Penile Pharmacocavernosography and Cavernosometry in the Evaluation of Impotence

0022-534 7/87 /1374-0772$02.00/0 Vol. 137, April

THE JOURNAL OF UROLOGY

Printed in U.S.A.

Copyright© 1987 by The Williams & Wilkins Co.

PENILE PHARMACOCAVERNOSOGRAPHY AND CAVERNOSOMETRY IN THE EVALUATION OF IMPOTENCE JOSEPH J. BOOKSTEIN,* KARIM VALJI, LOWELL PARSONS

AND

WARREN KESSLER

From the Departments of Radiology, University of California at San Diego and the Veterans Administration Hospital, San Diego and the Department of Urology, University of California at San Diego, San Diego, California

ABSTRACT

Within the past few years, veno-occlusion of the corpora cavernosa has become generally recognized as an essential prerequisite for adequate penile erection. Veno-occlusive incompetence is suspected to be a frequent cause of impotence. Our recent experience with cavernosography in two normal volunteers and 36 impotent patients indicates that angiography is reliable in evaluating the competence of the veno-occlusive mechanism only if both pharmacocavernosography (PCG) and pharmacocavernosometry (PCM) are applied. Twenty minutes after intracavernosal (IC) injection of a mixture of 60 mg. papaverine and one mg. phentolamine (regitine), 100 ml. of diluted radiographic contrast medium are infused at the rate of one or two ml./sec. while pressure is recorded, and radiographic films are exposed at the rate of one every eight to 15 seconds. PCM and PCG of the corpora cavernosa indicated the overall degree of competence of the cavernosal veno-occlusive mechanisms, and the sites of veno-occlusive incompetence; non-pharmacologic studies were unreliable in these regards. During non-pharmacologic infusion in normals, pressures rose to 40 to 45 mm. Hg, and free efflux could be visualized from multiple venous systems. After pharmacologic injection in normals, all venous channels closed, and pressures rapidly rose toward or above 200 mm. Hg, at which time the infusion was stopped. Veno-occlusive incompetence was defined angiographically when more than minimal efflux occurred during pharmacocavernosography from any venous system. The incompetence could involve the deep penile system, the deep dorsal system, or the spongiosal system, alone or in combination. Severe veno-occlusive incompetence was considered diagnostic of venogenic impotence, and was defined manometrically when IC pressures failed to exceed 100 mm. Hg during infusion of 100 ml. of fluid at 2 mm./second after IC papaverine and phentolamine injection. We believe these angiographic methods will improve the criteria against which other diagnostic and therapeutic methods can be assessed. A number of prior reports have described the usefulness of cavernosography and cavernometry in evaluating the status of the veno-occlusive mechanism. 1 • 2 Our non-pharmacologic studies of the corpora cavernosa however, gave variable and confusing results, and were not useful in differentiating patients vvit-h normal from those -v;lith abnormal veno-occlusive n1echanisms. It became apparent that evaluation of the veno-occlusive mechanism required both manometric and angiographic assessment during attempted activation. We have therefore developed such a method, based upon our laboratory experiences with a canine model,3 the infusion method of Puyau and Lewis,1 and clinical observations after IC administration of drugs. 4- 7 A similar technique has been published by Lue et al. 8 MATERIALS AND METHODS

Thirty-six patients with impotence of over three months duration underwent investigation with cavernosography and cavernosometry, with or without attempted pharmacologic activation of the veno-ocdusive mechanism. Most of these patients also had arteriography. At least one non-invasive parameter of organic impotence was usually present: decreased penilebrachial blood pressure index, or abnormal penile tumescence Accepted for publication October 15, 1986. *Requests for reprints: Dept. of Radiology, University of California, San Diego, Medical Center, 225 Dickinson St., San Diego, CA 92103. Supported by the Medical Research Service, Veterans Administration Hospital, San Diego, California, the Urological Research and Education Foundation and Meditec, Inc. 772

