The value of corpus cavernosum electromyography in erectile dysfunction: current status and future prospect

In the last decade, several investigators have tried to develop corpus cavernosum electromyography (CC-EMG) as a direct clinical method to evaluate the state of the penile autonomic innervation and the cavernous smooth muscle. Both basic and clinical studies have shown promising results. However, its application as a diagnostic tool with clinical relevance was hindered by insufficient knowledge of cavernous smooth muscle electrophysiology, lack of standardization, technical and practical difficulties and problems in the interpretation of the results. Recently, the European Commission created the so-called COST Action B18 (corpus cavernosum EMG in erectile dysfunction), aiming to strengthen the coordination of the European research groups and give the development of CC-EMG a new impetus. This review presents an overview of the physiological background, the current status of CC-EMG, and discusses possibilities for further developments.     

Overactive corpus cavernosum: a novel cause of erectile dysfunction

Our recording of the electromyographic (EMG) activity of the corpus cavernosum (CC) in 59 patients with erectile dysfunction (ED) revealed 18 patients who had elevated electric activity, which presumably points to heightened tone of the CC smooth muscles. We investigated the hypothesis that this elevated EMG activity and muscular tone of the CC could be the cause of ED. The study comprised the said 18 subjects with the hypertonic CC muscles as study group (42.6 +/- 5.3 SD years), 15 healthy volunteers (41.8 +/- 5.1 SD years) and 15 patients (41.6 +/- 5.5 SD years) with ED who had not recorded elevated tone of the CC muscles as control group. The EMG activity was registered in the flaccid, erectile and detumescent phases by two electrodes inserted into the CC. Electrocavernosography (ECG) of healthy volunteers recorded in the flaccid phase showed regular slow waves (SW) and random action potentials (APs). The wave variables declined significantly in the erection phase (P < 0.01). In the study group, the SW variables in the flaccid phase increased significantly (P < 0.05) compared with the healthy volunteers and the rhythm was irregular. Erection did not occur with sildenafil but with intracavernosal injection of papaverine, which led to decline of the SW variables (P < 0.05). The control ED group exhibited in the flaccid phase diminished SW variables (P < 0.05) compared with the healthy volunteers. On erection with sildenafil administration, the SW variables showed significant reduction (P < 0.05). CC hypertonicity or 'overactive CC' was identified as a possible cause of ED. An elevated EMG activity of the CC muscle fibres in the flaccid phase presumably denotes hypertonicity of these fibres and their failure to relax to effect erection. The cause of elevated CCEMG activity and presumed muscle hypertonicity is unknown and could be functional or organic. Erection was produced by intracavernosus injection of papaverine and not by sildenafil. This condition of 'overactive CC' should be considered in the diagnosis of ED. However, further studies in the pathogenesis of the condition are warranted.     

缺氧性ED模型阴茎海绵体微结构改变的研究进展

缺氧是勃起功能障碍(ED)的独立危险因素,其导致ED的机制复杂多样,传统的研究更多关注阴茎海绵体内皮、体内性激素水平的改变,但近年来此方面的研究未有突破性进展。近期研究表明,阴茎海绵体微结构的改变,如收缩型阴茎海绵体平滑肌细胞表型转换、海绵体的纤维化可能是缺氧性ED发生的重要机制。而针对阴茎海绵体微结构改变的一些手段,如基因治疗、干细胞治疗、诱导细胞自噬等有可能为缺氧性ED的治疗带来广阔前景。     

