Computerized analysis of smooth muscle fibers in potent and impotent patients

Reduction or dysfunction of the intracavernous smooth muscle fibers can provoke impotence. Computerized digital image analysis of corpus cavernosum biopsies was performed in potent and impotent patients to quantify the percentage of smooth muscle fibers. In 5 normal patients the smooth muscle area represented 40 to 52% of the specimen, in 20 patients with cavernous dysfunction it was 10 to 36% and in 10 patients with arterial disease it was 13 to 25%. This method appears to be important to understand better certain mechanisms of impotence and to approach the potential treatment.     

Basic and clinical research of impotence--its present situation and problems involved

From detailed investigation of the vascular structure of the penis, it has been proposed that there exists a valvular structure, consisting of smooth muscle, located at a point immediately before the helicine artery, bifurcated from the deep artery, opens to the cavernous sinuses, an area where autonomic nerves are densely distributed, participating in opening and closing the valve. On the other hand, there is said to be no valvular structure in the vein outflowing from the cavernous sinuses, and blood flows into the dorsal penile vein by penetrating the albuginea obliquely or vertically after running parallel in the region immediately below the albuginea. It is considered that, when the valve of the helicine artery opens, blood flows into the cavernous sinuses, expanding them, and as a result the outflowing vein is compressed between the sinuses and the albuginea, or the albuginea itself, acting like a valve and therefore assuming an important function in maintaining erection by disturbing the reflux of blood flow. It is also presumed that the contracting of ishiocavernous muscle plays a part in developing the rigidity of the penis. It is considered, moreover, that the trabecula of the cavernous body consisting of smooth muscle also plays a part in the promotion and disappearance of erection. It is very important to run functional tests of erection when diagnosing impotence, and today many tests are available for differential diagnosis; including papaverine test, dynamic cavernosometry and cavernosography. As for therapy, treatments involving vasoactive agent infusion, such as papaverine or prostaglandin E1 into the cavernous body, have become common. For cases with venous impotence, ligation of the penile deep vein and crus of the penile cavernous body have come to be attempted. Furthermore, revascularization of penile artery can be performed to treat arterial impotence. For cases in whom these methods are not effective, implantation of various penile prostheses into the penis has been shown to be successful.     

Penile venous drainage in erectile dysfunction. Anatomical, radiological and functional considerations

To elucidate further the penile venous anatomy and its role in the haemodynamics of erection, we performed pharmacological cavernometry and cavernography in 95 patients with venogenic impotence and in 12 patients with psychogenic impotence. The findings were correlated with those of dissection in 10 adult male cadavers. Cavernography confirmed that the main venous drainage of the corpora cavernosa is via the cavernous veins, with additional drainage through the crural, circumflex and deep dorsal veins and demonstrated that, in patients with venogenic impotence, the cavernous veins are the common site of leakage. Cavernometry provided valuable parameters for the quantification of the degree of venous leakage. Detailed knowledge of the penile venous system and cavernometry and cavernography are essential for the proper diagnosis and treatment of patients with venogenic impotence.     

Norepinephrine involvement in response to intracorporeal injection of papaverine in psychogenic impotence.

The levels of catecholamines in penile blood during a papaverine test were measured to investigate whether the secretion of endogenous catecholamines is involved in response to intracorporeal papaverine injection. The level of norepinephrine was higher in patients with psychogenic impotence than in the normal controls and patients with vasculogenic impotence (p less than 0.01), and it was significantly higher in negative responders than in positive responders in the psychogenic impotence group (p less than 0.001). There was no significant difference in the level of epinephrine among the groups. The false negative response to the papaverine test in psychogenically impotent men is believed to be derived from secretion of cavernous norepinephrine, which overwhelms the action of cavernous smooth muscle relaxation by papaverine.     

Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients

A functional study was done to examine a possible role of calcitonin-gene-related peptide in human penile erection and its possible therapeutic applications for patients with erectile dysfunction. In the determination of an effective dosage, 5 ng. (2 patients), 50 ng. (2 patients), 500 ng. (4 patients), 5 micrograms (4 patients) and 25 micrograms (7 patients) were injected intracavernously, and pulse and blood pressure were monitored. Arterial inflow was measured by Doppler sonography, smooth muscle relaxation was determined by the analysis of cavernous electrical activity and cavernous outflow occlusion was recorded by cavernosometry. In 12 patients the erectile response of prostaglandin E1 was compared to the response of an equal (6 patients) or decreased dose of prostaglandin E1 combined with an equal weight of calcitonin-gene-related peptide. In 14 patients the erectile response to the combination of calcitonin-gene-related peptide and prostaglandin E1 was compared to the response of prostaglandin E1 alone, and with a combination of 15 mg./ml. papaverine and 0.5 mg./ml. phentolamine. Calcitonin-gene-related peptide induced an increase in the penile arterial inflow, cavernous smooth muscle relaxation and cavernous outflow occlusion. Histochemical results indicated nerve fibers positive for calcitonin-gene-related peptide within the cavernous bodies. A dose-dependent erectile response to calcitonin-gene-related peptide was observed at doses of 500 ng. to 25 micrograms. Systemic side effects were first observed at a dose of 25 micrograms in 2 of 7 patients. The combination of calcitonin-gene-related peptide and prostaglandin E1 was more effective in inducing a full erection than either prostaglandin E1 alone or the combination of papaverine and phentolamine. Pain was reported in 4% of the patients who received the combination of calcitonin-gene-related peptide and prostaglandin E1, whereas 42% of those who received prostaglandin E1 alone reported pain. Our results suggest that calcitonin-gene-related peptide may be a possible neurotransmitter for penile erection. A combination of calcitonin-gene-related peptide and prostaglandin E1 seems to be an effective alternative combination in the treatment of impotence.     

高血压大鼠海绵体平滑肌细胞间连接的变化

目的:比较自发性高血压大鼠(SHR)和正常血压大鼠阴茎海绵体平滑肌细胞间连接改变及与阴茎勃起功能的关系。方法:注射阿朴吗啡(APO)观察14周龄SHR(SHR组,n=5)、W istar-Kyoto大鼠(WKY组,n=5)阴茎勃起情况,用透射电镜观察其阴茎海绵体平滑肌细胞间连接超微结构,RT-PCR测定海绵体平滑肌细胞Connexin 43的mRNA表达,免疫组化观察Connexin 43蛋白表达。结果:SHR组大鼠阴茎勃起次数明显低于WKY组(P<0.05),电镜发现SHR组大鼠阴茎海绵体平滑肌细胞间大量胶原纤维增生,Connexin 43蛋白及其mRNA表达较WKY组显著降低(P<0.05)。结论:高血压影响阴茎勃起功能,阴茎海绵体平滑肌细胞间连接的病理改变可能是高血压性勃起功能障碍的发病机制之一。     

Diagnosis of a venous fistula as a cause of erection disorders. Experimental principles and practical conclusions

An experimental study was done in ten dogs and eight monkeys to evaluate the accuracy of dynamic and pharmacologic cavernosometry and cavernosography in the diagnosis of venogenic impotence. Our findings show that erection induced by saline perfusion comes about because the penile venous outflow capacity is exceeded. Thus, the cavernous occlusive mechanisms are not activated. Cavernosography in induced erection always demonstrated the entire cavernous venous system. However, cavernosometry after pharmacologic cavernous smooth muscle relaxation provides useful diagnostic information. Similarly, cavernosography after pharmacologic cavernous smooth muscle relaxation proved to be useful for the identification of abnormally draining veins.     

Content and distribution of vasoactive intestinal polypeptide (VIP) in cavernous tissue of human penis

Penile erection is controlled by a valvular structure in the helicine artery in humans. The opening and closing of this valve are believed to be regulated by the autonomic nervous system, especially through the release of vasoactive intestinal polypeptide (VIP). We determined the content of VIP in cavernous tissue in 18 impotent patients and in 5 normal controls by radioimmunoassay, and we examined the distribution of VIP-ergic nerve fibers in cavernous tissue by an immunohistochemical method. As a result, it was found that the lower penile VIP content was more frequent among patients with organic impotence than among the controls. Furthermore, VIP-ergic nerve fibers were seen to be diffusely and loosely distributed in a large number of organic impotence patients. These findings suggest that organic impotence in some patients may be due to decreases in the VIP content and in VIP-ergic nerve fibers.     

