Herb formula enhances treatment of impotent patients after penile venous stripping: a randomised clinical trials.

Herbs have been regarded as aphrodisiacs in treating impotence for many centuries despite little true scientific evidence. Our latest refined penile venous stripping (PVS) technique is effective in treating impotence, although this procedure remains controversial. A synergic effect of PVS and oral herbs was confirmed in our practice but lacked rigorous scientific proof. The objective of this report was to review our experience with this combination. From August 2010 to May 2014, 263 males underwent PVS. Among these, 67 unsatisfied men chose additional salvage therapy and were randomly assigned to oral herbs (n = 35) or placebo treatment (n = 32) which replaced herb eventually. All were evaluated with the international index of erectile function (IIEF-5) scoring and our dual pharmaco-cavernosography. The pre-op IIEF-5 score for the herb group was 9.7 ± 3.7, post-operative 13.9 ± 3.3 and post-herb 19.6 ± 3.4, while the control group scores were as follows: pre-op 9.3 ± 4.1, post-op 14.5 ± 3.6, post-placebo 15.1 ± 3.5 and post-herb 19.9 ± 3.2. Although there was no significant difference between the two groups pre-operatively, post-operatively and post-herb, a statistically significant difference was found post-salvage therapy (19.6 ± 3.4 versus 15.1 ± 3.6, P < 0.001). It appears that the combination of oral herbs and PVS treatment provides an enhanced outcome to impotent patients refractory to medicine and unsatisfied with PVS monotherapy alone.

Formulas for determining the dimensions of venous graft required for penile curvature correction.

To evaluate the quantity of penile veins for use as patch material for the treatment of penile curvature, we devised two formulas: from the calculus of applied civil engineering and a diagram from the goniometry of the cadavers' penises, respectively, and the techniques for their application. From March 1995 to July 2003, a total of 65 consecutive patients with penile curvature - 41 men with Peyronie's deformity and 24 with congenital penile deviations - underwent grafting with autologous deep dorsal veins with or without cavernosal veins as patch material. The patched veins required were calculated from the formula (pi)r(2)theta/45 degrees , which is derived from calculus. The tunical incision sector was meticulously performed in accordance with our diagram which is interpolated from seven male cadavers via goniometry and consequently the length of patched veins required was 2 (pi)r(theta)(')/theta. The corporotomy defect was fashioned with the detubularized veins after they were adequately prepared and spliced. In these patients, the average available area of the veins was 4.9 x 2.2 cm(2) (range, 4.5 x 1.8 to 5.6 x 2.4), which seemed adequate in all cases for patching, although 11 of them required two patches. Overall, 21 patients required a modified Nesbit's procedure on the contralateral/ipsilateral tunica to attain a satisfactory penile shape. Because of its anatomical vicinity and its availability as material, the deep dorsal vein associated with the cavernosal vein may play an indispensable role in grafting even with local anaesthesia on an outpatient basis.

The anatomy of the tunica albuginea in the normal penis and Peyronie's disease.

PURPOSE: We studied the fine architecture of the tunica albuginea of the penis. MATERIALS AND METHODS: The study included 6 human male cadavers and 10 surgical patients (5 with Peyronie's disease and 5 with normal penile anatomy). RESULTS: The tunica albuginea of the corpora cavernosa is a bi-layered structure with multiple sub layers. Inner layer bundles support and contain the cavernous tissue and are oriented circularly. Radiating from this layer are intracavernous pillars acting as struts, which augment the septum and provide essential support to the erectile tissue. Outer layer bundles are oriented longitudinally. These fibers extend from the glans penis to the proximal crura, where they insert into the inferior pubic ramus. There are no outer layer fibers between the 5 and 7 o'clock positions. Elastic fibers normally form an irregularly latticed network on which collagen fibers rest. In Peyronie's disease the well ordered appearance of the collagen layers is lost: excessive deposits of collagen, disordered elastic fibers and fibrin are found within the region of the plaque. CONCLUSIONS: The normal 3-dimensional structure of the tunica affords great flexibility, rigidity and tissue strength to the penis, which are lost consequent to structural changes in Peyronie's disease.