or rigidity test. Patient ages varied from 21 to 85, mean 54 ± 15 years. Trauma was the precipitating event in four patients. In addition, two sexually active and normal men (unsubstantiated self-claims), ages 57 and 61, with past ligation of the vas deferens, volunteered to undergo pharmacocavernosography (PCG) and phannacocavernosornetry (PCM). Arteriograms were not performed in these normals. Initial cavernosographic and manometric technique. The initial angiographic techniques are explained in the following paragraphs. Changes that evolved during the course of study, some of which have become standard, and important caveats, are indicated next. As experience, equipment and contrast agents change, further minor modifications will probably have been introduced by the time this manuscript comes to press. Procedures performed are indicated in table 1. Cavernosometry and cavernosography were generally preceded by arteriography. Following regional block of the base of the penis, using five ml. of 2% xylocaine deposited superficial to the tunica albuginea, 23 gauge needles were inserted obliquely into the dorso-lateral aspect of each corpus cavernosum, one centimeter proximal to the corona. Correct placement was confirmed by fluoroscopic observation of a characteristic spongy pattern after injection of ½ ml. of contrast. Through one needle, intracavernosal pressures were obtained at rest, and then while 100 ml. of 50% diluted contrast medium (-14% iodine) was infused through the second needle. The infusion was begun at the rate of one ml./second, and then increased to two ml./second if IC pressures had not reached 75

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gnme) was mixed v,ith 60 mg. of nanavejrm m 10 ml. of nonheparinized saline, and injected into either corpus cavernosum in one minute. A rubber band was firmly applied around the base of the penis for one minute, and the pharmaceuticals were gently admixed manually within the penis for a few seconds. After 20 minutes, cavernosography was repeated, with filming and pressures as before. The infusion was immediately interrupted if pressures rose over 225 mm. Hg, or if extravasation became evident. The post-infusion pressure responses were most conveniently expressed as a ratio between pressure change and volume infused, dP /dV, called the pressure/volume response (PVR). For example, a PVR of 1 indicated that the IC pressure has risen to 100 mm. Hg after infusion of 100 ml. of fluid. By expressing response as PVR, we were able to distinguish equivalent pressure rises after widely disparate infusion volumes. The PVR (or pressure response), however, can be influenced moderately by a number of irrelevant variables, such as a) rate of infusion of either one ml./second or two ml./second, b) initial capacitance of the corpora cavernosa, and c) the amount of continuing arterial inflow. More refined methods for determin-

mm. Hg after 50 ml. had been infused. were made to stop the infusion had cavemosal pressures reached 225 ml. Hg; this occurred in no case. Radiographs were exposed during infusion, at the rate of one for each 15 ml. infused. The radiographs were obtained in 30 degree posterior oblique projection, with the penis over the ipsilateral thigh. This projection demonstrated the deep penile veins, incompetent perforators, the deep dorsal vein of the penis, and the glans and spongiosum (figs. 1-3). For pharmacocavernosography, one mg. of phentolamine (reTABLE 1.

Procedure performed

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38

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FIG. 1. Diagnosis: normal cavernosogram in 57-year-old sexually active volunteer. A, control cavernosogram. Note abundant venous drainage via veins along undersurface of the shaft, deep dorsal penile vein, drainage into pudenda! plexus (curved arrow), and via internal pudenda! vein (straight arrow). There is also considerable reflux into glans. In this case, other than glans, spongiosa does not opacify appreciably. Note complete opacification of apex of crus. B, twenty minutes after intercavernosal injection of 60 mg. papaverine mixed with one mg. phentolamine, contrast infusion demonstrates erection, and complete absence of venous drainage. Crura tend to appear displaced from ischial ramus (curved arrow) because crura become blind pouches, and cannot fill adequately with contrast agent. C, cavernosometry. Top: minimal pressure rise to 45 mm. Hg after 100 ml. at the rate of one ml./sec. Bottom: abrupt pressure rise to over 225 mm. Hg (monitor demonstrated 305 mm. Hg) after only 40 ml. Arrows along x-axis indicate duration of injection. Pressure was nearly normal 10 minutes after cessation of infusion. However, pressure spontaneously rose again, after withdrawal of needles, and erection did not fully subside for about six hours.