Apoptosis of corpus cavernosum in patients with organic erectile dysfunction

Objectives  It has been reported that apoptosis of penile erectile tissue occurs after penile denervation, castration, and diabetes mellitus in animal studies. Aim of this study was to investigate apoptosis in corpora cavernosa of patients with organic erectile dysfunction (ED). Methods  Cavernous biopsies were obtained from 38 patients with erectile dysfunction and 10 patients with normal erectile function. Apoptosis of tissues were determined via terminal deoxyuridine nucleotide end labeling method by using flow cytometry. Results  The mean ages of patients with ED and control patients were 50.65 ± 2.27, and 32.43 ± 2.90 years, respectively (P = 0.0001). Patients with ED were set in two groups as more than 50 years old and less than 50 years old for further analysis of age factor on apoptosis. The mean % apoptosis of ED patients was 26.22 ± 2.79 and control group was 11.26 ± 3.79, (P = 0.032). Mean fluorescence intensity (MFI) values were also 17.41 ± 3.21 and 6.59 ± 2.28, respectively (P = 0.039). MFI and % apoptosis values were not statistically significant different neither between the patients groups nor between the control and patients ≤50 years old (P > 0.05). Conclusions  We did not find any statistically significant difference with respect to apoptosis rates when we compared neither control group with ≤50 years old patients nor patients groups of ED. Because of this we did not have enough data to say that apoptosis has a prominent role on the development of ED independently from other factors. However, further studies are necessary to clarify the role of apoptosis in erectile dysfunction.     

Electrocavernosogram in erectile dysfunction: a diagnostic tool

Corpora cavernosa (CC) evoke electric waves that appear to be of diagnostic significance in evaluation of erectile dysfunction (ED). We investigated the hypothesis that electrocavernosography (ECG) exhibits different patterns in the various types of ED: neurogenic, vasculogenic, and psychogenic. Electrocavernosography was performed in the flaccid phase in 16 neurogenic, 28 vasculogenic (15 arteriogenic, 13 venogenic), and 24 psychogenic patients with ED, and in 15 healthy volunteers (controls). Two needle electrodes were introduced into the CC and the EMG activity was recorded in each of the 2 CCs of the same subject. Two 20 minute recording sessions were performed for each subject. The controls recorded slow waves (SWs) with regular rhythm and identical frequency, amplitude and conduction velocity from the 2 electrodes of the same subject. Random action potentials (APs) were superimposed on or followed the SWs. The ECG in the neurogenic ED recorded no waves in 14/16 patients and occasional irregular waves in 2. The SWs of the arteriogenic ED had irregular rhythm and variable and low parameters compared to those of the controls. The ECG of the patients with venogenic ED was similar to that of the controls, while the ECG of the psychogenic ED exhibited SWs with irregular rhythm and higher parameters than the controls. The study has revealed various ECG patterns in ED: "silent" in neurogenic. "bradyarrhythmic" in arteriogenic, "normal" in venogenic, and "overactive" in psychogenic ED. We suggest that electrocavernosography has the potential to function as an investigative tool in diagnosing the type of ED provided further studies are performed to verify the described findings.     

Long-term results of corpus cavernosum autoinjection therapy for chronic erectile dysfunction

Between May 1985 and March 1992, 172 patients suffering from chronic erectile dysfunction (21-70 years old) underwent constant corpus cavernosum autoinjection therapy (CAT) with a standardized papaverine phentolamine mixture (16385 injections). Thereafter 41 patients continued CAT with the single agent papaverine (1257 injections). On the basis of both these 17642 protocol auto-injections, and over 6 years of experience with intracavernosal autoinjection therapy we conclude that, especially with the papaverine-phentolamine mixture, CAT constitutes an effective therapy (full rigidity in 95.8%) with tolerable side-effects for chronic erectile dysfunction when preceded by careful patient selection and thorough multi-disciplinary evaluation. This is especially so in the case of arterial and/or neurogenic aetiology of the erectile dysfunction. In addition, the contraindications must be strictly observed, the treatment and technique fully explained, and a regular follow-up instituted. CAT is generally well accepted by the patients and their partners (98.8%/97.6%) and has distinct positive effects on self-esteem (77.8%), performance anxiety (84.4%), and partnership (79.5%). The most serious side-effect was prolonged erection (25 out of 17642 injections). In 6 patients reversible fibrotic changes near the tunica albuginea were observed.     

