Wolfgang Diederichs

ULTRASTRUCTURAL CHANGES IN IMPOTENT PENILE TISSUE : A COMPARISON OF 65 PATIENTS

To determine whether impotence is caused by specific and consistent changes in erectile tissue, we compared the ultrastructure of the corpora cavernosa in 6 controls with that in 59 patients undergoing implantation of a penile prosthesis. The impotent patients were divided into groups based on a medical history of hypertension (10), pelvic surgery (9), alcoholic smokers (8), hypertensive alcoholics (3), hypertensive alcoholic smokers (3), smokers (3), diabetics (8), diabetic smokers (3), Peyronies disease (3), spinal cord injury (3) and isolated causes (6). Our data demonstrate that different behavioral and/or medical conditions produce similar degenerative tissue responses. There is no single or specific cause of impotence that is manifest by consistent changes in erectile tissue.

Correlation of altered penile ultrastructure with clinical arterial evaluation.

We investigated the ultrastructural changes in the penile erectile tissue from 32 consecutive patients who underwent penile prosthesis implantation. Because most of the patients had undergone papaverine injection with or without duplex ultrasonography, we compared these results with the electron microscopic findings. In patients with a good arterial response and full erection after papaverine injection the ultrastructural findings were similar to those reported in normal men. In patients with moderate arterial disease a distinct increase in mitochondria with aggregation and cytoplasmic vacuolization in smooth muscle cells was noted. These findings could be interpreted as an active cellular attempt to respond to the altered environmental and nutritive situation. In patients with severe arterial insufficiency the cellular structure was markedly altered, the number of intracavernous smooth muscle cells was reduced and the density of the connective tissue separating individual cells was increased. These changes in the smooth muscle cells consisted of contour irregularity with fragmentation and loss of the basal lamina. The cytoplasm was largely devoid of contractile elements. The nuclei tended to be pleomorphic with unevenly distributed chromatin. The endothelium was also altered significantly in this group. A careful clinical evaluation of penile arterial function should be performed in all patients undergoing penile arterial or venous corrective surgery. If doubt remains, a penile biopsy may be indicated.

Norepinephrine involvement in penile detumescence.

Adrenergic neurotransmission was studied in dogs. Blood samples for catecholamine assay were collected from the flaccid penis, the erect penis after cavernous nerve stimulation and during detumescence induced by sympathetic trunk stimulation. Epinephrine concentration was not significantly different in these three stages. However, norepinephrine concentration increased significantly (p less than 0.005) during induced detumescence from 505 +/- 311 [pg./ml.] to 747 +/- 489 [pg./ml.]. Intracavernous application of norepinephrine abolished cavernous nerve induced erection in a dose dependent manner. Sympathetic trunk stimulation reduced or abolished erection induced by acetylcholine or by vasoactive intestinal polypeptide. We conclude that norepinephrine is an important neurotransmitter in the control of penile detumescence.

Sympathetic Inhibition of Papaverine Induced Erection

We studied the effect of neurostimulation of the lumbar sympathetic trunks on papaverine-induced penile erection in dogs and monkeys. The mean of 124 cm. H2O intracavernous pressure after papaverine injection was reduced under sympathetic trunk stimulation to 40.6 cm. H2O within a mean of 39 sec. In addition the flow of the internal pudendal artery was reduced indicating a decrease of the inflow to the penis. After the sympathetic stimulation was terminated, the intracavernous pressure increased again to the same level as before. This pressure recovery time was delayed after several sympathetic stimulations from 134 sec. (5 min. after papaverine injection) to at least 362 sec. (45 minutes after papaverine injection). Stimulation of the inferior hypogastric plexus had no effect on the intracavernous pressure. The neurostimulation range (3-4V; 20 Hz) was most effective in reducing the papaverine action on penile smooth muscles. The effect of sympathetic trunk stimulation seems to antagonize the relaxing action of papaverine on the cavernous smooth muscles and the cavernous arterioles. Our results imply that high sympathetic tone in some patients with psychogenic impotence may explain their poor response to intracavernous injection of papaverine.

The Effect of Subatmospheric Pressure on the Simian Penis

The effects of subatmospheric pressure on the simian penis were studied in nine monkeys under anesthesia. A plastic cylinder was placed over the penis and suction applied until the gauge pressure was -100 to -200 cm. H2O. The intracavernous pressure decreased within one to three seconds to between -60 and -120 cm. H2O followed by a gradual increase as a result of blood flow into the corpora cavernosa. The intracavernous pressure recovery was 50% after 17 seconds and 100% by 30 to 60 seconds. These effects could also be observed when the penile base was partially constricted with a rubber band before applying the partial vacuum. Tumescence resulting from suction disappeared immediately when suction was terminated unless the base of the penis was constricted before and after the application of vacuum. In the latter case tumescence was prolonged (cavernous pressure between 60 and 120 cm. H2O) after suction. The cross-sectional area of the penis expanded to more than 150% of the flaccid state. The increase of intracavernous pressure from intracavernous papaverine injection was similar to that after suction with a constricting rubber band in place at the base of the penis. Subatmospheric pressure induces an expansion of the penis followed by increased blood inflow. The additional volume can be kept in the penis only if a constriction device is placed at the base of the penis. The tumescence induced by suction is passive, occurring without evidence of smooth muscle relaxation or release of neurotransmitters.

