Intracavernosal Blood Research Articles

Accurate and time-saving, two-step intracavernosal injection procedure to diagnose psychological erectile dysfunction.

BackgroundThe recognition of the erectile dysfunction pathogenesis is essential to identify the appropriate erectile dysfunction management. As vascular erectile dysfunction could be a manifestation of a systemic arterial damage, the watershed in the erectile dysfunction diagnostic framework is the discrimination between psychological erectile dysfunction and vascular erectile dysfunction. However, reliable tools to directly diagnose psychological erectile dysfunction are currently lacking.ObjectiveTo identify which parameters could predict psychological erectile dysfunction. Moreover, we suggest a new intracavernosal injection procedure to optimize the erectile dysfunction diagnostic workup.Materials and methodsA retrospective, real‐world analysis was carried out including all men who underwent intracavernosal injection procedure at the Modena Andrology Unit from 2018 to 2021. A first intracavernosal injection procedure with 5 µg of prostaglandin E‐1 (PGE‐1) was performed. In the absence of a full drug‐induced erection (immediate or delayed), an echo‐color Doppler penile evaluation after administration of PGE‐1 10 µg was conducted, measuring intracavernosal blood flows, to document a possible vascular etiology. Hormonal evaluations were performed.ResultsOut of 179 enrolled patients, 70.4% showed psychological erectile dysfunction, 21.7% vascular erectile dysfunction, and 7.8% hormonal genesis. Multinomial logistic regression analysis identified absence of cardiovascular disease (p = 0.017), presence of spontaneous morning erections (p = 0.018), and normal penile erections with masturbation (p = 0.035) as predictors of psychological erectile dysfunction. Clinically, normal intracavernosal injection test response was detected in 86 patients and abnormal response in 93 subjects. Among the latter, 54 patients experienced a delayed response. The combination of intracavernosal injection test with late penile erections evaluation was able to diagnose psychological erectile dysfunction (sensitivity 97%, specificity 100%), avoiding unnecessary retesting.DiscussionWe propose a two‐step intracavernosal injection procedure that allows to recognize psychological erectile dysfunction with a high sensitivity/specificity, saving costs and time, and limiting adverse events. Moreover, the presence of spontaneous morning erections and valid penile erections after masturbation could guide the diagnostic workup, indirectly identifying those patients deserving of a deeper evaluation of vascular health.

A rare but significant cause of priapism in the elderly: multiple myeloma

Priapism is a rare symptom with diverse etiological factors. Although most cases in adults are secondary to drug use and intracavernosal injections, blood dyscrasias and hypercoagulable states, vasculitis, penile metastases, neurological conditions, spider bites, carbon monoxide poisoning, and total parenteral nutrition may also result in priapism. We report a case of recurrent and refractory priapism in a 61-year-old man which was diagnosed as multiple myeloma after emergence of hypercalcemia and renal failure due to progression of the underlying pathology. The value of the initial diagnostic approach is emphasized.

Dietary antioxidants improve arteriogenic erectile dysfunction

Most cases of erectile dysfunction (ED) are associated with oxidative stress risk factors such as diabetes mellitus, smoking, hypercholesterolaemia and hypertension. Our goal was to search for markers of oxidative stress in arteriogenic ED and examine the protective role of dietary antioxidants. Atherosclerosis-induced ED was developed in rabbits by balloon de-endothelialization of the iliac arteries. Ballooned and age-matched control animals were assigned into subgroups receiving pomegranate extract antioxidants in drinking water or tap water as placebo. After 8 weeks, penile blood flow and erectile activity were recorded. Erectile tissue relaxation, oxidative products, oxidative stress-responsive genes and structure were examined using organ bath, enzyme immunoassay, quantitative real-time polymerase chain reaction and transmission electron microscopy, respectively. Arterial ballooning caused diffused atherosclerosis, decreased intracavernosal blood flow and led to ED. Impairment of endothelium-dependent relaxation, diffused fibrosis, increased oxidative products, upregulation of superoxide dismutase (SOD) and aldose reductase (AR) gene expression, mitochondrial and endothelial structural damage and increased caveolae were evident in erectile tissues from atherosclerotic animals receiving placebo. Upregulation of antioxidant enzymes SOD and AR failed to protect ischaemic erectile tissue from oxidative injury. Pomegranate extract significantly improved intracavernosal blood flow, erectile activity, smooth muscle relaxation and fibrosis of the atherosclerotic group in comparison with the atherosclerotic group receiving placebo, but did not normalize them to the age-matched control levels. Pomegranate extract appeared more effective in diminishing oxidative products, preventing SOD and AR gene upregulation, and protecting mitochondrial, endothelial and caveolae structural integrity of the atherosclerotic group. Our data suggest the presence of oxidative stress in ED and a more efficient action of antioxidants on molecular and ultrastructural alterations than on distinct functional deficit and structural damage in the ischaemic penis.

