Chronic ischemia alters prostate structure and reactivity in rabbits.

PURPOSE: Autopsy studies performed in men older than 80 years old have demonstrated that 90% have histological evidence of benign prostatic hyperplasia. Despite this fact pressure flow studies in men of this age who are referred for the evaluation of lower urinary tract symptoms have shown that only 40% have evidence of bladder outlet obstruction. To our knowledge the specific features of benign prostatic hyperplasia responsible for bladder outlet obstruction are not known. To investigate the possible etiological factors responsible for bladder outlet obstruction we determined whether chronic ischemia alters the structural and functional properties of the prostate. MATERIALS AND METHODS: Male New Zealand White rabbits weighing 3.5 to 4 kg. were divided into a chronic prostate ischemia (12), hypercholesterolemia (8) and age matched control (8) group. The chronic prostate ischemia group underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet, the hypercholesterolemia group received a 0.5% cholesterol diet only and controls received a regular diet. After 12 weeks using anesthesia iliac artery and prostatic blood flow was measured by an ultrasonic and laser Doppler flowmeter, respectively. The animals were then sacrificed and the prostate was processed for histological evaluation, immunohistochemical staining for vascular endothelial growth factor expression and organ bath studies. RESULTS: Iliac artery and prostatic blood flow was significantly decreased in the chronic prostate ischemia compared with the hypercholesterolemia and control groups. Histological findings included thickening and fibrosis of the prostatic stroma and cystic atrophy of the epithelium in the chronic prostate ischemia group as well as minor thickening of the stroma in the hypercholesterolemia group. These structural changes correlated with decreased vascular endothelial growth factor expression. Organ bath studies showed that chronic ischemia and to a lesser extent hypercholesterolemia impaired electrical field stimulation induced neurogenic relaxation of the prostatic tissue. Neurogenic relaxation of the prostatic tissue was improved by combined treatment with indomethacin and L-arginine in the hypercholesterolemia but not in the chronic prostate ischemia group. Nitric oxide donor sodium nitroprusside produced comparable relaxation in all 3 groups. CONCLUSIONS: Chronic ischemia causes marked changes in prostatic structure and contractility. Ischemia induced glandular atrophy was consistently associated with decreased vascular endothelial growth factor expression. Decreased relaxation of the ischemic tissue to electrical field stimulation appears to involve the nitric oxide pathway. The nitric oxide precursor L-arginine reversed hypercholesterolemia induced impairment of prostatic tissue relaxation. Our study suggests that chronic ischemia results in thickening and fibrosis of the prostate, changing its mechanical properties. Chronic ischemia also impairs neurogenic relaxation in the prostate. We discuss the possible relationship of these changes to clinical bladder outlet obstruction.

Urinary incontinence after treatment for localized prostate cancer.

The incidence of incontinence after radical prostatectomy has ranged from 0 to 57% depending on the series and the type of incontinence considered. When total incontinence (not minimal stress incontinence) is reported, the average incidence is no more than 5%. This figure will increase with age, and in most series, approximately 10% of patients around the age of 70 will have total incontinence postoperatively. Preservation of continence after radical prostatectomy depends largely on the preservation of the distal urethral smooth-muscle sphincteric mechanism, which begins at the pelvic floor and ends at the prostatourethral junction. Newer techniques that attempt to increase postoperative continence include not cutting the puboprostatic ligaments and attempting to preserve as much striated muscle as possible along the length of the remaining urethra. Patients who are incontinent for 6 months after the surgery with no evidence of improvement will probably not become continent on their own. Therefore, some type of therapy should be considered. The options are periurethral injection of a bulking agent, implantation of an artificial sphincter, and, most recently, a bulbourethral sling procedure.

Atherosclerosis-induced chronic arterial insufficiency causes clitoral cavernosal fibrosis in the rabbit.