The sympathetic role as an antagonist of erection

SummaryThe effects of the lumbar and pelvic sympathetic system on penile erection were studied in a canine model. Erection was induced by cavernous nerve stimulation and detumescence by sympathetic trunk stimulation. Erection induced by cavernous nerve stimulation normally subsides slowly. After discontinuation of electrical stimulation the intracavernous pressure drops within a mean of 291 s to 50% and after a mean of 372 s to 10% of the highest level. However, stimulation of the sympathetic trunk at the level of L4-S1 applied directly after discontinuation of cavernous nerve stimulation accelerated this drop of intracavernous pressure significantly: to 50% after a mean of 19 s and to 10% after a mean of 36 s. If stimulation of the sympathetic trunk was initiated 20 s before cavernous nerve stimulation, the pressure rise was aborted completely. Neurostimulation of the hypogastric nerves alone or in combination with cavernous nerve stimulation did not change the intracavernous pressure. These results were not altered after neurotomy of the pudendal or hypogastric nerves. The main pathway of the fibers from the sympathetic trunk to the penis seems to run via the pelvic plexus. The stimulation voltage and frequency to induce erection or detumescence were equivalent. Our results suggest that an elevated central sympathetic tone may be one of the causes of psychogenic impotence.

The diagnosis of venogenic impotence: dynamic or pharmacologic cavernosometry?

In an attempt to refine the diagnosis of venogenic impotence, we evaluated different techniques of cavernosometry in 10 dogs. Saline was perfused intracavernously in five dogs to induce erection. Regardless of the amount required for induction, a mean flow rate of 23.4 ml./min. was necessary to maintain an intracavernous pressure level of 110 cm. H2O. In seven dogs, a leak was created by intracavernous insertion of a 19-gauge needle. When erection was induced by either cavernous nerve stimulation or a combination of papaverine injection and saline perfusion, the mean flow through the needle was significantly less than when erection was induced by saline perfusion alone (1.73, 1.78, and 8.77 ml./min., respectively). Sympathetic trunk stimulation at the level of L5 could reduce the intracavernous pressure by 90% in erections induced by neural stimulation or papaverine plus perfusion but had no effect on erection induced by saline perfusion alone. Our findings show that cavernosometry after intracavernous injection of papaverine will provide more valuable information in patients in whom venogenic impotence is suspected.

The Rationale for Pharmacologic Cavernosography

To refine the diagnostic method for opacification of aberrant venous drainage in venogenic impotence, an experimental study was done in eight monkeys. In all monkeys, cavernosography after induction of erection by saline perfusion showed significant drainage via the cavernous veins. However, when cavernosography was performed after neurostimulation or papaverine injection, no cavernous drainage was visualized, even when the intracavernous pressure had been significantly lowered by creation of an artificial cavernous leak. Because erection can result from saline perfusion only when the volume perfused exceeds the venous outflow capability, cavernosography during saline-induced erection will always demonstrate the entire venous system and, thus, is of no diagnostic value. Pharmacocavernosography imitates the physiologic venous occlusive mechanism and should therefore be used to identify the abnormally draining veins in venogenic erectile dysfunction.

Possible Role for Acetylcholine as a Neurotransmitter in Canine Penile Erection

In 15 adult dogs, the possible role of acetylcholine as a parasympathetic neurotransmitter in canine penile erection was investigated. Intracavernous injection of increasing dosages of acetylcholine (0.1-100 micrograms) induced a dose-dependent erectile response with increased arterial flow, cavernous smooth muscle relaxation, and venous occlusion. This erectile response was completely abolished after muscarinic blockade by intracavernous injection of 0.1 mg atropine. After cavernous nerve stimulation, atropine injection significantly reduced the pudendal arterial flow (by 25%) and likewise caused a significant reduction in cavernous outflow restriction. Histologic staining showed acetylcholinesterase-positive fibers around the cavernous arteries and within the cavernous erectile tissue.

Reduction of sympathetic influences on penile erection by phentolamine.

The lumbosacral sympathetic trunks seem to play a major role in penile detumescence. In animal experiments an erection induced by cavernous nerve stimulation can be abolished by neurostimulation of the canine sympathetic trunks. This canine experiment was designed to study the possible reduction of the sympathetic effect by intravenous injection of phentolamine. The aborted erection by sympathetic trunks stimulation was partially antagonized by phentolamine. The arterial flow to the penis as well as the intracavernous pressure were elevated by this drug. As an expected side effect the systemic arterial blood pressure decreased by 4-14 cm H2O after phentolamine injection.