Oxidative stress and neurodegeneration in penile ischaemia

To seek markers of oxidative stress and examine neural structural integrity in chronic penile ischaemia using a rabbit model of arteriogenic erectile dysfunction (ED), as the role of ischaemia in penile neuropathy and the oxidative mechanism of neurodegeneration in ED remains unknown. A rabbit model of atherosclerosis-induced ED was developed by partial balloon de-endothelialization of the iliac arteries. After 10 weeks, intracavernosal blood flow and erectile function in the arteriogenic ED group were compared with age-matched controls. Erectile tissues were processed for analysis of oxidative stress markers and nerve fibre density using enzyme immunoassay and immunohistochemical staining, respectively. Oxidative stress-sensitive genes were determined with quantitative real-time polymerase chain reaction. Tissue ultrastructure was examined by transmission electron microscopy. Significant erectile tissue ischaemia, erectile dysfunction, increased levels of oxidative products, and marked nitrotyrosine immunoreactivity was evident in the ED group. Oxidative stress-sensitive genes encoding hypoxia inducible factor-1alpha (HIF-1alpha), superoxide dismutase (SOD), aldose reductase (AR) and nerve growth factor (NGF) were up-regulated in the ischaemic erectile tissue. These changes were associated with collapsed axonal and Schwann cell profiles, neurodegeneration, mitochondrial structural damage, increased caveolae, loss of endothelium, and sporadic vacuolization. Neuropathy appears to follow the vascular insult in arteriogenic ED. Neural injury in penile ischaemia involves a neurovascular phenomenon mediated by oxidative free radicals. Mitochondrial structural damage and increased HIF-1alpha gene expression may be early signals of oxidative stress and neurodegeneration in ED. Up-regulation of SOD, AR and NGF may be a coordinated defensive reaction to oxidative radicals that seems to fail to prevent neural injury in the ischaemic penis. Our study introduces the concept of oxidative neurodegeneration in the pathophysiology of arteriogenic ED. Therapeutic strategies to protect penile nerves from free radical incursion may enhance the efficacy of surgical and pharmacological interventions in arteriogenic ED.

Reversal of Voltage‐Dependent Erectile Responses in the Zucker Obese‐Diabetic Rat by Rosuvastatin‐Altered RhoA/Rho‐kinase Signaling

The combination of independent risk factors for erectile dysfunction, obesity, hypertension, and diabetes are collectively manifested in a condition known as metabolic syndrome X (MSX). However, the regulatory mechanisms responsible for the erectile dysfunction (ED) are not fully understood. Clinical studies suggest that a pleiotropic effect of statin's ability to enhance vascular relaxation might be through an impact on nitric oxide signaling or through a regulation of RhoA activation. We hypothesized that regulatory aspects of short-term statin therapy involve the alteration of the RhoA/Rho-kinase signaling cascade and will reverse the ED seen in a rat model of MSX. The magnitude and sensitivity of the voltage-dependent maintenance of intracavernosal blood pressure and mean arterial blood pressure. These responses were correlated with tissue protein and mRNA expression levels of RhoA and Rho kinases. Erectile function was evaluated by assessing voltage-dependent stimulation of the cavernosal nerve in 16-20 weeks old lean and obese-diabetic Zucker rats treated with 5 mg/kg/day of rosuvastatin intraperitoneally for 3 days. Cavernosal tissue RhoA and Rho-kinases expression levels were evaluated by real-time reverse transcriptase-polymerase chain reaction, Western blot. The voltage-dependent erectile responses were suppressed by >30% in the obese-diabetic Zucker rat. The 3-day treatment with rosuvastatin partially restored the erectile response. The Rho-kinase inhibitor, H-1152, dose dependently increased the erectile responses and shifted the voltage sensitivity with statin treatment. Analysis of protein expression levels suggested elevation of RhoA and Rho kinases in obese-diabetics and statin treatment lowering Rho-kinase II. The RhoA and Rho-kinase II mRNA levels were significantly reduced in the rosuvastatin-treated obese-diabetic animals. These results support a hypothesis that short-term statin therapy may lower RhoA/Rho-kinase expression levels and improve cavernosal blood pressure response to Rho-kinase inhibition and voltage-stimulation, and reversing an augmented vasoconstricted state associated with diabetes and/or hypertension in MSX.

