Daniel Udelson

Mechanisms of Venous Leakage: A Prospective Clinicopathological Correlation of Corporeal Function and Structure

PURPOSE We investigated the pathophysiology of structurally based corporeal veno-occlusive dysfunction. MATERIALS AND METHODS We prospectively evaluated 24 impotent patients (mean age plus or minus standard error 46 +/- 3 years) who had exposure to vascular risk factors and/or disorders inducing diffuse trabecular structure alterations and who underwent penile prosthesis insertion. Preoperative indexes of veno-occlusive function (flow to maintain, venous outflow resistance and pressure decay measurements using repeat dosing pharmacocavernosometry) were correlated with postoperative erectile tissue computer assisted color histomorphometry (percent trabecular smooth muscle to total erectile tissue area). To develop further study findings and correlate histomorphometric findings with molecular biological properties molecular biological studies (ribonuclease protection analysis, reverse transcription-polymerase chain reaction assay for expression of transforming growth factor-beta 1 messenger [m] ribonucleic acid [RNA] and protein affinity labeling techniques for specific transforming growth factor-beta receptors) were performed in representative patients with high (39 to 43%), intermediate (30 to 37%) and low (13 to 29%) trabecular smooth muscle content (normal 42 to 50%). RESULTS Flow to maintain, venous outflow resistance and pressure decay values significantly correlated with trabecular smooth muscle cell content (r = -0.89, 0.82 and -0.85, respectively). In the high, intermediate and low smooth muscle content subgroups flow to maintain, venous outflow resistance and pressure decay values were 1 to 5, 9 to 30 and 50 to 120 ml. per minute, 17 to 84, 3 to 9 and 1 to 2 mm. Hg/ml. per minute, and 40 to 60, 48 to 80 and 110 to 120 mm. Hg decrease in 30 seconds from 150 mm. Hg, respectively. There were no significant differences in patient age or prevalence of risk factors among the 3 subgroups. Patients representative of all 3 subgroups had transforming growth factor-beta 1 mRNA, auto-induction of transforming growth factor-beta 1 mRNA and induction and/or increased availability of all 3 types of transforming growth factor-beta receptors. CONCLUSIONS The pathophysiology of structurally based corporeal veno-occlusive dysfunction is related to elevated corporeal connective tissue content. Based on our data and those in the literature corporeal fibrosis is hypothesized to develop secondary to abnormalities in the regulation of normal collagen synthesis and degradation, most likely associated with adverse influences of chronic ischemia.

Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction

PURPOSE Reliable, clinically available, non-invasive measurements able to predict trabecular histology without the need for erectile tissue biopsy would improve impotence management, since the percentage of trabecular smooth muscle content has been shown to be associated with corporal veno-occlusive dysfunction. The purpose was to identify whether the erectile tissue mechanical property, cavernosal expandability, correlated with the percentage of trabecular smooth muscle content in an animal model of hypercholesterolemia and ischemic-induced corporal fibrosis. MATERIALS AND METHODS New Zealand White rabbits (6 to 7 months old, 3 to 3.5 kg.), were divided into control (n = 7), hypercholesterolemic (n = 5, 0.5% cholesterol diet) and atherosclerotic groups (n = 8, 0.5% cholesterol diet with balloon de-endothelialization). At 16 weeks, the corpora cavernosa were removed en bloc and submerged in physiologic salt solution, and volume-pressure data were plotted at 20 mm. Hg pressure intervals under trabecular smooth muscle relaxation. Cavernosal expandability, X, (the measure of the ability to achieve high corporal expansion at relatively low intracavernosal pressure) and tunical distensibility, V(E)/V(F), (relative volume of fully erect to flaccid penis) were calculated. Erectile tissue was assessed by computer-assisted color histomorphometry with Massons trichrome stained sections (30 to 45 high power fields/animal) to assess percentage of trabecular smooth muscle content. RESULTS The overall mean percentage of trabecular smooth muscle content and mean cavernosal expandability values were 45.4 +/- 1.6, 39.2 +/- 0.9, 33.9 +/- 0.6 and 0.0165 +/- 3.04 x 10(-3), 0.0116 +/- 1.63 x 10(-3), 0.0118 +/- 1.26 x 10(-3) mm. Hg(-1) for the control, hypercholesterolemic and atherosclerotic groups, respectively (r = 0.87). Significant differences in trabecular smooth muscle content were observed among all 3 groups, and in cavernosal expandability, between control and atherosclerotic groups, as well as between control and hypercholesterolemic groups but not between atherosclerotic and hypercholesterolemic groups. CONCLUSIONS The erectile tissue mechanical property, cavernosal expandability, correlated with erectile tissue structural quality. Since cavernosal histology has been shown to predict corporal veno-occlusive function, it is hypothesized that the measurement of cavernosal expandability may become a valuable functional clinical parameter in the diagnosis and treatment of men with erectile dysfunction.