In our previous studies we found that aging-associated fibrosis of clitoral cavernosal tissue correlated with the prevalence of cardiovascular disease in elderly women. The aim of this study was to determine specifically, arterial insufficiency-related structural changes of clitoral cavernosal tissue in a rabbit model. New Zealand white female rabbits were divided into clitoral cavernosal ischemia (CCI, n = 5) and control (n = 5) groups. The CCI group underwent balloon endothelial injury of the iliac arteries and received 0.5% cholesterol diet. The control group received a regular diet. After 16 weeks, arteriography was performed then the animals were sacrificed. The iliac arteries and the entire clitoris were removed. Cross-sections of the iliac arteries and clitoris were processed for histologic evaluation The percentage of smooth muscle and connective tissue in trichrome stained sections of clitoral cavernosal tissue was determined by computer-assisted histomorphometry. Arteriography revealed diffused occlusive disease in the common iliac, internal iliac and pudendal arteries in the CCI group. Histology showed that arterial occlusive disease spreads from the site of balloon injury to the smaller branches involving the clitoral cavernosal arteries. Diffuse fibrosis was observed in the clitoral cross-sections of the CCI group. The percentage of clitoral cavernosal smooth muscle (mean +/- standard error) in the CCI group (53% +/- 0.9%) was significantly decreased compared with the control group (62% +/- 0.8%) (P = 0.0001). Chronic clitoral cavernosal ischemia causes significant fibrosis and loss of smooth muscle in the clitoral cavernosal tissue. These findings suggest that chronic clitoral cavernosal arterial insufficiency may play a role in the pathophysiology of female sexual arousal disorders.

Isoprostane 8-epi PGF2alpha, a product of oxidative stress, is synthesized in the bladder and causes detrusor smooth muscle contraction.

Isoprostane 8-epi PGF2alpha is a product of oxidative stress that causes potent smooth muscle contraction. Its production increases in conditions associated with oxidative stress such as in diabetes, smoking, and aging. The aim was to study whether the urinary bladder synthesizes isoprostane 8-epi PGF2alpha and releases to the urine and whether isoprostane 8-epi PGF2alpha causes bladder smooth muscle contraction. Urine samples were obtained transurethrally from 12 male New Zealand white rabbits for measurement of isoprostane 8-epi PGF2alpha levels. To examine whether bladder synthesizes isoprostane 8-epi PGF2alpha, both ureters were ligated, then the bladder was washed 5 times by filling and emptying with normal saline. Bladder was refilled with normal saline, and at 5 minutes a bladder washout sample was taken. After this, the bladder was contracted by nerve stimulation periodically for 30 minutes, and then another washout sample was taken. Strips of bladder tissues were processed for study of isoprostane 8-epi PGF2alpha production in tissue culture chambers and for isometric tension measurements in the organ bath. Enzyme immunoassay (EIA) revealed a remarkable amount of isoprostane 8-epi PGF2alpha in the rabbit urine. EIA of washout samples showed that the bladder synthesizes isoprostane 8-epi PGF2alpha and its production increases with nerve stimulation-induced contractions. EIA of samples from the tissue culture media showed that bladder strips synthesize isoprostane 8-epi PGF2alpha in vitro. Electrical field stimulation (EFS) significantly increased the synthesis and release of isoprostane 8-epi PGF2alpha by the bladder strips. In the organ bath, isoprostane 8-epi PGF2alpha caused concentration-dependent contraction of bladder tissue. While the threshold contraction required smaller concentration of isoprostane 8-epi PGF2alpha (3 nmol) than carbachol (10 nmol), the amplitude of contraction to carbachol was greater than isoprostane 8-epi PGF2alpha. Our studies show that the rabbit bladder synthesizes isoprostane 8-epi PGF2alpha and releases it to the urine. Production of isoprostane 8-epi PGF2alpha in the bladder increases with nerve stimulation-induced contraction. Exogenous isoprostane 8-epi PGF2alpha causes significant bladder smooth muscle contraction. Our findings necessitate further studies to evaluate the possible role of oxidative stress and increased isoprostane 8-epi PGF2alpha production in bladder dysfunction. Neurourol. Urodynam. 19:43-51, 2000.

Current concepts and controversies in urodynamics.

