Do penile haemodynamics change in the presence of hydrogen sulphide (H2S) donor in metabolic syndrome‐induced erectile dysfunction?

Erectile dysfunction (ED) is defined in relation to the metabolic syndrome (metS). Hydrogen sulphide (H₂S), a gasotransmitter, has been revealed to get involved in hypertension, insulin secretion and regulation of vascular tone especially in erectile physiology. This study aimed to investigate the effect of H₂S on metS‐induced ED. Animals were divided into two groups as control and metS, which were fed with standard diet or 60% high‐fructose diet for 10 weeks respectively. The metS model was evaluated with biochemical analyses, waist circumference/tibia length ratio and HOMA index. Penile hemodynamic parameters were evaluated by the measurement of intracavernous pressure/mean arterial pressure ratio during cavernous nerve stimulation in the presence and absence of intracavernous injection of NaHS (100 μg/50 μl) and its control 0.9%NaCl (50 μl) in both groups. H₂S levels were measured in penile tissues by methylene blue assay. H₂S levels were significantly decreased in the penile tissues of the metS group. Decreased intracavernous pressure/mean arterial pressure ratio improved after intracavernous administration of NaHS in the metS group. These results suggest the significant role of H₂S in the metS‐induced erectile dysfunction that could be a new therapeutic target.     

Three‐dimensional CT cavernosography: reconsidering venous ligation surgery on the basis of the modern technology

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Venous ligation surgery has been conducted as a symptomatic treatment, but the effective rate of this surgery was insufficient. We thought that one of the reasons for the low effective rate of this surgery was insufficient for the diagnostic modality. We confirmed that 3D cavernosography was, in comparison with conventional cavernosography, higher in diagnosis precision.

OBJECTIVE

• ? To examine the feasibility of three‐dimensional (3D) CT cavernosography in the diagnosis of corporal veno‐occlusive dysfunction.

PATIENTS AND METHODS

• ? The subjects were 55 patients who had failed to respond to phosphodiesterase type 5 inhibitors. We performed pharmacodynamic infusion cavernosometry and cavernosography, using 60 mg papaverine hydrochloride.
• ? Cavernosography was performed at 90 mmHg intracavernous pressure, using a multi‐slice CT scan system. The 3D images were reconstructed using aquarius net station , ver.2 computer software.
• ? For comparison with conventional cavernosography, maximum intensity projection (MIP) images were used. A flow of 20 mL/min or being more capable of maintaining 90 mmHg of intracavernous pressure indicated veno‐occlusive dysfunction.

RESULTS

• ? Forty‐five of the 55 patients were diagnosed with corporal veno‐occlusive dysfunction. 3D‐CT cavernosography revealed drainage veins in all 45 cases, including cavernous veins, dorsal veins, crural veins and other emissary veins.
• ? Compared with 3D‐CT cavernosography, observing cavernous veins and the proximal part of the deep dorsal veins using MIP imaging was especially difficult because the origins of the penile veins are often behind the pelvic bone or cavernous body.
• ? Of the patients who seemingly had leakage via the deep dorsal vein, 80.6% did not in fact have leakage via this vein, but had other leakages. The image resolution of 3D‐CT cavernosography was significantly higher than that of MIP.

CONCLUSION

• ? 3D‐CT cavernosography can provide high‐resolution images of venous drainage from any angle. We conclude that the images obtained by 3D‐CT cavernosography are very helpful for both the diagnosis of corporal veno‐occlusive dysfunction and the anatomical study of the human penile venous system.

     

The Presence of Arterial Anatomical Variations Can Affect the Results of Duplex Sonographic Evaluation of Penile Vessels in Impotent Patients

Purpose

Since penile arterial communications are present in a significant percentage of impotent patients, we evaluated whether peak systolic cavernous blood velocity after intracavernous prostaglandin E1 injection might be different in patients with and without arterial variants.