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B FIG. 2. Diagnosis: veno-occlusive incompetence, without venogenic impotence. Single vein with veno-occlusive incompetence in 51-year-old male with 12 months of difficulty with erections. Despite venous leak, pressure response to infusion was normal. At operation, this large perforator was easily identified below Buck's fascia, and stained blue after intracavernosal (IC) administration of methylene blue. After intraoperative IC injection of 30 mg. of papaverine and one mg regitine, pressure rose only to 30 mm. Hg during IC saline infusion at rate of 10 ml./min. After ligating leaking perforator, and re-injection of papaverine, pressure rose to over 100 mm. Hg during IC saline infusion at same rate, and patient developed firm erection. However, impotence did not improve. Indeed, for reasons that remain unexplained after repeat angiography, impotence progressed. A, pharmacocavernosogram after 50 ml. infusion (rate: one ml./sec.) shows good erection, and insignificant opacification of pudenda! plexus (straight arrow), and dorsal vein. Large draining perforator vein is seen (curved arrow), which probably drains via external pudenda! vein (faintly opacified). Note poor opacification of crural apex, indicating good closure of deep penile system. B, pressure response shows prompt rise to estimated level of 235 after 50 ml., for PVR of 4.7. Duration of infusion of 50 ml. is indicated by arrow along xaxis.

774

BOOKSTEIN AND ASSOCIATES

FIG. 3. Diagnosis: venogenic impotence due to veno-occlusive incompetence of deep dorsal penile system. Sixty-nine-year-old male with difficulty maintaining erection. A, control cavernosography demonstrating opacification of deep dorsal vein (hollow arrowhead), internal pudenda! veins (curved arrows), pudenda! plexus (black arrows), external pudenda! vein (straight white arrow) to external iliac system, spongiosa, and ventral circumflex (tortuous arrows). B, after papaverine (60 mg.), pudenda! plexus is almost invisible, and crural apex fails to opacify, indicating closure of deep penile system. There is persistent opacification of deep dorsal penile vein which drains into internal pudenda! veins (large white arrow), and of ventral perforators (tortuous arrow). There is persistent, but reduced opacification of spongiosa. C, pressure response before and after papaverine shows little change, from 30 mm. Hg on control, to 40 mm. Hg after papaverine. One hundred ml. of fluid were infused at rate of two ml./second in interval between arrows.

ing true resistance to venous outflow await further development. Technical caveats, and recent innovations. 1. Puncture of the corpora cavernosa was initially performed via local skin anesthesia at the puncture sites themselves. Regional block from the base of the penis is much better accepted. We suspect, but have not yet conclusively proved, that IC xylocaine is an activator of the veno-occlusive mechanism, and should be avoided to prevent confusion. 2. Cavernosography is associated with a constant risk of contrast extravasation outside the corpus cavernosum, even when proper needle position has been confirmed fluoroscopically. We believe this is usually due to the jet of contrast actually driving the corpus cavernosum off of the needle. We therefore begin the infusion at the rate of one ml./second instead of two, maintaining the volume at 100 ml. We have not yet had extravasation when injection has been at the slower rate. If the pressure response is subnormal, the infusion rate can be raised to two ml./second without interrupting the procedure. The difference in rate of infusion makes little difference in the ultimate pressure obtained. In those patients whose pressures have plateaued at levels of about 30 mm. Hg during infusion at one ml./second, raising the infusion rate to two ml./ second will increase the plateau to about 35 mm. Hg. 3. Constant Ooserv-ation of the penis is mandatory during cavernosography in order to detect extravasation, and halt the infusion at the earliest possible moment. Should extravasation have occurred, the penis becomes quite edematous for a day, but returns to normal afterwards, usually without other sequelae. In one patient, extravasation produced a small skin ulcer. 4. During infusion, cavernosal pressures are not always properly transmitted; the needle can become dislodged, or perhaps a trabeculum can block the needle tip. It is therefore mandatory to observe and palpate the quality of erection, and to warn the patient to report pain, in order to stop the infusion before penile rupture can occur. 5. The initial cavernosogram, that is the non-pharmacologic study, is now commonly omitted. 6. During the early phases of the study, papaverine was sometimes injected without phentolamine. It is our subjective impression that the papaverine-phentolamine mix activates the veno-occlusive mechanism more effectively, and both agents are now administered together. Our incidence of prolonged erection9 has increased since injection of the mixture of agents. 7. Initially, PCG and PCM were performed ten minutes after intracavernosal drug injection. Further experience suggests that twenty minutes is the minimum permissible time delay.