Results and acceptance of corpus cavernosum autoinjection therapy in organic erectile dysfunction

Ambulatory autoinjection therapy of the corpus cavernosum with a vasoactive drug combination for vasculogenic and neurogenic erectile dysfunction was performed in 50 men from 10/85-6/87. Acceptance was excellent by all patients and their wives. Transitory hematomas appeared in 6/50 (12%) cases. Local infections, cavernitis or systemic side effects were not observed. In 3/50 (6%) patients prolonged erections occurred. Treatment included drainage of the intracavernous blood, manual decompression and if necessary additional application of 1 mg metaraminol under extreme caution. Only 1 (2%) patient developed a nodular tunica fibrosis at the injection site which disappeared spontaneously upon cessation of treatment within 4 weeks.     

Acceptance of corpus cavernosum auto-injection therapy in long-term treatment of erectile dysfunction]

A total of 121 patients suffering from erectile dysfunction were evaluated by means of a questionnaire. In all these cases corpus cavernosum autoinjection therapy had been recommended. The aim of the study was to determine the acceptance and complications of the therapy, general level of satisfaction with it, and reasons for refusal. Completed questionnaire were received from 89 patients (75.5%), 56.2% of whom had applied the therapy continuously, while 18% had broken it off and 25.8% had never started on therapy (cumulative dropout rate 43.8%). The complications encountered were temporary hematomas (25.8) and deviations of the penis (10.1%). In 6.1% indurations of the penis were found. The frequency of prolonged erection needing an antidote was 0.07% in the continuous treatment group. The relatively high drop-out rate in the autoinjection therapy group shows the necessity for intensive patient care and the need for alternative therapy options and a more critical view of reports already published of success with autoinjection therapy.     

The methodology of corpus cavernosum electromyography revisited

OBJECTIVE: The methodology of corpus cavernosum electromyography (CC-EMG) was revisited, in order to overcome current methodological difficulties that hinder its clinical application. MATERIALS AND METHODS: Using an 8-channel device, CC-EMG was performed in 12 healthy volunteers. Surface electrodes were placed bilaterally on the penile shaft and the kneecap (reference electrode), the pubis region and the anterior superior iliac spine (ASIS). A band pass filter with cut-off frequencies of 0.1 and 20 Hz was used. At least 2 sessions of recordings were performed in each subject. RESULTS: Thirty-five of 46 recordings were interpretable. Significant time delays between potentials recorded from different sites of the CC were detected. Clear spatial voltage gradients related to CC-potentials were observed on the pubis region. No voltage changes related to CC-potentials, but electrical activity from other sources were recorded from the ASIS. In contrast to frequency, a clear correlation could be demonstrated between amplitude, duration and polyphasity of CC-potentials recorded in 2 different sessions in the same individual. CONCLUSIONS: Multichannel monopolar recording of CC-EMG with surface electrodes is practical and has several advantages compared with bipolar recording. The results provide evidence that the recorded signals indeed reflect electrical activity of the CC and therefore offer a basis to pursue further clinical validation studies.     

Virtual cavernoscopy: a novel diagnostic tool for use in the corpus cavernosal lumen in patients with erectile dysfunction

Study Type – Diagnostic (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? In visualizing the artery in patients with ED, digital subtraction angiography, CT angiography and color Doppler ultrasonography has been performed. There were difficulties with the previous methods in visualizing the stenotic lesion, or parts beyond the obstruction of the artery. Virtual cavernoscopy can visualize an artery independently of blood flow. We therefore believe that this new imaging technology will contribute to better ED practice.

OBJECTIVE

? To evaluate virtual cavernoscopy as a diagnostic tool in erectile dysfunction.

PATIENTS AND METHODS

? Forty patients who visited our hospital for investigation of erectile dysfunction underwent cavernosography using three‐dimensional (3D)‐computed tomography (CT). ? Virtual cavernoscopic images were reconstructed from 3D‐CT data.