Materials and Methods

Cavernous blood flow was assessed with echo color Doppler ultrasound before and after intracavernous injection of prostaglandin E1 in 63 impotent patients. The penile shaft was accurately evaluated to detect arterial anatomical variants. Clinical erectile response was assessed by visual inspection and palpation.

Results

Of 23 patients who obtained a full erection with full rigidity after prostaglandin E1 injection the cavernous peak blood velocities in 11 with penile arterial communications were significantly less than those in 12 without arterial communications.

Conclusions

The generally accepted limit of normal for cavernous peak blood flow obtained after prostaglandin E1 injection (greater than 25 to 30 cm. per second) must be interpreted carefully because lower peak blood velocities may be found in subjects with a full erectile response if arterial communications are present.     

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.     

Evaluation of a no-needle penile injector: a preliminary study evaluating tissue penetration and its hemodynamic consequences in the rat

Objectives

Intracavernous needle injection is an effective delivery method for pharmacotherapy of erectile dysfunction. Needle phobia, pain, and concern about local tissue injury have stimulated the search for new, less invasive means of inducing penile erection. In this preliminary communication, we evaluate a jet injector as an alternative to needle injection for intracavernous delivery of vasoactive drugs.

Methods

Jet injection was evaluated in three groups of rats receiving either India ink, saline, or papaverine into the penis. The ability of the jet injection to penetrate through the tunica albuginea and deliver liquid to the corpora cavernosa smooth muscle was assessed by the degree of staining within the corpus cavernosum (ink group), histologic change (saline group), and rise in intracavernous pressure (papaverine group). Erectile capacity following cavernous nerve electric stimulation was compared before and 1 hour after injection of saline or papaverine.

Results

Ink traversed the skin and tunica albuginea with extensive deposition noted within the cavernous spaces. Varying degrees of subcutaneous hemorrhage were seen with saline jet injection; however, the corpus cavernous smooth muscles showed no evidence of injury. Jet injection of papaverine 3250 gmg significantly increased cavernous pressure (39.4 ± 4.6 cm H₂O) compared with saline injection (2.8 ± 1.3 cm H₂O).

Conclusions

We conclude that acute jet injection is an effective method for intracavernous delivery of drugs. Long-term effects should be evaluated prior to clinical use.     

The rabbit as an intracavernous injection study model

We investigated the feasibility of using the rabbit as an animal model for intracavernous injection studies. The rabbit, having a penile structure rather similar to that of humans, offers the advantage of being a strain-specific, adequately sized, and easily controlled experimental animal. Using intracavernous injections of the two vasoactive drugs prostaglandin E₁ (PGE₁, 0.2–1.6 g/kg) and papaverine (PAP, 0.25–1 mg/kg), which have been commonly used in the management of erectile dysfunction in man, increases intracavernous injection of PGE₁m the maximal ICP ranged from 18 to 44 mmHg (mean 29.25±7.85 mmHg) with a duration of tumescence from 3.1 to 13.3 min (mean 8.61±3.71 min). Intracavernous injection of PAP also induced increases in ICP, with a maximal ICP ranging from 24 to 56 mmHg (mean 43.5±11.35 mmHg) and a duration of tumescence from 5.3 to 15 min (mean 10.25±3.39 min). The systemic blood pressures were unchanged after all intracavernous injections. In addition, administration of cAMP antagonist in combination with PGE₁ inhibited the relaxing effects of PGE₁ in a dose-dependent manner. Our results suggest that the effects of vasoactive drugs on the rabbit's corpus cavernosum are similar to those in humans; thus the rabbit model is a suitable alternative for further physiological and pharmacological studies of penile erection.     

Experience with penile circular fasciocutaneous flap in the treatment of long anterior urethral strictures

Objective  

To evaluate our experience with penile circular fasciocutaneous flap urethroplasty for the repair of long penile and bulbar strictures.     

Tunica‐sparing ossified Peyronie’s plaque excision

Study Type – Diagnostic (non‐consecutive series) Level of Evidence 3b What’s known on the subject? and What does the study add? Peyronie’s disease with heterotopic, ossified plaques require surgical removal. While conventional tunical excision techniques risk erectile and sensory compromise, we describe a tunical‐sparing technique which maintains potency with durable results.