TABLE 2.

Final diagnoses

Normal cavernosal study Arteriogenic impotence alone Venogenic impotence alone Combined vasculogenic impotence

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8. Artificial erection (pharmacologic veno-occlusion and fluid infusion) usually began to subside as soon as the infusion was stopped. Priapism after intracavernosal injection of the papaverine-phentolamine mix is a real risk, however, and one must be prepared to recognize and treat this complication promptly. 9 In this series, priapism developed in one patient, and one normal volunteer. Treatment was instituted after three and eight hours respectively, with prompt response. The treatment consisted of initial cavernosal drainage of about 20 ml. of blood via two 19 gauge or larger needles, followed by intracavernosal injection of 15 micrograms of norepinephrin which was kept in the corpora cavernosa for about five minutes by clamping the drainage tubing. 9. Various drugs may interfere with the erectile process. Patients are encouraged to discontinue smoking and all unnecessary drugs two days before the angiographic examination. RESULTS

Final diagnoses in our 36 impotent patients and two normal volunteers is indicated in table 2. Cavernosometry. The two normal potent volunteers, ages 57 and 61, had baseline cavernosal pressures of seven and 10 mm. Hg. The initial infusions of 100 ml. of fluid (one ml./second in one case, two ml./second in the other) raised intracavernosal pressures to 40 and 45 mm. Hg respectively. After intracavernosal injection of papaverine and phentolamine, and infusion of 40 or 8 ml., pressures rose to 305 and 176 mm. Hg respectively. Pressure/volume responses (PVRs) were therefore 305/ 40 (7.6) and 175/8 (21.9). Both these patients had prolonged effect: one had gradual subsidence of erection over six hours, and the second required treatment for priapism with IC norepinephrin after eight hours. The PVRs of the 36 impotent patients and the two normals who underwent cavernosometry are graphically displayed in figure 4. In the 15 cases with a normal veno-occlusive mechanism that underwent control cavernography (two normal volunteers, eight with non-vasculogenic impotence, and five impotent patients with arteriogenic impotence), the mean control (non-pharmacologic) PVR was 0.91 ± 0.76. In those with a diagnosis of venogenic impotence (alone or in combination)

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that underwent control mean PVR during control was 0.32 normai and abnormal veno-occlusive 1u,cu.1m.1rnrnt nosometry, PVR was 5.47 ± 5.15 in the (n = and 0.36 ± 0.24 (n = 17) in those with abnormal veno-occlusive mechanisms, (p Note in figure 4 that the PVRs in all but two non-pharmacologic studies were below 1.5 (n = 28). In the two with PVR above 1.5, the veno-occlusive mechanism had probably been partially activated by inadvertent intracavernosal injection of xylocaine in one case, and by spinal anesthesia in the other. The non-pharmacologic cavernosograms were not reliable in distinguishing normal from incompetent veno-occlusive mechanisms (columns 1 from 3, fig. 4). After administration of papaverine and phentolamine, the PVRs spread considerably. For reasons given below, those with a pharmacologic PVR above l are considered normal (n = 18); those with a pharma-