Urodynamics is the dynamic study of the transport, storage, and evacuation of urine by the urinary tract. It is comprised of several tests that, when used individually or collectively, can give information about lower urinary tract function. The components of the urodynamic study are uroflowmetry, cystometry, pressure-flow studies, electromyography, urethral pressure profilometry, leak point pressure measurement, videourodynamics, and ambulatory urodynamics. Familiarity with the recent advances and controversies of each component is essential when using urodynamics to diagnose and treat lower urinary tract dysfunction.

Overactivity and structural changes in the chronically ischemic bladder.

PURPOSE: Our aim was to study the effect of chronic ischemia on bladder contraction and detrusor smooth muscle reactivity. The relationship between structural damage and functional changes in the chronically ischemic bladder was also investigated. MATERIAL AND METHODS: Male New Zealand White rabbits were divided into arterial injury (AI), hypercholesterolemia (Hch) and control groups. The AI group (n = 18) underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet. The Hch group (n = 8) received a 0.5% cholesterol diet alone. The control group (n = 8) received a regular diet. After 16 weeks, iliac artery and bladder wall blood flows were recorded. Cystometrograms and arteriography were obtained and bladder tissues were processed for isometric tension measurement in the organ bath and for histological evaluation. RESULTS: At 16 weeks, blood flow through the iliac arteries was significantly reduced in the AI group compared with the Hch and control groups. In the AI group, 8 animals developed severe bladder ischemia (SBI) defined as greater than 60% decrease in bladder blood flow, 7 animals developed moderate bladder ischemia (MBI) defined as 40 to 60% decrease in bladder blood flow, and 3 animals failed to develop significant bladder ischemia (<40% decrease in bladder blood flow). In the control animals, bladder blood flow increased prior to contraction, decreased during contraction and rebounded to baseline levels after contraction. In animals with MBI and SBI, the increase in bladder blood flow prior to contraction and the rebound of blood flow after contraction, both seen in control animals, were diminished. Detrusor overactivity (significant increase in the frequency of spontaneous bladder contractions) was observed in the MBI group and impaired bladder contraction in the SBI group. In the organ bath, bladder strips from the MBI group demonstrated increased contractile response to carbachol and electrical field stimulation (EFS) while bladder strips from the SBI group showed impaired contractility. Hch alone produced only short-lived ischemia during bladder contraction and caused significantly lesser functional changes compared with those seen in MBI. Histological examination showed atherosclerotic occlusion in the iliac arteries and bladder microcirculation and marked disruption of urothelium in the MBI and SBI groups. Severe fibrosis was seen in bladder tissue from the SBI group, moderate fibrosis in tissue from the MBI group and mild fibrosis in tissue from the Hch group. CONCLUSIONS: Our studies show that chronic MBI is associated with detrusor overactivity and increased smooth muscle contractility to carbachol and EFS while chronic SBI is associated with impaired detrusor contraction. The mechanism of chronic ischemia-induced bladder dysfunction is not known and may involve multiple physiologic and structural changes in the bladder nerves, receptors and contractile components. Our studies suggest that ischemia-induced structural damage in the urothelium and possible chronic exposure of the underlying tissue and nerves to the urine may also play a role in MBI-induced detrusor overactivity. SBI-induced impairment of bladder contraction may involve, in part, extensive fibrosis and loss of bladder smooth muscle. Histopathophysiologic changes in bladder tissue from our MBI model are similar to those seen in patients with detrusor instability, suggesting that chronic ischemia may play a role in the development of idiopathic detrusor instability.

The causes of patient dropout from penile self-injection therapy for impotence.