Out-patient surgery for the correction of penile curvature.

OBJECTIVE: To evaluate an outpatient anaesthetic and surgical procedure for the correction of curvature of the penis. PATIENTS AND METHODS: From February 1993 to December 1995, 128 patients (mean age 31 years, range 14-67) with penile curvature (120 with congenital curvature and eight with penile deformity from Peyronie's disease) were treated as out-patients at our institution using a proximal dorsal nerve block and ventral infiltration of the penis as the method of anaesthesia. The degree of deformity, pain and sexual activity were assessed before and after surgery and all patients were followed post-operatively using a questionnaire to determine the outcome and their satisfaction. RESULTS: All the patients were able to leave the hospital shortly after surgery. The follow-up period ranged from 4 to 35 months (mean 17.3); 112 patients (87.5%) reported a satisfactory cosmetic and functional result, while the other 16 patients reported an improvement but had inadequate correction. There were no significant short- or long-term complications; three patients with diabetes developed a hard lump over the operated tunica. CONCLUSIONS: This unique operative method provided excellent correction of the deformities, was safe, cost-efficient and durable and could be performed as an out-patient procedure.

Structural alterations in the tunica albuginea of the penis: impact of Peyronie's disease, ageing and impotence.

OBJECTIVE: To investigate whether changes in the structure of the tunica albuginea influence the development of erectile dysfunction. PATIENTS AND METHODS: Biopsy specimens taken from the tunica of 64 patients (both potent and impotent) with and without Peyronie's disease were evaluated. Tissue samples were stained and examined under light and electron microscopy, and the concentration of elastic fibres present in each was measured using computerized image analysis. RESULTS: The concentration of elastic fibres was lower in impotent than in potent patients (P = 0.0365) and was also significantly less in patients with Peyronie's disease. Furthermore, the concentration of elastic fibres decreased with age. Electron and light microscopy revealed the presence of distinct alterations in the tunica albuginea in impotent patients and patients with Peyronie's disease that might interfere with function. CONCLUSION: The decrease in elastic fibre concentration and changes in microscopic features may contribute to erectile dysfunction by impairing the veno-occlusive function of the tunica albuginea.

Chronic penile denervation in the rat: effect on cavernous tissue morphology and function.

We evaluated the effects of chronic penile denervation on cavernous tissue morphology and function in 36 Sprague-Dawley rats. At age seven weeks, 18 animals underwent bilateral cavernous nerve neurectomy: 18 animals underwent sham operation as a control. A functional, biochemical and morphological assessment of the rats' penises was performed at 4 months. In denervated rats, intracavernous pressure failed to rise with electrostimulation of the pelvic plexus. However, a normal rise in pressure was found with direct intracavernous injection of sodium nitroprusside and papaverine. Sodium dodecylsulfate polyacrylamide (SDS) gel electrophoresis of the penile homogenate showed subtle differences between denervated and control animals. Based upon the histological findings there was no difference in staining of the cavernous tissue for acetylcholinesterase- and catecholamine-positive nerve fibers between experimental and control animals, since the innervation density was not quantified and the number of fibers was not counted. We conclude that chronic cavernous nerve neurectomy does not cause significant morphological or functional changes to the penile erectile tissue of rats.

The effect of intracavernous injection of potassium channel openers in monkeys and dogs.