5 8

cologic PVR of 1 or below (n = are considered to have venogenic impotence. There was no definition). Isolated venogenic impotence occurred in cases; in eight others, venogenic impotence was combined with arteriogenic. On control cavernosograms, the normal volunteers demonstrated homogenous bilateral opacification of the corpora cavernosa, and variable opacification of the glans and spongiosa (fig, 1A). The crura opacified to their apices. There was abundant venous drainage via the deep dorsal penile veins, the deep penile veins, and perforators (circumflex veins) around and below the shaft of the penis, which appeared to drain primarily into the pudendal plexus and internal pudenda! veins. Occasionally a vein that was interpreted as the external pudendal opacified, and drained via the saphenous. After PCG in the normals, the corpora were enlarged and erect. Flow was completely obstructed in all veins, and to the glans, and spongiosa. Because of obstruction to cmral the crura did not at their apices (fig. and thus appeared to be from the ischial ramus. all the the normal volunteers), demonstrated variable features, which seemed roughly correlated with the PVR. In those with complete ocdusion of all cavernosal venous drainage, ,u,v,,,~,u,, drainage into the glans and spongiosa, was usually, but not always, seen. The cavernosogram occasionally demonstrated moderate venous leak, despite a normal PVR (fig. In patients with progressively diminishing PVRs, persistent drainage via circumflex veins to the dorsal penile, and/or drainage via the deep penile was increasingly evident 3). The combinations of venous leak found in our ua,cn,rn,., venogenic impotence are indicated in table 3. DISCUSSION

It must be emphasized that n,rn:,ce,,.,.,, r,eg:iniintg normal

son1e tients and t·wo normal volunteers has criteria of normal cavernosometry and and without H'''·"""," activation of the veno-occlusive mechanism. ,~;,uu~,HO ~nJ-;n~+r ,.J\lith COIJ.trol cavernosal pressures se,co11wuv to intracavernosal or spinal ,m,,,,,crnsMa, normal cavernosometry under basal conditions was characterized modest elevation of pressure infusion of 100 ml. of at the rnte of one or two ml./ PVR = ,67 ± .39, n = After intracavernosal injection of papaverine and phentolamine, the veno-occlusive mechanism was activated, and marked rise in pressure occurred (mean PVR 5.47 ± 5.15). The PVR was as high as 21 mm. Hg per ml. infused. The control cavernosogram in the two normal volunteers, as well as in other cases considered normal on the basis of pharmacologic pressure response, was generally characterized by free flow into all veins draining the penis, as well as variable flow into the glans and spongiosum. Three venous systems could be identified; the deep dorsal system (circumflex veins, deep dorsal vein, internal pudenda! vein, and occasionally the
776

BOOKSTEIN AND ASSOCIATES

external pudenda! vein); the deep penile system (deep penile veins, pudenda! (pre-prostatic, prostato-vesical, or Santorini's) plexus; the spongiosal system (glans and corpus spongiosum). The deep dorsal system sometimes appeared to drain into the pudenda! plexus, instead of the internal pudenda! vein. After IC papaverine and phentolamine, the degree of obstruction in each of these systems was variable. In patients with PVR above 5.5, little or no leak was seen. Some persistent venous leak was invariably present on cavernosography in patients with PVR under 5. Often one system closed completely, while another system seemed to remain partially or completely patent (figs. 2, 3). The site of leak could not be predicted by any means other than cavernosography. In patients with PVRs between 1 and 3, the pre- and post-pharmacologic cavernosograms were sometimes nearly indistinguishable. In these patients, the degree of veno-occlusive competence was defined only by manometry. Thus both pharmacocavernosometry and pharmacocavernosography were required for accurate evaluation of the overall competence of the venoocclusive mechanism, and the specific sites of incompetence. Our data suggest a continuum of veno-occlusive incompetence, and imply a distinction between veno-occlusive incompetence and venogenic impotence. We believe that veno-occlusive incompetence may or may not be of great clinical import, depending on a balance between severity of leak and inflow capacity of the arterial system. When veno-occlusive incompetence is severe, and PVRs are very low, the leak precludes development of adequate pressures at reasonable arterial inflow, and the diagnosis of venogenic impotence appears clear. However, when veno-occlusive incompetence is minor, then the venous leak may be a contributing factor only, and another dysfunctional element is probably also present. The selection of PVR > 1 as the discriminant between normal and venogenic impotence is based on the following reasoning: 1) in our clinical experience, and that of others,n erection judged subjectively adequate for intromission, and firm enough to lift the penis to >-45 degrees, requires pressure of at least 80, and more usually 100 mm. Hg; 2) in our clinical experience, and that of others, 11 full erection is associated with pressures of 125 mm. Hg or more; 3) average cavernosal blood flow in normals, early in the erectile process during maximal flow, 12- 14 has been measured by xenon clearance to be as high as 60 ml./ min.; 15 4) full erection can develop in normals in well under one minute; 5) therefore, it may be calculated that development