PURPOSE: Penile self-injection therapy, a second line treatment for erectile dysfunction, is the most efficacious means of reestablishing functional erections when first line therapies fail and the patient wants to avoid penile prosthesis implantation. Despite high efficacy rates, injection therapy has high dropout rates. To our knowledge studies to date analyzing patient attrition have reviewed small numbers of patients followed for only short periods. We elucidate the main reasons for patient dropout in a large penile self-injection program with long-term followup. MATERIALS AND METHODS: A questionnaire was mailed to 1,424 patients who completed the office training and home use phases of a penile self-injection program. RESULTS: The overall attrition rate was 31% of the 720 men who completed the questionnaire, with a mean followup of 38 months. The main reasons for dropout were cost of therapy, patient and partner problems with the concept of penile injection, lack of partner availability and spontaneous improvement in erections. Lack of efficacy of therapy was the primary reason for only 1 of 7 dropouts. Furthermore, adverse effects of penile injections (priapism, penile nodules, pain) appeared to be only minor contributors to dropout. CONCLUSIONS: To our knowledge this study is the largest published, single center cohort of patients treated with injection and followed for an analysis of dropout rates. Based on study data a reduction in dropout rates may be achieved by keeping the cost of therapy low, and ensuring patient and partner education as well as continued support throughout treatment.

The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences.

OBJECTIVES: To project the likely worldwide increase in the prevalence of erectile dysfunction (ED) over the next 25 years, and to identify and discuss some possible health-policy consequences using the recent developments in the UK as a case study. METHODS: Using the United Nations projected male population distributions by quinquennial age groups for 2025, the prevalence rates for ED were applied from the Massachusetts Male Aging Study (MMAS) to calculate the likely incidence of ED. The MMAS has the advantage of being the first study to provide population-based rates rather than rates based on clinical samples. All the projections were age-adjusted. RESULTS: It is estimated that in 1995 there were over 152 million men worldwide who experienced ED; the projections for 2025 show a prevalence of approximately 322 million with ED, an increase of nearly 170 million men. The largest projected increases were in the developing world, i.e. Africa, Asia and South America. DISCUSSION: The likely worldwide increase in the prevalence of ED (associated with rapidly ageing populations) combined with newly available and highly publicized medical treatments, will raise challenging policy issues in nearly all countries. Already under-funded national health systems will be confronted with unanticipated resource requests and challenges to existing government funding priorities. The projected trends represent a serious challenge for healthcare policy makers to develop and implement policies to prevent or alleviate ED.

Transforming growth factor-beta1 (TGF-beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo.

PURPOSE: The pleotropic cytokine TGF-beta1 which induces connective tissue synthesis, and inhibits the growth of smooth muscle cells, has been implicated in corpus cavernosum fibrosis. The objective of this study was to determine the dose and time dependence of TGF-beta1 as an active agent in penile corporal fibrosis in an animal model. MATERIALS AND METHODS: A time release method of delivery was developed using sodium alginate microspheres containing recombinant human (rh) TGF-beta1. New Zealand White rabbits were injected intracorporally with a single alginate microsphere either with or without rh-TGF-beta1. Dosage was varied from 325 to 1500 ng./bead. Animals were sacrificed at either three or five days post injection and the penises removed en bloc, examined, and processed for quantitative histomorphometric analysis, staining the sections with Masson's trichrome. RESULTS: Alginate microspheres containing [125I]-rh-TGF-beta1 showed slow-release kinetics (t1/2 = 10.5 hours). Histomorphometric analysis of 60 sets of high powered fields/treatment/ animal showed dose dependent decreases in percentage of corporal smooth muscle with TGF-beta1 treatment (750 to 1500 ng./bead). Placebo (alginate microspheres alone) had trabecular smooth muscle content comparable to values previously reported for untreated rabbit corpus cavernosum. CONCLUSIONS: This study confirms that TGF-beta1 induces fibrosis in situ by altering connective tissue synthesis and hence the structure of the corpus cavernosum. Injection of rh-TGF-beta1 impregnated alginate microspheres into the corpus cavernosum resulted in dose-dependent decreases in percentage of corporal smooth muscle.

Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non-compliance in the rabbit.