RESULTS

? Virtual cavernoscopic images were obtained from all patients. ? Virtual cavernoscopy visualized the corpus cavernosal lumen surrounded by the tunica albuginea, the septum of the cavernosum, the outlets of the veins, and cavernous arteries. ? The visualization of each structure depended on the window level (WL). At WL 400, the virtual cavernoscopy visualized only a fibrous structure. At this WL, the internal view of the corpus cavernosum was expressed as a hollow space. At WL 1600, the virtual cavernoscopy visualized the cavernous artery as a filling defect. ? Out of 80 lumens in the 40 subjects, arteries in 14 lumens were detected by both virtual cavernoscopy and CT angiography, while arteries in 50 lumens were detected only by virtual cavernoscopy. Arteries in two lumens could not be visualized by either method and those in 14 lumens were visualized only by CT angiography.

CONCLUSION

? In visualizing the artery, conventional imaging techniques depend on blood flow, whereas using virtual cavernoscopy an artery can be visualized independently of blood flow. Virtual cavernoscopy is unique in this regard and we therefore believe that this new imaging technology will contribute to better ED practice.     

Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction

Phenotypic modulation from a contractile to a proliferative state within vascular smooth muscle cells has a critical role in the pathogenesis of a variety of cardiovascular diseases. To investigate the characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction, a group of Sprague-Dawley rats (n=30) were induced by intraperitoneal injection of streptozotocin (60?mg?kg(-1)) and screened by subcutaneous injection of apomorphine (100?μg?kg(-1)) for the measurement and comparison of the penile erections, and then three different groups were defined. Primary corpus cavernosum smooth muscle cells were cultured and passaged. The cavernous tissue segments were subjected to quantitative real-time polymerase chain reaction to determine the expressions of smooth muscle α-actin (SMA), SM myosin heavy chain (SMMHC), smoothelin, calponin and myocardin. Cell contractility in vitro and western blot analysis of SMA and SMMHC in the cavernous tissues and cells were determined. Compared with the control group (n=8) and the diabetes mellitus group (n=5), the expressions of SMA, calponin, SMMHC, smoothelin and myocardin mRNA were decreased in the cavernous tissues in rats of the diabetic erectile dysfunction group (n=15; P=0.001 and 0.02, P=0.014 and 0.012, both P<0.001, P=0.005 and <0.001, P=0.003 and 0.035, respectively). The levels of SMA and SMMHC proteins showed a significant decrease in cavernous tissues and cultured cells in rats of the diabetic erectile dysfunction group. Cells of the diabetic erectile dysfunction group exhibited significantly less contractility compared with those of other groups (P<0.001). Corpus cavernosum SM cell possesses the ability to modulate the phenotype under hyperglycemic conditions, which could have a key role in the pathogenesis of diabetic erectile dysfunction.     

Revascularization of corpus cavernosum for erectile failure.

Revascularization of the penis for erectile disability was performed in 10 patients in whom arterial obstruction had been documented. Inferior epigastric artery anastomosis to the corpus cavernosum was not successful, although bypass grafts from the femoral artery to the corpus cavernosum have helped restore potency in 4 of 6 patients. Complications included embolus to the leg, postoperative hemorrhage, and three small hematomas. This procedure can be considered a clinical experiment and would call for more study to assess its ultimate value.     

Human neural crest stem cells transplanted in rat penile corpus cavernosum to repair erectile dysfunction

OBJECTIVE

To investigate the feasibility of applying neural crest stem cells (NCSCs), with multipotent capacity, to repair injury in the penile cavernosum, the HNC10.K10 (K10) immortalized NCSC line was transplanted into the penile cavernosum of adult rats, as one of the causes of erectile dysfunction is damaged penile cavernous smooth muscle cells and sinus endothelial cells.

MATERIALS AND METHODS

The K10 human NCSC line was generated via transfection of primary cultured NCSC with a retroviral vector encoding v‐myc. K10 NCSCs were transplanted into the cavernosum of adult rats. The expression of cell type‐specific markers for endothelial cells (CD31 and von Willebrand factor), and specific markers for smooth muscle cells (smooth muscle cell actin, calponin, and desmin) was determined immunohistochemically in the penile cavernosum of rats 2 weeks after transplantation.