Cavernous smooth muscle relaxation is effected through a complex biochemical pathway; therefore, a defect in any step of this pathway may result in erectile dysfunction. Administration of pharmacologic agents which cause relaxation of the cavernous smooth muscle through a different mechanism may serve as an effective therapeutic alternative for impotent patients. To test this hypothesis two potassium channel openers, pinacidil and cromakalim, were used to initiate and maintain cavernous smooth muscle relaxation. The drugs were given as intracavernous injections in two animal models. In 10 dogs pinacidil and cromakalim produced full erection. With pinacidil (10(-2) M), the mean intracavernous pressure increased from a baseline pressure of 32.6 +/- 3.43 cm H2O to a peak intracavernous pressure of 131.8 +/- 12.01 cm H2O, and remained elevated for a period of 17.8 +/- 9.4 min. With cromakalim (10(-2) M) intracavernous pressure rose from a baseline pressure of 32 +/- 2.55 cm H2O to a peak intracavernous pressure of 140 +/- 3.39 cm H2O, for a period of 19.4 +/- 0.89 min. Additionally, in 5 primates injected with cromakalim (10(-2) M) intracavernous pressure rose from 24 +/- 3.81 to 131.2 +/- 7.56 cm H2O, for 27.0 +/- 4.79 min. It is concluded that both pinacidil and cromakalim can initiate and maintain erection in dogs and that cromakalim produces a similar erectile response in monkeys. Further study of the local and systemic effects of chronic injection is needed to determine whether this class of pharmacologic agents can provide therapy for impotent patients.

Sodium nitroprusside: physiologic effects as a nitric oxide donor in three species.

Recent in vitro and in vivo studies have suggested that nitric oxide may be the neurotransmitter responsible for cavernous smooth muscle relaxation and penile erection. Sodium nitroprusside, after combining with different kinds of thiols in the cellular cytoplasm, can effect nitric oxide release. We undertook this study to determine the physiologic response to sodium nitroprusside injection when used to induce and maintain penile erection in three species. Sodium nitroprusside was injected in increasing concentrations into the cavernous tissue of rats, dogs and monkeys. Dosages injected were 10(-4) M, 10(-3) M and 10(-2) M in 10 rats; 10(-4) and 10(-3) M in five dogs and five monkeys. The volume of drug injected was 0.05 ml for the rats and 0.5 ml for dogs and monkeys. The results show a dose-dependent erectile response to sodium nitroprusside injection (mean intracavernous pressure increase of 102.4 cm H2O in dogs, and 98.4 cm H2O in monkeys after injection of 10(-3) M nitroprusside). However, only a slight increase in intracavernous pressure (mean increase 28.4 cm H2O after injection of 10(-2) M of sodium nitroprusside) was noted in rats. The drop in blood pressure was > 15 mmHg in dogs and monkeys, while in rats it varied according to the dose studied. Sodium nitroprusside induced excellent erections in dogs and monkeys with minimal alteration in blood pressure. However, administration in rats resulted in hypotension. Nitroprusside may not be an acceptable nitric oxide donor for the treatment of male erectile dysfunction.

The distribution of elastic fibrous elements within the human penis.

OBJECTIVE: To determine the distribution of elastic fibres in the tunica albuginea and the erectile tissue of the penis. MATERIALS AND METHODS: Samples of tunica albuginea or penile erectile tissue were taken from seven cadavers and five patients undergoing surgery. Light and electron microscopy were performed. RESULTS: There were two anatomical regions in which elastic fibres were seen rarely: the proximal crus and the distal tunica. In the rest of the corpora cavernosa where the tunica was more compliant, the elastic fibres were in relative abundance. In the corpus spongiosum, abundant irregularly oriented elastic fibres were present; the densest elastic network was found in the glans penis and was composed of coarse elastic fibres. A perisinusoidal fibroelastic shell was seen in the glans, which was probably an extension of Buck's fascia. The elastic components within the sinusoids (cavernosal, spongiosal, and glanular) were similar but finer than the elastic lamellae in the penile arterial wall. CONCLUSION: The elastic fibres were unevenly distributed, often forming an irregular network on which the collagen component rested. Elastic fibres were more abundant in the corpus spongiosum, around the blood vessels and surrounding the sinusoid of the corpus cavernosum.