Blunt Trauma: The Pathophysiology of Hemodynamic Injury Leading to Erectile Dysfunction

A 9 1/2-year pharmaco-cavernosometry/pharmaco-cavernosography and pharmaco-arteriography study was performed in 131 men with persistent changes in erectile function following blunt pelvic or perineal trauma. The goal was to determine the incidence of hemodynamic impairment, and to characterize the location and pattern of abnormal venous drainage. Corporeal veno-occlusive dysfunction was identified in 62% of the cases and cavernous artery insufficiency in 70%. Pharmaco-cavernosography revealed abnormal venous drainage confined to the proximal corpora in 91% of the cases. Patients with pelvic trauma had significantly more abnormal sites of venous drainage (3 or more sites in 61%) and more severe degrees to which venous structures filled with contrast medium (23% had 3+ degree of luminal filling) than did patients with perineal trauma (61% had 1 or 2 sites of venous drainage and 92% had 1+ or 2+ degree of luminal filling). Pharmaco-arteriography revealed site specific arterial occlusive lesions consistent with the site of impact. Traumatic vasculogenic impotence is hypothesized as being the result of direct impact injury to the fixed proximal corpora and its arterial inflow bed. The exerted perineal impact force is estimated to range from 50 to 500 pounds, depending on the weight of the individual, height of the fall, speed at contact and surface hardness. Traumatic veno-occlusive dysfunction is theorized to be the consequence of focal intracavernous wound repair and permanent focal alterations in erectile tissue compliance. Traumatic vasculogenic impotence afflicts an estimated 600,000 American men of whom 250,000 have sports-related injuries. Future consideration should be given to the development of appropriate protective perineal equipment.

In Vivo Assessment of Trabecular Smooth Muscle Tone, its Application in Pharmaco-Cavernosometry and Analysis of Intracavernous Pressure Determinants

A pharmaco-cavernosometry based clinical study was designed to define hemodynamic parameters consistent with complete trabecular smooth muscle relaxation, establish a methodology for overcoming incomplete trabecular smooth muscle relaxation, and determine under controlled conditions the contribution of venous outflow and arterial inflow to the steady-state equilibrium intracavernous pressure. Flow-pressure relationships were analyzed in 21 patients each of whom was assumed to have complete smooth muscle relaxation by virtue of the full, rigid and maintained erectile response following intracavernous vasodilator administration, which required intracavernous adrenergic agonists to achieve detumescence. Flow-to-maintain values increased linearly with intracavernous pressure while venous outflow resistance values were high and constant. Based on these relationships, trabecular smooth muscle tone was assessed in 123 impotent patients. In 14%, 63% and 14% of the patients (112 of 123 overall), respectively, 1, 2 and 3 doses of vasoactive agents were required to achieve hemodynamic relationships consistent with complete trabecular smooth muscle relaxation. In 9% of the patients such hemodynamic relationships were unable to be reached. In the 112 patients the influence of different engineering based measures of corporeal veno-occlusive function, including flow-to-maintain, pressure decay, venous outflow resistance and corporeal capacitance, was analyzed against the spectrum of equilibrium steady-state intracavernous pressures. Two distinct equilibrium pressure groups were identified reflecting different capacitance states: pressures greater than 60 mm. Hg (associated with low capacitance values) and pressures less than 50 mm. Hg (associated with high capacitance values), with pressures 50 to 59 mm. Hg representing a hemodynamic transition zone. When analyzed during complete trabecular smooth muscle relaxation, corporeal veno-occlusive hemodynamic variables in conjunction with cavernous arterial perfusion pressure determine the steady-state equilibrium intracavernous pressure. Failure to assess corporeal veno-occlusive function under such conditions will overestimate the degree of suspected corporeal structural disease.

Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part II—Clinical implications of penile buckling

Purpose: Penile buckling force was analytically described in terms of its constituents. In addition, theoretically-derived buckling force data were compared to clinically measured data and the influence of each constituent on penile buckling force data was assessed.Methods: Using engineering buckling theory for a column, a mathematically-derived penile buckling model was developed which incorporated geometric and hemodynamic data obtained by dynamic infusion pharmacocavernosometry studies in 21 impotent patients (age 43, range 24–62 y) as well as penile tissue mechanical characteristics previously developed (Part I).Results: In 17 of 21 patients the mean difference between theoretically derived and clinically measured buckling force data was 0.33±0.25 kg (r=0.96). Factors which increased penile buckling forces were: high intracavernosal pressure values (rigidity was related to pressure in an exponential-like fashion); high penile aspect ratio (D/L) values (relatively large diameter/short length penile geometry) and high flaccid diameter; and high cavernosal expandability values (a measure of the ability of the corpora to approach its erect volume with relatively low intracavernosal pressures).Conclusions: Pressure-volume data (pressure, geometry and tissue characteristics) obtained during erectile function testing have been shown, for the first time, to theoretically predict the magnitude of clinically-measured penile buckling forces.

Engineering analysis of penile hemodynamic and structural- dynamic relationships: Part I—Clinical implications of penile tissue mechanical properties

Purpose: The least investigated physical determinant of penile rigidity has been penile tissue material properties. The goals in this study (Part I) were to define two penile mechanical parameters, cavernosal expandability X and tunical distensibility VE/VF, determine their magnitudes in humans and develop an analytical expression for penile volume as a function of these two tissue characteristics and intracavernosal pressure.Methods: Dynamic infusion pharmacocavernosometry was performed in 21 impotent patients (age 43±19 y) to provide human geometric, hemodynamic and structural data. A mathematically derived model of hemodynamic and structural-dynamic characteristics of penile erection was developed (Parts I, II, III) incorporating penile tissue mechanical qualities.Results: Cavernosal expandability X provided a measure of the ability to approach maximum volume at relatively low intracavernosal pressures. Tunical distensibility VE/VF denoted the maximal erect to flaccid penile volume ratio. The magnitudes of X and VE/VF in the study population were 0.04–0.17 mmHg−1 and 1.7–5.0 respectively.Conclusions: Enabling penile volume to be derived as a function of tissue mechanical characteristics and pressure, allows for penile rigidity to be expressed (in Part II) as a function of pressure, geometry and tissue qualities.

Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part III—Clinical considerations of penile hemodynamic and rigidity erectile responses

Purpose: The extent to which hemodynamic erectile responses predict penile buckling forces has not previously been analytically investigated. An engineering study was performed to compare hemodynamic data with penile buckling force values.Methods: Dynamic infusion pharmacocavernosometry studies in 21 impotent patients (age 43, range 24–62 y) were accomplished to obtain information during penile erection concerning hemodynamic values, penile buckling forces and their determinants: intracavernosal pressure, erectile tissue mechanical properties and penile geometry.Results: In the 21 patients, discrepancies existed in several patients who demonstrated normal hemodynamic values (low flow-to-maintain and high equilibrium intracavernosal pressures) but elevated cavernosal compliance values and diminished penile buckling forces. There was poor correlation between cavernosal compliance and equilibrium intracavernosal pressure (r=−0.36); better correlation between compliance and expandability (r=−0.72) and best correlation between dimensionless compliance and the dimensionless product of expandability with equilibrium pressure (r=−0.88). These data implied that cavernosal compliance was dependent on multiple factors, not only equilibrium intracavernosal pressure.Conclusions: Hemodynamic indices which correlate with intracavernosal pressure alone do not predict penile buckling forces since the latter are dependent not only on intracavernosal pressure but also on penile geometry and erectile tissue properties. The most relevant tissue property in predicting adequate penile buckling forces is cavernosal expandability. A new impotence classification system and diagnostic algorithm based on the determinants of penile rigidity and not exclusively on hemodynamic responses is proposed.