PURPOSE: The overall goal was to determine whether chronic ischemia and hypercholesterolemia interfere with bladder function and structure. The roles of atherosclerosis-induced chronic ischemia and hypercholesterolemia in bladder fibrosis and non-compliance were studied in the rabbit. The relationship between ischemia-induced changes in the expression of transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) and the severity of bladder fibrosis was also investigated. MATERIALS AND METHODS: Male New Zealand White rabbits were divided into chronic bladder ischemia (CBI, n = 11), hypercholesterolemia (Hch, n = 8) and control (n = 8) groups. The CBI group underwent balloon endothelial injury of the iliac arteries and received a 0.5% cholesterol diet. The Hch group received a 0.5% cholesterol diet alone. The control group was placed on a regular diet. After 16 weeks, iliac artery and bladder wall blood flow measurements, cystometrograms (CMG) and aorto-iliac arteriograms were obtained in all animals. Iliac arteries and bladder tissues were processed for histological staining and computer-assisted histomorphometric image analysis. The expressions of TGF-beta1 and bFGF in bladder tissue were determined by immunohistochemical staining utilizing monoclonal antibodies. RESULTS: At 16 weeks, arteriography and histology showed significant diffuse atherosclerotic occlusive disease of the aorto-iliac arteries in the CBI group. Iliac artery and bladder wall blood flows were significantly decreased in the CBI group compared with the Hch and control groups. Atherosclerosis-induced CBI shifted the volume-pressure curve to the left and caused severe bladder fibrosis. Hypercholesterolemia also caused fibrosis and non-compliance but to a much lesser extent compared with those caused by CBI. In histomorphometry, the percentage of detrusor smooth muscle was moderately decreased in the Hch group and severely decreased in the CBI group compared with the control group. In immunohistochemical stains of bladder tissues, bFGF expression was similar in the three groups of animals. TGF-beta1 expression was significantly greater in bladder tissues from the CBI group compared with the Hch and control groups. CONCLUSIONS: Our studies show that atherosclerosis-induced chronic ischemia increases TGF-beta1 expression in the bladder leading to fibrosis, smooth muscle atrophy and non-compliance. Hypercholesterolemia also interferes with bladder structure and compliance but to a significantly lesser extent compared with CBI. Our studies suggest that arterial insufficiency and hypercholesterolemia, common aging-associated disorders, may play important roles in the pathophysiology of voiding dysfunction in the elderly.

Relative roles of cyclooxygenase and nitric oxide synthase pathways in ischemia-induced increased contraction of cavernosal smooth muscle.

PURPOSE: To study the mechanism of chronic ischemia-induced increased cavernosal smooth muscle contraction in an animal model of vasculogenic erectile dysfunction. MATERIALS AND METHODS: New Zealand White rabbits were divided into control (n = 6, fed with a regular diet), hypercholesterolemic (n = 9, fed with a diet containing 0.5% cholesterol) and chronic cavernosal ischemia (CCI, n = 10, underwent balloon de-endothelialization of iliac arteries and received a diet containing 0.5% cholesterol) groups. After 16 weeks, the relationship between iliac artery blood flow and cavernosal smooth muscle contraction was studied. The roles of cyclooxygenase and nitric oxide (NO) pathways in chronic ischemia-induced increased smooth muscle contraction were also examined. RESULTS: Iliac artery blood flow in the CCI group was significantly reduced compared with the control and hypercholesterolemic groups. Hypercholesterolemia alone did not affect cavernosal smooth muscle contraction. Atherosclerosis-induced chronic cavernosal arterial insufficiency did not affect contraction to norepinephrine while causing a significant increase in electrical field stimulation-induced neurogenic contraction. Inhibition of the cyclooxygenase pathway by indomethacin decreased electrical field stimulation-induced contraction in all animals but failed to normalize the differences between CCI and control groups. In the presence of indomethacin, L-arginine decreased electrical field stimulation-induced contraction in the control and hypercholesterolemic groups but not in the CCI group. In the presence of indomethacin, treatment with nitric oxide synthase (NOS) inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), increased electrical field stimulation-induced contraction in all groups. This effect of L-NMMA on smooth muscle contraction was significantly greater in the control and hypercholesterolemic groups compared with the CCI group. After tissue treatment with L-NMMA, the magnitude of contraction in cavernosal tissue from control and hypercholesterolemic groups was similar to those observed in the CCI group. CONCLUSIONS: Mechanism of chronic ischemia-induced increased cavernosal smooth muscle contraction involves increased output of constrictor eicosanoids and impairment of the inhibitory influence of NO pathway in cavernosal tissue.