Anatomy and strength of the tunica albuginea: its relevance to penile prosthesis extrusion.

In 7 male cadavers the anatomical structure, thickness and tensile strength of the tunica albuginea of the penis, measured at specific locations, were determined. The tunica is composed of inner circular and outer longitudinal layers made up of collagen bundles. The outer layer appears to determine, to a large extent, the variation in thickness and strength of the tunica. The ventral groove (found between the 5 and 7 o'clock positions), which houses the corpus spongiosum, lacks outer bundles and appears vulnerable to perforation. The thickness of the tunica measured at the 7, 9 and 11 o'clock positions was 0.8 +/- 0.1 mm, 1.2 +/- 0.2 mm and 2.2 +/- 0.4 mm, respectively. Differences in the thickness of the tunica at specific locations were statistically significant (all p < or = 0.018). Symmetrical measurements were nearly identical in a mirror image arrangement (3, 5 and 1 at the 9, 7 and 11 o'clock positions, respectively). The stress on the tunica at penetration (breaking point pressure) measured at the 7, 9 and 11 o'clock positions was 1.6 +/- 0.2 x 10(7) N/m.2, 3.0 +/- 0.3 x 10(7) N/m2 and 4.5 +/- 0.5 x 10(7) N/m.2, respectively. The strength and thickness of the tunica correlated in a statistically significant manner with location (r = 0.911 and p = 0.0001). The most vulnerable area is on the ventral aspect (which lacks the longitudinally directed outer layer bundles), where most prostheses tend to extrude. This finding supports our belief that prosthesis extrusion often has an anatomical basis and is not merely a phenomenon caused by infection or compression.

Rat model for the study of penile erection: pharmacologic and electrical-stimulation parameters.

We report the use of a modified rat model for the study of the mechanisms of penile erection. In 92 Sprague-Dawley rats, the cavernous nerve was stimulated with different pulse intensities and frequencies, and the intracavernous pressure, time to maximal pressure and total duration of tumescence were measured. A maximal response was elicited at 20 pulses per second (pps) and 1.5 mA. Using this as 100%, we determined the relative pressure responses obtained with other frequencies: 5 pps, 57.3% (p = 0.007), 10 pps, 84.9% (p = 0.043); 30 pps, 99.5% (p = 0.832); 40 pps, 97.8% (p = 0.168); 50 pps, 90.9% (p = 0.021); 100 pps, 76.1% (p < 0.001). The time to maximal pressure varied with different frequencies, but was in all cases significantly different from the 20-pps response. Erection time during continuous cavernous nerve stimulation was significantly longer with frequencies below 20 pps (10 and 5 pps). In 30 rats, the physiologic response to intracavernous injection (0.03 ml) of acetylcholine, atropine, guanethidine, norepinephrine, phenylephrine, papaverine, terbutaline (intravenous also) and phentolamine was measured. Papaverine caused a dose-dependent rise in pressure; acetylcholine, atropine (a parasympathetic blocking agent) and guanethidine all had minimal effects. Phentolamine and norepinephrine increased systemic blood pressure, whereas phenylephrine decreased the intracavernous pressure in response to electrostimulation significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular mechanism of penile erection in monkeys.