RESULTS

In the rat cavernosum, transplanted K10 NCSCs identified by human nuclear antigen labelling expressed cell type‐specific markers for endothelial cells (CD31 and von Willebrand factor), and specific markers for smooth muscle cells (smooth muscle cell actin, calponin, and desmin) 2 weeks after transplantation. Human NCSCs transplanted into the rat penile corpus cavernosum differentiated into endothelial cells or smooth muscle cells, as shown by their expression of cell type‐specific markers for the cell types.

CONCLUSION

It appears that NCSCs are an ideal cell source for reconstructing endothelial and smooth muscle cells in the corpus cavernosum in cell therapy for patients with erectile dysfunction.     

Long-term results of corpus cavernosum auto-injection therapy in treatment of patients with chronic erectile dysfunction]

From May 1985 to July 1989, 143 patients suffering from chronic erectile dysfunction (21-70 years old) underwent constant corpus cavernosum auto-injection therapy (CCAT) with papaverine alone (1257 injections) or with a standardized papaverine-phentolamine mixture (11035 injections). On the basis of these 12,292 protocol auto-injections and over 4 years' experience with intracavernosal auto-injection therapy we conclude: CCAT, especially with the papaverine-phentolamine mixture, constitutes an effective therapy (full rigidity in 95.9%) with tolerable side-effects for chronic erectile dysfunction when preceded by careful patient selection and thorough multidisciplinary evaluation, especially in the case of arterial and/or neurogenic aetiology of the erectile dysfunction; in addition, the contraindications must be strictly observed, the treatment and technique fully explained, and a regular system instituted. CCAT is generally well accepted by the patients and their partners (100%/98.3%) and has distinct positive effects on self-esteem (77.8%), performance anxiety (84.4%) and partnership (79.5%). The most serious side-effect was prolonged erection (25 out of 12,292 injections). In 3 patients reversible fibrotic changes near the tunica albuginea were observed.     

糖尿病性勃起功能障碍大鼠中低睾酮水平对阴茎海绵体平滑肌的影响

目的 观察糖尿病性勃起功能障碍(DMED)大鼠的睾酮水平变化对其阴茎海绵体平滑肌组织和超微结构的影响.方法 将3个月龄雄性Wistar大鼠20只随机等分为两组:正常对照组和DMED组,行放射免疫法测定其血清睾酮浓度和masson染色观察阴茎海绵体平滑肌(CCSM)密度以及通过透射电镜观察海绵体平滑肌细胞的超微结构.结果 DMED组大鼠的血清睾酮水平(17.445 ±2.540) nmol/L较正常组(338.457±63.802) nmol/L明显下降(P＜0.01);同时DMED组大鼠CCSM密度(5.640±0.597)％较正常对照组(19.890±1.957)％亦明显减少(P＜0.01),透射电镜下还观察到DMED组大鼠阴茎CSMC的核浆比增大,高尔基复合体明显肥大以及线粒体水肿.结论 睾酮水平下降可能导致DMED大鼠阴茎海绵体平滑肌发生病理变化.     

Histopathological changes and nitric oxide synthase activity in corpus cavernosum from rats with neurogenic erectile dysfunction

OBJECTIVE: To investigate changes in histology and nitric oxide synthase (NOS) activity in cavernosal tissues from rats with neurogenic erectile dysfunction induced experimentally. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided equally into three groups and underwent a sham operation (control, group 1), unilateral (group 2) or bilateral (group 3) cavernosal nerve resection. Three months later they were killed and the cavernosal tissues analysed histologically by light and transmission electron microscopy, with NOS activity detected using an NADPH-diaphorase staining technique. RESULTS: On light and electron microscopy, while penile nerves and cavernosal smooth muscle cells had a normal morphological appearance in the eight control rats, there were degenerative changes of the myelinated penile nerves and axonal fibrosis in groups 2 and 3. However, these changes were not significant. Using NADPH-diaphorase staining, NOS activity was detected in all three groups in endothelial cells and cavernosal structures. However, the staining was more intense in endothelial cells and cavernosal muscles of rats in group 2 than in the other groups. CONCLUSION: NOS activity was increased in the cavernosal tissue after cavernosal denervation, but the pharmacological action of nitric oxide may be impaired.