Histomorphometric analysis of age-related structural changes in human clitoral cavernosal tissue.

PURPOSE: To characterize age-associated histological changes of human clitoral cavernosal tissue and to determine whether age-related histological changes of clitoral cavernosal tissue correlate with vascular disease-related mortality. MATERIALS AND METHODS: Human clitorises were obtained from 15 fresh cadavers (age: 11 to 90 years) and from 3 patients undergoing clitoral surgery (age: 6 months to 15 years). Cross sections of the clitorises were stained with Masson's trichrome and utilized for computer assisted histomorphometric image analysis to determine the clitoral cavernosal content of smooth muscle and connective tissue. RESULTS: These studies revealed a strong link between increase in age and decreased clitoral cavernosal smooth muscle fibers. In histomorphometry, the percentage of clitoral cavernosal smooth muscle (mean +/- standard error) in an age group of 6 months to 15 years (n = 4) was 65+/-1.5, in 44 to 54 years (n = 7) was 50+/-1.2, and in 55 to 90 years (n = 7) was 37+/-1.3 (ANOVA, p = 0.0001). In the 18 tissues studied, decrease in the percentage of clitoral cavernosal smooth muscle significantly correlated with increase in age (simple regression, r = 0.61). In the age group of 44 to 90 years, clitoral cavernosal fibrosis was significantly greater in the presence of cardiovascular disease-related mortality compared with those without cardiovascular disease-related mortality. CONCLUSION: This study shows that aging women undergo histological changes in clitoral cavernosal erectile tissue. Vascular risk factors may adversely affect the structure of clitoral cavernosal tissue. These findings may be of importance in the pathophysiology of age-associated female sexual arousal disorders.

Axial penile buckling forces vs Rigiscan radial rigidity as a function of intracavernosal pressure: why Rigiscan does not predict functional erections in individual patients.

AIM: An improved understanding of the relationship between radial and axial rigdity values would enable better appreciation of the clinical usefulness of RigiScantrade mark, the most widely utilized determination of erectile rigidity testing. Previous studies have shown that axial rigidity (measured by buckling forces) correlated well with radial rigidity (measured by RigiScantrade mark) for radial rigidity values below 60%. For radial rigidity exceeding 60%, there was poor correlation. Heretofore, there has been no physiologic explanation of this phenomenon. METHODS: During dynamic pharmacocavernosometry in 36 impotent patients, we investigated the relationship between axial buckling forces and RigiScan radial rigidity and, for the first time, how they both vary with pressure, (which we varied over over a wide functional range). In addition, we recorded multiple penile length and diameter values enabling us to relate, also for the first time, axial and radial rigidity to individual mechanical erectile tissue and penile geometric properties. RESULTS: Marked differences were found in the manner RigiScan radial rigidity units and axial buckling force magnitudes increased with increases in intracavernosal pressure values in each individual. The former asymptotically approached a maximum finite value while the latter increased continuously towards infinity. Based on data in this study, RigiScan radial rigidity values greater than 55% may be considered a necessary criteria for vaginal intromission capability in all partners but it is not a sufficient one. CONCLUSIONS: Axial and radial rigidity share a common dependency upon intracavernosal pressure, however, they are also dependent upon other unique physical determinants. For axial rigidity, additional dependent variables include cavernosal erectile tissue properties and penile geometry, while for radial rigidity, this may include tunical surface wall tension properties. Clinical devices which assess functional penile rigidity should utilize axial and not radial rigidity testing.

Mechanisms of ischemia-induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction.