A Guide to Safe Corporotomy Incisions in the Presence of Underlying Inflatable Penile Cylinders: Results of In Vitro and In Vivo Studies

PURPOSE Because iatrogenic injury to an underlying inflatable implant may be induced by electrocautery incision of the tunica during tunical release or cylinder reexploration, safe electrocautery guidelines are needed. MATERIALS AND METHODS For the in vitro model silicone and polyurethane elastomer lined inflatable penile prosthetic cylinders were used, and cutting and coagulation electrocautery was applied directly on the device, on a tissue-implant interface, and at minimal, partial or full inflation with saline. For the in vivo study 10 patients with underlying inflatable prosthetic cylinders underwent tunical releases for treatment of secondary penile curvature (7) and reexploration for a malpositioned device (3) with a minimum 1 year of followup. RESULTS In the in vitro study electrocautery injuries either did not occur when applied directly to silicone and polyurethane elastomer lined devices, occurred in both devices in the presence of a tissue-implant interface, occurred in polyurethane elastomer lined devices at a far less thermal energy setting than with silicone, occurred in both implants at lower wattages with increasing saline inflation or did not occur in 100% of polyurethane elastomer lined devices when coagulation electrocautery was less than 65 watts. In the in vivo study, by adhering to the aforementioned principles and using novel surgical techniques, no device malfunctions were created intraoperatively or observed within a mean followup of 22 months. CONCLUSIONS Electrocautery can be used safely to create a tunical incision with any underlying inflatable cylinder. To avoid electrocautery injury, based on the clinical study results in polyurethane elastomer lined devices, one should deflate the cylinder before electrocautery, use coagulation current at 35 watts, apply the electrocautery only to the outer longitudinal tunical layer, bluntly dissect through the inner circular layer, and elevate the tunica, protect the device and incise the tissue under direct vision.

VACUUM ERECTION ASSOCIATED IMPOTENCE AND PEYRONIE'S DISEASE

PURPOSE Use of a nonmedical, catalogue type vacuum erection device resulted in a case of vacuum induced vasculogenic impotence and Peyronies disease. MATERIALS AND METHODS A 66-year-old potent man used a nonmedical vacuum erection device (cylinder plus a hand pump without a pressure-release valve and a doughnut-shaped ring at the base without tension bands) after having achieved a spontaneous rigid erection. The resultant excessive overinflation of the penis was followed by dorsal curvature, diminished rigidity and decreased erectile maintenance. RESULTS Physical examination revealed a dorsal mid shaft Peyronies plaque. Nocturnal penile tumescence testing and office injection testing were abnormal and demonstrated partial, short-lived, dorsally curved erections. Dynamic pharmaco-cavernosometry and pharmaco-cavernosography established vasculogenic impotence with site-specific crural (unrelated to the Peyronies plaque) veno-occlusive dysfunction and dorsal penile curvature. CONCLUSIONS Vacuum erection devices create pulling forces on the penis. We estimate that the pulling forces in this case were prohibitively high (approximately 29 pounds) due to absence of a pressure-release valve and to the preexistent erection at vacuum application. These intense pulling forces are hypothesized to have damaged the tunica in the mid shaft (Peyronies disease) and the crus (veno-occlusive dysfunction), the latter being the site of attachment of the corpora to the ischiopubic ramus and a most likely location for high magnitude pulling forces to exert an abnormal injury effect. The patient underwent a Nesbit plication procedure and presently performs self-injection for satisfactory sexual activity.

Biomechanics of male erectile function.

Two major branches of engineering mechanics are fluid mechanics and structural mechanics, with many practical problems involving the effect of the first on the second. An example is the design of an aircrafts wings to bend within reasonable limits without breaking under the action of lift forces exerted by the air flowing over them; another is the maintenance of the structural integrity of a dam designed to hold back a water reservoir which would exert very large forces on it. Similarly, fluid and structural mechanics are involved in the engineering analysis of erectile function: it is the hydraulic action of increased blood flow into the corpora cavernosa that creates the structural rigidity necessary to prevent collapse of the penile column.