. Tissue specimens taken from 3 cadavers were used as the control group. Although the deep and superficial vein specimens of all patients did not show significant differences, oedema and increase of fibroblasts in collagen fibres of the corpus cavernosum and tunica albuginea were demonstrated. We concluded that penile biopsy as an invasive method does not give enough information about the choice of treatment for erectile dysfunction.

Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction.

PURPOSE: Reliable, clinically available, non-invasive measurements able to predict trabecular histology without the need for erectile tissue biopsy would improve impotence management, since the percentage of trabecular smooth muscle content has been shown to be associated with corporal veno-occlusive dysfunction. The purpose was to identify whether the erectile tissue mechanical property, cavernosal expandability, correlated with the percentage of trabecular smooth muscle content in an animal model of hypercholesterolemia and ischemic-induced corporal fibrosis. MATERIALS AND METHODS: New Zealand White rabbits (6 to 7 months old, 3 to 3.5 kg.), were divided into control (n = 7), hypercholesterolemic (n = 5, 0.5% cholesterol diet) and atherosclerotic groups (n = 8, 0.5% cholesterol diet with balloon de-endothelialization). At 16 weeks, the corpora cavernosa were removed en bloc and submerged in physiologic salt solution, and volume-pressure data were plotted at 20 mm. Hg pressure intervals under trabecular smooth muscle relaxation. Cavernosal expandability, X, (the measure of the ability to achieve high corporal expansion at relatively low intracavernosal pressure) and tunical distensibility, V(E)/V(F), (relative volume of fully erect to flaccid penis) were calculated. Erectile tissue was assessed by computer-assisted color histomorphometry with Masson's trichrome stained sections (30 to 45 high power fields/animal) to assess percentage of trabecular smooth muscle content. RESULTS: The overall mean percentage of trabecular smooth muscle content and mean cavernosal expandability values were 45.4 +/- 1.6, 39.2 +/- 0.9, 33.9 +/- 0.6 and 0.0165 +/- 3.04 x 10(-3), 0.0116 +/- 1.63 x 10(-3), 0.0118 +/- 1.26 x 10(-3) mm. Hg(-1) for the control, hypercholesterolemic and atherosclerotic groups, respectively (r = 0.87). Significant differences in trabecular smooth muscle content were observed among all 3 groups, and in cavernosal expandability, between control and atherosclerotic groups, as well as between control and hypercholesterolemic groups but not between atherosclerotic and hypercholesterolemic groups. CONCLUSIONS: The erectile tissue mechanical property, cavernosal expandability, correlated with erectile tissue structural quality. Since cavernosal histology has been shown to predict corporal veno-occlusive function, it is hypothesized that the measurement of cavernosal expandability may become a valuable functional clinical parameter in the diagnosis and treatment of men with erectile dysfunction.