PURPOSE: To determine the effects of hypercholesterolemia and atherosclerosis-induced chronic cavernosal arterial insufficiency on cavernosal smooth muscle tone, nitric oxide synthase (NOS) activity and cavernosal tissue synthesis of constrictor eicosanoids. To study whether inhibition of the cyclooxygenase pathway by indomethacin and tissue treatment with nitric oxide (NO) precursor L-arginine improve hypercholesterolemia and ischemia-induced impaired endothelium-dependent and neurogenic relaxation of cavernosal tissue. MATERIALS AND METHODS: New Zealand White rabbits were divided into control (n = 10, fed a regular diet), hypercholesterolemia (Hch, n = 13, fed a diet containing 0.5% cholesterol) and chronic cavernosal ischemia (CCI, n = 14) groups. The CCI group underwent balloon deendothelialization of iliac arteries and received a diet containing 0.5% cholesterol. After 16 weeks, we examined the effects of Hch and balloon de-endothelialization induced arterial occlusive disease on iliac arterial blood flow, reactivity of cavernosal tissue, cavernosal NOS activity and cavernosal tissue synthesis of constrictor eicosanoids. RESULTS: Histology revealed significant atherosclerotic arterial occlusive disease in the CCI group. Iliac artery blood flow in the CCI group was significantly reduced compared with the control and Hch groups. In the Hch and CCI groups, endothelium-dependent relaxation of cavernosal tissue to acetylcholine was significantly reduced compared with the control group. Electrical field stimulation-induced neurogenic relaxation and cavernosal NOS activity were significantly reduced in the CCI group but not in the Hch group. The basal release of cavernosal constrictor eicosanoids, prostaglandin F2alpha (PGF2alpha) and thromboxane A2 (TXA2) was significantly increased in the CCI group. Indomethacin increased endothelium-dependent relaxation in all groups and neurogenic relaxation in the CCI group, but failed to normalize the differences in relaxation between treated and control groups. In the presence of indomethacin, L-arginine improved endothelium-dependent relaxation of cavernosal tissue in the Hch group but did not normalize endothelium-dependent or neurogenic relaxations in the CCI group. Relaxation to NO donor sodium nitroprusside and papaverine was similar in cavernosal tissue from all groups. CONCLUSIONS: Impairment of endothelium-dependent relaxation by Hch occurs secondary to disruption of the NO formation in cavernosal endothelium. Improvement of endothelium-dependent relaxation by L-arginine may suggest lack of availability of L-arginine in cavernosal tissue from the Hch animals. Impairment of endothelium-dependent and neurogenic relaxation by CCI occurs secondary to disruption of the NO formation due to an alteration in the expression or activity of NOS and increased output of constrictor eicosanoids in cavernosal tissue. These studies show that Hch and atherosclerosis-induced chronic cavernosal arterial insufficiency, beyond decreasing cavernosal perfusion pressure, also adversely affect smooth muscle relaxation mechanisms in cavernosal tissue.

Sexual dysfunction associated with the management of prostate cancer.

Improvements in the management of prostate cancer have increased the need to consider patients' quality of life, in particular in relation to sexual function. The causes of sexual dysfunction are varied and derive from both the condition and its management. Health professionals must choose their treatment strategies with great care. Patient expectations must be understood, and patients should be offered counselling, as an understanding of what can reasonably be expected contributes to patients' perception of their quality of life. There are few studies on sexual dysfunction in patients with prostate cancer. A first step would be to develop reliable questionnaires for the assessment of the problem. This article describes and discusses the findings of one such recently developed questionnaire. When baseline measures of sexual function have been established and the extent of sexual dysfunction in patients with prostate cancer is reliably quantified, large multicentre trials can be performed to evaluate the impact of different therapies on sexual function and quality of life. Sexual dysfunction is an area which will be of increasing importance to urologists who manage prostate cancer and one that should not be underestimated.

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 in proposed.

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 Masson's 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.

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: (1) high intracavernosal pressure values (rigidity was related to pressure in an exponential-like fashion); (2) high penile aspect ratio (D/L) values (relatively large diameter/short length penile geometry) and high flaccid diameter; and (3) 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.

Percutaneous core biopsy of the penis.

To describe the efficacy of percutaneous core biopsy of penile corporal tissue, on ten impotent men, the biopsy was performed with a 19 and a 20 gauge core biopsy co-axial system using an automatic biopsy device. All biopsies were performed on an outpatient basis under local anesthesia. Adequate biopsy specimens were obtained in all. Percutaneous core biopsy of the penis is a safe procedure that is technically easy to perform.