To elucidate the sequence of events between the release of neurotransmitters and cavernous smooth muscle relaxation in erection, we studied the role of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems. In a well-established simian model, the effects of specific agonists and antagonists of the intracellular sequence for smooth muscle relaxation and potassium channel openers on the intracavernous pressure were examined. Sodium nitroprusside (10(-3) M), a nitric oxide releaser and thus a stimulant of the cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm H2O for 7 to 19 min and penile diameter from 24.8 +/- 2.28 to 43 +/- 4.87 mm. When nitroprusside was injected after methylene blue (10(-3) M), a specific antagonist of the enzyme guanylate cyclase, intracavernous pressure rise decreased significantly, but cromakalin, a potassium channel opener, provoked excellent increases after the block. A smaller dose of sodium nitroprusside (10(-4) M) caused an increase in intracavernous pressure from 35 to 85 cm H2O for 7 to 11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase inhibitor, the increase in pressure ranged from 80 to 116 cm H2O for 15 to 30 min. Prostaglandin E1, an activator of the cAMP system, caused an increase in the intracavernous pressure of 20-80 cm H2O for 5 to 10 min, and an increase in penile diameter from 25 +/- 2.22 to 35 +/- 3.48 mm. The erectile response to PGE1, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate cyclase blocker. The response to nitroprusside was significantly greater (P < 0.05) than to PGE1. Both systems, cAMP and cGMP, may be involved in cavernous smooth muscle relaxation, and cGMP is probably the predominant intracellular second messenger in penile erection in monkeys. Stimulants of the cGMP system, such as nitric oxide releasers, could represent a more physiological and effective approach in the treatment of erectile dysfunction.

Can a venous patch graft be a substitute for the tunica albuginea of the penis?

We describe our experience with plaque excision and placement of a venous patch graft. Sprague Dawley rats (n = 20) underwent excision of a wedge of tunica albuginea with the defect covered by a segment of detubularized femoral vein, endothelial side towards the cavernous tissue. Erectile function, as determined by the rise in intracavernous pressure with cavernous nerve stimulation (mean 54.0 +/- 4.2 cm. H2O), was equal to that in a group of 10 intact age-matched controls (mean 46.9 +/- 3.37 cm. H2O). Penile cross-sections stained with Hart's elastic fiber stain or Trichrome stain revealed only minimal fibrosis in the region of the patch. In 3 dogs, a wedge of tunica was removed, and the defect was covered with a segment of detubularized deep dorsal vein. When sacrificed at 3 months, all animals had retained their erectile function with histologic evidence of minimal fibrosis. On the basis of histologic and functional data, the venous patch appears to be a reasonable alternative substance to those in common use.

Combined cavernous compression device and arteriovenous-cavernous fistula: a chronic canine model.

In 5 dogs studied over a 3-month period, we evaluated the chronic effects of the combination of deep dorsal vein arterialization with implantation of an inflatable venous compression device. The device was placed around the proximal corpora cavernosa, sparing the left dorsal artery. A left-to-right, end-to-side dorsal artery-dorsal vein fistula was fashioned, and the right dorsal vein was anastomosed to the corpus cavernosum as an end-to-side venocorporeal window. From postoperative day 15, the device was activated twice a day for 3 months. Intracavernous pressure (bilateral) and left dorsal artery blood flow were monitored, and the patency of the anastomoses was evaluated by vascular clamping, arteriography, cavernosography and microscopic dissection. The device was well-tolerated, requiring no anesthesia during activation. (A sixth dog developed glanular hyperemia and priapism and was excluded from evaluation). With cuff inflation, the intracavernous pressure was significantly higher on the experimental side (range, 20 to 106 cm. H2O higher; p = 0.028), and arteriography demonstrated contrast flowing in the fistula and window in 3 of 4 dogs in which it was done. Both clamping and microscopic dissection of the specimen showed patency of the anastomoses in all 5 dogs. Histologic examination revealed maintenance of normal cavernous tissue histology.

The role of cyclic adenosine monophosphate, cyclic guanosine monophosphate, endothelium and nonadrenergic, noncholinergic neurotransmission in canine penile erection.