OBJECTIVE

Ossified Peyronie’s plaques may require surgical excision because of the palpable problems and penile curvature that result. As tunical excision can result in impotence and decrease penile sensation, we describe a novel method of tunical preserving excision of such lesions.

PATIENTS AND METHODS

We evaluated 12 men with dorsal penile curvature between 10° and 90°. Penile plaque size ranged from 1 to 5 cm. 80% had painful erections. An artificial erection was induced with intracavernous injection of papaverine to assess penile deformity. Via a circumcising or ventral incision, plication sutures were placed to correct penile curvature. A lateral longitudinal corporotomy was made and the calcified/ossified portion was dissected free from the tunica albuginea/plaque of the corpora cavernosa. Watertight tunical closure was then performed.

RESULTS

Postoperatively, 80% of men reported erections always adequate for intercourse and normal sensation with a mean follow‐up of 7 months (range 2.1–14.5 months). All patients required simultaneous penile plication to ensure a straight phallus. Pathologic evaluation of plaque specimens all showed bone fragments.

CONCLUSION

Tunica‐sparing excision of the ossified/calcified portion of Peyronie’s plaques shows a durable benefit for large, ossified lesions and maintains potency and penile sensation.     

FUNCTIONAL ANATOMY OF CAVERNOUS HELICINE ARTERIOLES IN POTENT SUBJECTS

Purpose

We investigated the morphological and functional features of cavernous helicine arterioles in male potent subjects.

Materials and Methods

Ten young men reporting normal rigid erections which were confirmed by polysomnographic recording underwent power Doppler sonography of the cavernous helicine arterioles during flaccidity, after intracavernous injection of alprostadil, and after subsequent genital and audiovisual sexual stimulation.

Results

During flaccidity the helicine arterioles were never detected by power Doppler imaging while they became evident in all cases after alprostadil injection. They usually originated from the cavernous artery forming an acute angle and showed 3 orders of ramifications. Systolic and diastolic flow was present. After genital and audiovisual sexual stimulation, and achievement of maximum rigidity, the helicine arterioles were still evident but with only 1 or 2 orders of distal ramifications. Only systolic flow was present. During penile tumescence the helicine arterioles disappeared in all cases.

Conclusions

Using power Doppler sonography it is possible to investigate the functional anatomy of the cavernous helicine arterioles during the various phases of the erectile cycle. Our preliminary study suggests that the helicine arterioles are functionally inactive during penile flaccidity while they are activated during penile tumescence and continue to supply blood to the corpora also during maximum penile rigidity.     

The Evaluation of Arterial Inflow by Gravity Cavernosometry

Purpose

We determined whether the comparison between equilibrium pressure after intracavernous injection of vasodilators and maximal corporeal pressure at gravity cavernosometry could provide information about the relative contribution of arterial inflow and cavernous wall resistance to the erection process.

Materials and Methods

The results of gravity cavernosometry performed in 68 impotent patients were compared to those of duplex scanning in 53 and penile angiography in 10.

Results

A highly statistically significant (p <0.01) but nonlinear correlation was observed between the equilibrium pressure after injection and maximal corporeal pressure, which indicates a paramount role of the corporeal veno-occlusive mechanism in the development of penile rigidity. However, in most patients with a pressure increase of more than 30 mm. Hg from the equilibrium pressure after injection to the maximal corporeal pressure, arterial insufficiency was diagnosed by duplex scanning and/or arteriography, and seemed to be the main limiting factor in the development of penile rigidity.

Conclusions

Gravity cavernosometry provides functional information about the corporeal veno-occlusive mechanism and arterial inflow and, therefore, about the relative roles of these mechanisms in the development of penile rigidity.     

The role of vacuum pump therapy to mechanically straighten the penis in Peyronie’s disease

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To assess the efficacy of vacuum therapy in mechanically straightening the penile curvature of Peyronie’s disease (PD).