Evaluation of the role of corpus cavernosum electromyography as a noninvasive diagnostic tool in male erectile dysfunction

Corpus cavernosum electromyography (EMG) and its evolution: single potential analysis of cavernous electrical activity (SPACE) seem to be promising diagnostic methods in the evaluation of erectile dysfunction and smooth muscle integrity [4]. Our study concentrates on the role of EMG in the evaluation of corpus cavernosum smooth muscles, using it as a noninvasive technique for demonstrating autonomic erectile dysfunction through their influence on recording SPACE and consequent proper selection of patients for different therapeutic modalities. A total of 80 male patients were examined for the feasibility of transcutaneous registration of cavernous electrical activity with a 2-channel electrophysiological unit (Evamatic 2000, Dantec) with two surface electrodes bilaterally placed on the penile shaft. Ten patients had normal erectile function, but complained of other urological symptoms. They served as the controls for normal electrical activity. Fifty patients with organic impotence of nonvascular (neurogenic) or vascular (venogenic, arteriogenic) aetiologies were subjected to EMG in both the flaccid and the erect state. On the basis of the EMG patterns the patients were divided into the following groups: 34 patients having normal tracing in both the flaccid and the erect state, and 21 patients showing abnormal patterns of waves with evidence of autonomic neurogenic dysfunction and incomplete smooth muscle relaxation. Of the latter 4 had long-standing diabetes mellitus and 4 had spinal injuries.     

Congenital defect in sinusoidal smooth muscles: a cause of organic impotence.

We report 2 cases of primary impotence due to a congenital defect in the compliance of the sinusoidal spaces secondary to fibrosis and atrophy of the smooth muscles. Both patients were young adults at presentation. Diagnosis of this rare entity was achieved by penile Doppler ultrasound and cavernosometry/cavernosography of the cavernous bodies. Both patients underwent placement of a penile prosthesis, during which biopsy samples of the cavernous tissue were obtained, and diagnosis was confirmed by light and electron microscopy.     

Autonomic nerve involvement and venous leakage in diabetic men with impotence

OBJECTIVE: To determine the neurophysiological and vascular factors in diabetic impotence, particularly the role of autonomic neuropathy on venous leakage and erectile impotence. PATIENTS AND METHODS: Thirty-four diabetic men with impotence were investigated using various neurophysiological and radiological methods. The results were compared with those from patients with idiopathic penile venous leakage for autonomic neuropathy, especially for spontaneous cavernosal activity (SCA). RESULTS: Of the neurophysiological tests, the SCA was most frequently abnormal, with the loss of normal periodic oscillations. Penile venous leakage, either alone or with arterial insufficiency, was the most frequent vascular problem (67%) in patients with diabetic impotence, in whom the SCA was absent in most (83%). Conversely, the SCA was normal in all impotent patients with idiopathic venous leakage. CONCLUSION: Venous leakage in diabetic patients is probably produced by autonomic dysfunction of the penile vascular innervation or degeneration of penile smooth muscles, because the SCA was absent more often in these patients.     

Arteriographically determined occlusive disease within the hypogastric-cavernous bed in impotent patients following blunt perineal and pelvic trauma

To determine the presence, location and pattern of arterial occlusive disease within the hypogastric-cavernous arterial bed in impotent men following blunt perineal and pelvic trauma, we reviewed the selective internal pudendal arteriograms of 20 patients with a history of blunt perineal and 7 with blunt pelvic trauma who had immediate development of impotence. Arteriographic studies of 104 other impotent patients also were reviewed and compared. Patients with persistent impotence immediately after blunt pelvic and perineal trauma had significantly different patterns of arteriographically demonstrated occlusive disease within the distal hypogastric-cavernous arterial bed consistent with the site of the traumatic injury. Those who sustained blunt pelvic trauma and complained of immediate impotence revealed arterial occlusive lesions mainly in the internal pudendal, common penile, cavernous and dorsal arteries. The incidence of arterial lesions in the distal internal pudendal or common penile artery was significantly higher (p less than 0.01) in patients with blunt pelvic trauma (92%) than in those with blunt perineal trauma (35%). Patients who sustained blunt perineal trauma and complained of immediate impotence demonstrated a more focal pattern of pathological arterial occlusion primarily in the cavernous and dorsal arteries. The incidence of a solitary arterial lesion in the cavernous artery without proximal disease was significantly higher (p less than 0.05) in patients with blunt perineal trauma (48%) than in those with blunt pelvic trauma (8%). It is hypothesized that blunt trauma without immediate impotence may be a potential risk factor for later development of arterial vasculogenic impotence, and that unrecognized or seemingly innocuous trauma may be a factor in cases of idiopathic impotence. Patients without trauma and with vascular risk factors have a more diffuse pattern of arteriographically demonstrated arterial lesions.     

CAVERNOUS ARTERIAL AND ARTERIOLAR CIRCULATION IN PATIENTS WITH ERECTILE DYSFUNCTION: A POWER DOPPLER STUDY

Purpose

We assessed the morphodynamic features of cavernous arteries and helicine arterioles by power Doppler sonography in vasculogenic and nonvasculogenic impotent men.