To elucidate the neuropharmacology of erection, we undertook an in vivo canine study to examine the role of cholinergic and nonadrenergic, noncholinergic (NANC) neuroeffectors and the sinusoidal endothelium in erection induced by electrostimulation. We also examined the effect of adenylate cyclase and guanylate cyclase blockers by intravenous injection of N-ethylmaleimide and methylene blue, respectively. In addition, the effects of intracavernous injection of the nitric oxide-releasing substance, nitroprusside, and bromocyclic adenosine monophosphate (AMP) and bromocyclic guanosine monophosphate (GMP) were also studied. In contrast to in vitro results, atropine reduced the increase of intracavernous pressure after neurostimulation (p = 0.029). Intracavernous injection of CHAPS to destroy the sinusoidal endothelium abolished the response to acetylcholine (p = 0.001), but only partially inhibited the response to electrostimulation (mean = 75% pressure increase, p = 0.022), indicating that neuronal nitric oxide plays a major role in penile erection. Methylene blue, a guanylate cyclase inhibitor, significantly inhibited the erectile response to both neurostimulation and sodium nitroprusside (p = 0.000 and 0.017, respectively). However, N-ethylmaleimide, an adenylate cyclase inhibitor, could not reduce the response to neurostimulation (p = 0.078). The erectile response to intracavernous injection of cGMP was significantly better than that induced by cAMP (p = 0.025). Our results suggest that both the cholinergic and NANC neuroeffectors and the sinusoidal endothelium are involved in erection. In addition, our data imply that the neuronal nitric oxide/cyclic GMP system is the most likely pathway for penile smooth muscle relaxation and erection.

Cyclic guanosine monophosphate mediates penile erection in the rat.

Recent in vivo and in vitro studies suggest that nitric oxide or a nitric-oxide-like substance mediates nonadrenergic, noncholinergic relaxation of trabecular smooth muscle through activation of the cyclic guanosine monophosphate (cGMP) pathway. In 60 Sprague-Dawley rats, we investigated the effect of intracavernous administration of different drugs known to act at different levels of the cyclic adenosine monophosphate (cAMP) and cGMP pathways. Neither cAMP nor drugs that stimulate adenylate cyclase activity (vasoactive intestinal peptide, prostaglandin E1, calcitonin gene-related peptide) provoked any change in the basal intracavernous pressure. N-ethylmaleimide, an inhibitor of the enzyme adenylate cyclase, did not modify the response to electrostimulation of the cavernous nerve, indicating that the cAMP pathway does not play a significant role in penile erection in rats. However, intracavernous administration of methylene blue, a guanylate cyclase inhibitor, significantly reduced the response to electrostimulation (p = 0.001). Direct intracavernous injection of cGMP caused a statistically significant, dose-dependent increase in intravenous pressure that was not significantly inhibited by methylene blue. Sodium nitroprusside, a nitric oxide releaser and therefore a guanylate cyclase activator, caused a dose-dependent increase in intracavernous pressure (p < 0.05) that was inhibited almost completely by methylene blue (p = 0.002), supporting the theory that nitric oxide activates the synthesis of cGMP and that cGMP causes cavernous smooth muscle relaxation. Papaverine elicited an intracavernous pressure increase that was not affected by methylene blue or N-ethylmaleimide, indicating that papaverine acts through an independent pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of bladder, urethral and intracavernous pressure to ventral lumbosacral root stimulation in Sprague-Dawley and Wistar rats.

Six Sprague-Dawley and six Wistar rats were used for electrostimulation of the L5 to S2 ventral roots. Landmarks for identification of the roots were developed; bladder, urethral and intracavernous pressures were recorded; and tail and leg movements were checked. Urethral sphincter contraction was elicited by stimulation of the L5-L6 ventral roots, while bladder contraction and penile erection were mediated by the L6-S1 ventral roots. The best sphincteric response and intracavernous pressure rise were obtained by stimulation of the L6 ventral root, and the highest bladder pressures by stimulation of the S1 ventral root. Stimulation of the S1-S2 ventral roots provoked ipsilateral tail movement; of L6, tail movement, hindleg muscle twitch, and slight toe spread; and of L5, hindleg stretch and plantar flexion. No significant differences were found between the two strains of rats, although a higher bladder pressure was recorded during stimulation of the L6 ventral root in Sprague-Dawley rats, which might be explained by a small caudal shift of the sacral parasympathetic nucleus in the Wistar strain.