PATIENTS AND METHODS

Modelling of the tunica albuginea has been shown to be possible during penile implant surgery and this principle has been applied as an alternative conservative therapy. In all, 31 patients with PD (mean duration 9.9 months; mean age 51 years, range 24–71) completed the study. Over a 12‐week period, the patients used a vacuum device (Osbon ErecAid®, MediPlus, High Wycombe, UK) for 10 min twice daily. The assessment at study entry and at completion after 12 weeks included the International Index of Erectile Function questionnaire, a perceived pain intensity score, stretched penile length measurement and the angle of penile deformity after an intracavernous injection with prostaglandin E1.

RESULTS

There was a clinically and statistically significant improvement in penile length, angle of curvature and pain after 12 weeks of using the vacuum pump. Of the 31 patients, 21 had a reduction in the angle of curvature by 5–25°, three had worsening of the curvature and there was no change in the remaining seven. The curvature was corrected surgically in 15 patients while the remaining 16 (51%) were satisfied with the outcome.

CONCLUSION

Vacuum therapy can improve or stabilize the curvature of PD, is safe to use in all stages of the disease, and might reduce the number of patients going on to surgery.     

Surgical Treatment of Peyronie's Disease by Plaque Incision and Grafting with Buccal Mucosa

Background

Plaque incision and tunical grafting is widely used to correct penile curvatures secondary to Peyronie's disease (PD), but there is no consensus on the ideal graft to be used.

Objective

To evaluate the efficacy, safety, and reproducibility of plaque incision and buccal mucosa grafting (BMG) in the correction of severe penile curvatures secondary to PD.

Design, setting, and participants

Fifteen patients reporting normal erections and stable curvature (>12-mo duration) entered this prospective study carried out at two university hospitals.

Intervention

All patients underwent plaque incision and BMG.

Measurements

Preoperative evaluation included the International Index of Erectile Function (IIEF-5) and penile duplex ultrasounds with measurement of curvature and length of affected side. Follow-up visits were scheduled at 1, 3, 6, and 12 mo postoperatively, then yearly. Three-mo postoperative evaluation included IIEF-5, patient and partner satisfaction, and intracavernous injection test with evaluation of penile rigidity, straightness, and length; patient and partner satisfaction was recorded at all subsequent visits.

Results and limitations

Mean patient age was 56.3 yr and mean penile curvature 72°; five patients had a two-sided curvature with mean second curvature of 37°. There were no complications. All patients resumed unassisted intercourse 1 mo after surgery. Three-mo postoperative evaluation showed 100% penile straightening, 1.8-cm mean increase in length of affected side, no curvature recurrence or de novo erectile dysfunction, 1.6 mean increase in IIEF-5 score, and patient and partner satisfaction of 93.3% and 100%, respectively. Although results remained stable at subsequent follow-up (mean 13.1 mo), a greater number of patients and longer follow-up are needed before drawing any definite conclusions.

Conclusions

BMG provided excellent short-term results, probably because its prompt revascularisation, suggested by the fast return of spontaneous erections, prevented shrinkage, which is the main cause of graft failure. It also proved to be safe and reproducible, thus representing a valuable treatment option for PD.     

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. © 1994 Wiley-Liss, Inc.     

In vitro and in vivo studies on the importance of the soluble guanylyl cyclase α1 subunit in penile erection

Purpose  

Soluble guanylyl cyclase (sGC), which plays a pivotal role in penile erection, is a heterodimer build up by an α and a β subunit. For both subunits two isoforms have been characterized, but only the sGCα₁β₁ and sGCα₂β₁ isoforms seem to be functionally active. To elucidate the functional role of the sGCα₁β₁ heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGCα₁^−/− mice.     

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients

Background  

To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage).     

The timing of penile rehabilitation after bilateral nerve‐sparing radical prostatectomy affects the recovery of erectile function

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To define if erectile function (EF) outcomes were better in men with early institution of penile rehabilitation after radical prostatectomy (RP), as one of the mechanisms by which patients fail to recover EF after RP is collagenization of corporal smooth muscle with subsequent venous leak development, and rehabilitation is aimed at preventing these structural alterations.