Materials and Methods

A total of 40 impotent patients with and without definite vascular risk factors were studied by penile power Doppler sonography. The test was performed during penile flaccidity, after intracavernous injection of 20 mcg. alprostadil and after subsequent genital and audiovisual sexual stimulation. A second injection and stimulation were given if the erectile response observed after the initial injection was less than the maximum erection seen during sexual activity. Morphodynamic parameters evaluated by power Doppler imaging included vessel course, shape, wall thickness and pulsatility, peak systolic velocity, end diastolic velocity, acceleration time and resistance index.

Results

In the nonvasculogenic group all patients who achieved rigid erection showed normal cavernosal artery and helicine arteriole inflow. In these cases the arteriolar picture was characterized by the presence of 3 orders of distal ramifications originating from the cavernous arteries with an acute angle, systolic diastolic flow during penile tumescence and systolic flow alone at full rigidity. In the vasculogenic group patients with normal cavernous artery inflow showed an arteriolar tree that was pathological in 50% and was characterized by a reduced number of ramifications originating perpendicularly from the cavernous arteries and irregular caliber (arteriolar impotence). In the same group patients with reduced cavernous artery inflow also showed normal or pathological arteriolar components (pre-penile arterial impotence and diffused penile arterial impotence).

Conclusions

Power Doppler sonography allows a precise study of the morphodynamics of the cavernous arteries and helicine arterioles. Our preliminary data suggest that the intracavernous arteriolar component may have a significant role in the genesis of some forms of vasculogenic impotence.     

糖尿病性阴茎勃起功能障碍大鼠模型海绵体超微结构的研究

目的　探讨糖尿病（ＤＭ） 性阴茎勃起功能障碍（ＥＤ） 的发病机理。　方法　ＳＤ 大鼠注射链脲佐菌素制造ＤＭ 动物模型后,注射阿朴吗啡观察６ 周、８ 周及１２ 周大鼠阴茎勃起情况,筛选ＤＭ 性ＥＤ 大鼠模型,观察其阴茎海绵体组织超微结构的改变。　结果　ＤＭ 性ＥＤ 大鼠模型阴茎海绵体内皮细胞及平滑肌细胞超微结构均有明显的病理改变：线粒体退变、内质网扩张,糖原颗粒、吞饮小泡及微丝减少。此外,还可见大量间质组织增生及微血管腔闭塞。随ＤＭ 病程不同,其改变程度不同,８ 周时以内皮细胞损害为明显,１２ 周时以平滑肌细胞损害为明显。　结论　ＤＭ 严重影响阴茎勃起功能,海绵体组织超微结构的病理改变可能是ＤＭ 性ＥＤ 发病机理之一。     

Correlation between penile angiography and duplex scanning of cavernous arteries in impotent men

During the diagnostic evaluation of patients with vasculogenic impotence duplex scanning has been proposed as a reliable noninvasive method to evaluate the cavernous arteries. However, the sensitivity and specificity of this test have never been elucidated. To provide insight into the clinical value of this test 25 men who presented with impotence and failed to respond to 60 mg. intracavernous papaverine were evaluated with duplex scanning and the results of this modality were compared to penile angiography. The cavernous arteries were considered normal by duplex scanning if the artery demonstrated either a 60% or greater increase in diameter and/or a peak flow velocity of greater than 25 cm. per second 5 minutes after papaverine injection. Penile angiography was considered normal if both cavernous arteries were visualized and appeared to be normal radiographically (after intracorporeal papaverine). In the 25 patients studied there was no significant difference in peak flow velocity between patients with normal or abnormal cavernous arteries by angiography. In addition, arterial dilatation (more than 60%) after papaverine injection did not correlate with the results of the angiogram. These data demonstrate that duplex scanning of the cavernous arteries does not correlate well with what is observed by penile angiography in a selected population of men with vasculogenic erectile dysfunction. Since penile angiography itself has limitations in the evaluation of the penile arteries, the reliability of duplex scanning to identify cavernous artery dysfunction needs additional confirmation.     

Hydraulic penis prosthesis in fibrosis of the cavernous body. The alloplastic tunica albuginea

Fibrosis of the cavernous bodies is a rare but serious condition resulting in erectile impotence. When the fibrosis is extensive a simple penile prosthesis sometimes cannot be implanted. In addition, perforation of the tunica albuginea is not uncommon in damaged cavernous bodies, and this will compromise a reimplantation. In such cases, the use of an alloplastic vascular prosthesis permits replacement of lost cavernous wall tissue and insertion of an inflatable penile implant. We used this technique in 10 patients with severely damaged cavernous bodies. In 7 of them, surgery was successful and enabled satisfactory intercourse. This type of surgery, however, should be reserved for selected cases of penile prosthetic surgery.     