of erection adequate for intercourse (> 100 mm. Hg) well within a period of one minute (volume <60 ml.) would translate into a PVR of> 1.00. Interestingly, conversion of the data of Lue et al. 8 who used a technique similar to ours, indicates that their lower limit of normal PVR would have been 0.8-a figure resembling ours. REFERENCES 1. Puyau, F. A. and Lewis, R.W.: Corpus cavernosography: pressure,

flow, and radiography. Invest. Radiol., 18: 517, 1983. 2. Wespes, E., Delcour, C., Struyven, J. and Schulman, C. C.: Cavernometry-cavernosgraphy; its role in organic impotence. Eur. Urol., 10: 229, 1984. 3. Valji, K. and Bookstein, J. J.: The penile veno-occlusive mechanism of the dog. Angiographic, pharmacologic, and histologic characterization. In preparation. 4. Virag, R., Spencer, P. and Frydman, D.: Artificial erection in diagnosis and treatment of impotence. Urology, 24: 157, 1984.. 5. Virag, R., Frydham, D., Legman, M. and Virag, H.: Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure. Angiology, 35: 79, 1984. 6. Zorgniotti, A. W. and Lefleur, R. X.: Auto-injection of the corpus cavernosum with a vasoactive drug combination for vasculogenci impotence. J. Urol., 133: 39, 1985. 7. Brindley, G. S.: Cavernosal alpha-blockade: a new technique for investigating and treating erectile impotence. Brit. J. Psychiat., 143: 332, 1983. 8. Lue, T. F., Hricak, H., Schmidt, R. A. and Tanagho, E. A.: Functional evaluation of penile veins by cavernosography in papaverine-induced erection. J. Urol., 135: 479, 1986. 9. Virag, G.: About pharmacologically induced prolonged erection. Lancet, 2: 519, 1985. 10. Wespes, E. and Schulman, C. C.: Venous leakage: surgical treatment of a curable cause of impotence. J. Urol., 133: 796, 1985. 11. Michal, V., Simana, J., Rehak, J. and Masin, J.: Haemodynamics of erection in man. Physiologia Bohemoslovaca, 32: 497, 1983. 12. Lue, T., Takamura, T., Schmidt, R. A., Palubinskas, A. J. and Tanagho, E. A.: Hemodynamics of erection in the monkey. J. Urol., 130: 1237, 1983. 13. Anderssen, P-0., Bloom, S. R. and Mellander, S.: Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypepetie. J. Physiol., 350: 209, 1984. 14. Dorr, L. D. and Brody, M. J.: Hemodynamic mechanisms of erection in the canine penis. Am. J. Physiol., 213: 1526, 1967. 15. Shirai, M., Ishii, N., Mitsukawa, S., Matsuda, A. and Nakamura, M.: Hemodynamic mechanism of erection in the human penis. Arch. Androl., 1: 345, 1978.