PATIENTS AND METHODS

The study population comprised patients who: (i) had clinically organ‐confined prostate cancer; (ii) had fully functional erections, corroborated by the partner; (iii) had bilateral nerve‐sparing RP; and (iv) committed to pharmacological penile rehabilitation. Patients completed the International Index of Erectile Function (IIEF) serially after RP. Patients were instructed to obtain three erections/week using initially sildenafil, and if unsuccessful, then intracavernous injections. Patients were subdivided into those starting rehabilitation at <6 months after RP (early) and those starting at ≥6 months after RP (delayed).

RESULTS

There were 48 patients in the early group and 36 in the delayed group; patients in both groups were matched for age, comorbidity status and baseline EF. The mean duration after RP at the time of starting penile rehabilitation was 2 and 7 months in the early and delayed groups, respectively (P < 0.01). At 2 years after surgery there was a highly statistically significant difference in IIEF EF domain score between the early and delayed groups (22 vs 16, P < 0.001). There were also statistically significant differences between the groups in the percentage of men at 2 years after RP who had unassisted functional erections and sildenafil‐assisted functional erections (58% vs 30%, P < 0.01; 86% vs 45%, P < 0.01, respectively).

CONCLUSIONS

These data suggest that delaying the start of penile rehabilitation after RP is associated with poorer outcomes for EF.     

Penile Vascular Assessment Using Color Duplex Sonography in Men with Peyronie's Disease

Purpose

We assessed penile vasculature in men with Peyronie's disease using color duplex ultrasound.

Materials and Methods

A total of 99 consecutive men with Peyronie's disease underwent duplex ultrasound with 60 mg. intracavernous papaverine to gain an understanding of penile vasculature and its correlation to erectile rigidity. Patients were stratified into groups according to duplex ultrasound vascular parameters and the presence or absence of impotence (that is rigidity adequate for intromission).

Results

Of 97 men 31 (32 percent) complained of impotence, 8 of 99 (8 percent) had evidence of corporeal veno-occlusive dysfunction on duplex ultrasound (defined as end diastolic flow velocity greater than 4.5 cm. per second) and 43 percent had a history of vascular risk factors that may have contributed to erectile insufficiency. Impotent patients had decreased peak systolic flow velocity, increased end diastolic flow velocity and a higher percent of vascular risk factors (p = 0.0006, 0.027 and 0.0004, respectively) compared to potent patients.

Conclusions

Duplex ultrasound provides a dynamic noninvasive functional assessment of penile vasculature in Peyronie's disease. Although corporeal veno-occlusive dysfunction has been considered the primary vascular etiology of erectile dysfunction associated with Peyronie's disease, arterial insufficiency is a major contributor, which is best detected before definitive therapy.     

A novel modification of tunical plication by plaque thinning: long-term results in treating penile curvature of Peyronie’s disease

Objective  

To investigate the efficacy of a novel modified tunical plication procedure in correcting penile curvature of patients with Peyronie’s disease.     

Slow injection of prostaglandin E1 decreases associated penile pain

Objectives

A randomized, double-blind study to determine whether speed of intracavernous injection of prostaglandin E, (PGE,) is associated with pain.

Methods

On two separate occasions, using two different speeds of injection (5 versus 60 seconds), 11 subjects received the same dose of PGE, that they used at home. The presence, duration, and intensity of pain were recorded.

Results

We found that fast penile injection of PGE, was associated with a greater intensity of pain (P = 0.04).

Conclusions

Slow injection of PGE, is less often associated with penile pain, the most common adverse effect of this treatment.     

Modified annular penile skin flap for repair of pan-anterior urethral stricture

Objective  

To review our experience with a zigzag shape annular penile fasciocutaneous flap (modified McAninch flap) for reconstruction of pan-anterior urethral strictures.