Fibrosis of corpus cavernosum in animals following cavernous nerve ablation

Aim: To investigate alterations of smooth muscle celis and collagen fibers in corpus cavernosum following cavernous neurectomy and its relation to the expression of transforming growth factor-β1 (TGF-β1). Methods: Ten adult male SD rats (neurectomy group) were subject to a bilateral cavernous nerve (CN) resection aseptically under an operating microscope, with 6 sham-operated rats as the control. Fifteen weeks after the operation, the penile speci mens were collected and prepared for quantitative-analyzing of ratio of smooth muscle to collagen fibers in corpus cavernosum with confocal microscopy, and for detecting the expression of TGF-β1 by RT-PCR and western-blot. Resulte: Smooth muscle celis that show red color after fluorescent-labeling with tetramethylrhodamine isothiocyanate phalloidin and collagen fibers that produce green autofluorescence after paraformaldehyde fixation were clearly iden tified     

Ultrastructural analysis of human penile corpus cavernosum Its significance in tumescence and detumescence

The erectile tissue from 15 normal and impotent male patients was studied by electron microscopy to determine if any ultrastructural features could contribute to the basic understanding of the physiology of penile erection and detumescence. It was found that the endothelium lining the cavernous lacunae contained both contractile elements and Weibel-Palade bodies which have a possible role in vasoconstriction. Within the trabeculae of the cavernous body there was an abundance of elastin as well as oxytalan and elaunin fibers around bundles of smooth muscle. With these elements affording an anchorage system for contraction of smooth muscles within the trabeculae, an alternate contraction of smooth muscles and endothelium could account for the erectile and detumescent states.     

血管性阳痿阴茎血流动力学研究及微循环检测

目的：研究血管性阳痿病人阴茎头微循环及其血流动力学特点,并对二者相关性进行比较。　方法：分别检测１７ 例血管性阳痿病人和１１ 名健康志愿者的阴茎头微循环,同时用超声多普勒研究其血流动力学指标,并分析二者间的相关关系。　结果：血管性阳痿病人与健康志愿者阴茎头微血管密度为（２７．１±５．２）条／ｍ ｍ ２ ｖｓ （４７．８±６．２）条／ｍ ｍ ２ （ Ｐ＜ ０．０１）,异常微血管百分率为（３２．１±３．４）％ ｖｓ （１２．８±１．３）％ （ Ｐ＜ ０．０１）及阴茎 臂指数（ Ｐ Ｂ Ｉ）值与对照组相比差异显著;阴茎血流动力学指标中 Ｐ Ｂ Ｉ值与微循环检测的两项指标均显著相关;阴茎血流动力学指标中阴茎各动脉的血流速度与微循环指标相关不明显。　结论：血管性阳痿病人的阴茎头微循环有器质性改变,这种改变与阴茎血流动力学之间相关不明显,阴茎血流动力学指标的检测易受各种因素的干扰。     

A possible role for calcitonin-gene-related peptide in the regulation of the smooth muscle tone of the bladder and penis

We investigated the effect of calcitonin-gene-related peptide (CGRP) on bladder contractions and penile erection in 12 dogs. In a system in which the arteries were tied bilaterally to ensure delivery of high drug levels to the bladder, arterial injections of CGRP significantly reduced the peak intravesical pressure of bladder contractions induced by pelvic nerve stimulation or arterial injection of carbachol. When given intravenously, CGRP had no effect on bladder contractions consequent to neural stimulation. Intravesical instillation of CGRP, however, reduced the bladder contractions significantly. Histologic staining showed CGRP-immunoreactive nerve fibers within the smooth muscle layers of the bladder wall. Intracavernous CGRP increased cavernous arterial flow and induced cavernous smooth muscle relaxation and venous outflow occlusion. Muscarinic blockade had no effect on the canine intracavernous pressure response to intracavernous injection of CGRP. Histologic staining for CGRP-immunoreactivity showed nerve-fiber-like staining within the cavernous arterial wall, the nerves running near the cavernous arteries, and the cavernous smooth muscles. Our results suggest a possible role for CGRP in the regulation of the smooth muscle tone of the bladder and penis.