1052: Antioxidant Intake Increases Intraca Vernosal Blood Flow and Prevents Erectile Tissue Fibrosis

You have accessJournal of UrologyDiscussed Poster, Tuesday, May 24,2005, 8:00 am - 12:00 pm1 Apr 20051052: Antioxidant Intake Increases Intraca Vernosal Blood Flow and Prevents Erectile Tissue Fibrosis Kazem M. Azadzoi, Risa Schulman, Michael Aviram, and Mike B. Siroky Kazem M. AzadzoiKazem M. Azadzoi More articles by this author , Risa SchulmanRisa Schulman More articles by this author , Michael AviramMichael Aviram More articles by this author , and Mike B. SirokyMike B. Siroky More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)35208-XAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1052: Antioxidant Intake Increases Intraca Vernosal Blood Flow and Prevents Erectile Tissue Fibrosis." The Journal of Urology, 173(4S), p. 285 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 285 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Kazem M. Azadzoi More articles by this author Risa Schulman More articles by this author Michael Aviram More articles by this author Mike B. Siroky More articles by this author Expand All Advertisement PDF DownloadLoading ...

Adipocyte Accumulation in Penile Corpus Cavernosum of the Orchiectomized Rabbit: A Potential Mechanism for Veno‐occlusive Dysfunction in Androgen Deficiency

Androgens are deemed to be critical for the development, growth, and maintenance of penile tissue as well as for erectile function. Androgens are also reported to inhibit differentiation of stroma progenitor cells into adipocytes and promote differentiation into smooth muscle. The objective of this study was to investigate whether androgen deprivation results in accumulation of adipocytes in the corpus cavernosum. Mature, New Zealand white male rabbits were subjected to sham surgery (control) or orchiectomy. Two weeks after surgery, erectile function was assessed by monitoring changes in intracavernosal blood pressure (ICP) in response to pelvic nerve stimulation. All ICP measurements were normalized to the mean systemic arterial blood pressure. In parallel studies, penile cross sections from control and orchiectomized rabbits were fixed and stained with either Masson's trichrome or hematoxylin and eosin to assess smooth muscle and connective tissue content. Alternatively, tissue sections were stained with Toluidine blue to assess accumulation of fat-containing cells. Orchiectomy resulted in loss of erectile function and penile atrophy, associated with reduced trabecular smooth muscle and increased connective tissue content. Most strikingly, tissue from orchiectomized animals exhibited accumulation of fat-containing cells (adipocytes) in the subtunical region of the corpus cavernosum. We hypothesize that androgen deprivation promotes differentiation of progenitor stroma cells into an adipogenic lineage producing fat-containing cells, thus altering erectile function.

Effect of Chronic Ischemia on Constitutive and Inducible Nitric Oxide Synthase Expression in Erectile Tissue

Arterial occlusive disease is one of the leading causes of organic erectile dysfunction (ED). Recent studies have shown that the incidence of cardiovascular disease closely correlates with the prevalence of ED. Also, ED is thought to be an early signal of impending cardiovascular problems. We previously found that the atherosclerosis of iliohypogastric arteries in the rabbit causes ED, down-regulates cavernosal neuronal nitric oxide synthase (nNOS) gene expression, and impairs NO synthesis. The goal of this study was to determine the effect of atherosclerosis-induced ischemia on cavernosal nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) expression and NO-mediated smooth muscle relaxation in the rabbit. Our study showed that iliac artery blood flow, intracavernosal blood flow, and intracavernosal oxygen tension were unchanged 4 weeks after the induction of arterial atherosclerosis, whereas they were significantly diminished at weeks 8 and 16. Erectile responses to nerve stimulation and cavernosal smooth muscle relaxation were unchanged at week 4 and were significantly diminished at weeks 8 and 16 after the induction of atherosclerosis. Western blotting showed that cavernosal nNOS and eNOS protein levels were unaffected at week 4 but were significantly decreased at weeks 8 and 16 after the induction of atherosclerosis. iNOS protein, however, markedly increased during the course of the induced arterial disease. Immunohistochemical staining showed no change in cavernosal eNOS or nNOS expression at week 4. A dramatic decrease in both was evident at 8 and 16 weeks. iNOS expression progressively increased between 4 and 16 weeks of atherosclerosis. Down-regulation of nNOS and eNOS, along with up-regulation of iNOS, may explain ischemic cavernosal smooth muscle relaxation impairment in the rabbit. Ischemically altered NOS expression may be of great pathophysiologic importance in atherosclerosis-induced ED. These data may provide further insight into the mechanism of arteriogenic ED.

Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit.

Aging and menopause related decline in circulating levels of estrogen has been shown to adversely affect female sexual arousal function. Our aim was to study the effects of circulating levels of estrogen on the hemodynamic mechanism of vaginal and clitoral engorgement and on the structure of the vaginal and clitoral cavernosal tissue in the rabbit. New Zealand White female rabbits (3.5-4 kg) were randomly divided into three groups with five rabbits in each group: control; bilateral oophorectomy; bilateral oophorectomy undergoing subcutaneous injection of estrogen (40 microg/kg/day). After 6 weeks, the serum levels of 17 beta-estradiol were measured and systemic blood pressure was monitored. Vaginal and clitoral cavernosal blood flows were measured with laser Doppler flowmeter before and after pelvic nerve stimulation. Cross sections of the clitoris and vagina were processed for histologic examination and histomorphometric image analysis. Serum level of 17 beta-estradiol (pg/ml; mean+/-s.d.) revealed a significant decrease in the oophorectomy group (25.4+/-5.1) compared with the control (38.5+/-7.6) and estrogen replacement (115.9+/-57.3) groups (P<0.05). Nerve stimulation-induced peak vaginal and clitoral intracavernosal blood flows in the oophorectomy group (28.9+/-16.3 and 6.1+/-1.4, respectively) were significantly less than those recorded in the control (48.9+/-6.5 and 11.0+/-2.4, respectively) or estrogen replacement (48.7+/-12.2 and 10.1+/-2.8, respectively) group (P<0.05). In histology, marked thinning of the vaginal epithelial layers, decreased vaginal submucosal microvasculature, and diffuse clitoral cavernosal fibrosis were evident in the oophorectomy group but not in the estrogen supplement and control groups. In histomorphometry, the percentage of clitoral cavernosal smooth muscle in the oophorectomy group (49.6+/-6.2) was significantly decreased compared with the control (56.8+/-2.6) and estrogen replacement (58+/-3.0) groups (P<0.05). Our studies show that decline in circulating levels of estrogen impairs the hemodynamic mechanism of vaginal and clitoral engorgement and leads to histopathologic changes in the vagina and clitoral cavernosal tissue. These observations suggest that decreased circulating levels of estrogen, a physiologic change in the menopausal state, may play a role in the development of female sexual arousal dysfunction.

The loss of alpha-adrenergic effect during the erectile response in the long-term diabetic rat.

The present study was designed to investigate the effect of long-term, streptozotocin-induced diabetes on the erectile response in the laboratory rat. Mean arterial blood pressure (MAP) and intracavernosal blood pressure within the erectile tissue (CCP) were continuously monitored during erection elicited by stimulation of the autonomic innervation of the penis. MAP and CCP were also measured during administration of two drugs: nitroglycerin, a nitric oxide donor drug and phenylephrine, an alpha-adrenergic agonist. The results of these studies show that during graded electrical stimulation of the ganglion, the overall magnitude of the erectile response was greater in the diabetic rats than in untreated control animals. Neither diabetic nor control animals responded significantly to infusion of nitroglycerin. However, diabetic rats and control rats responded very differently to administration of phenylephrine; in the control rats, this alpha agonist caused a sharp decline in CCP as the cavernosal vessels constricted in response to the drug. The same dose of phenylephrine had no discernible effect on CCP in the diabetic animals. This loss of alpha responsiveness may be confined to the penile circulation because MAP was elevated to approximately the same extent in both groups. Taken together, these results show that long-term diabetes leads to a failure of alpha-adrenergic responsiveness in the cavernosal circulation. The greater erectile response to ganglionic stimulation in the diabetic animals is likely due to the loss of response to endogenous norepinephrine.

Relationship Between Cavernosal Ischemia and Corporal Veno-Occlusive Dysfunction in an Animal Model

It has been postulated that cavernosal tissue ischemia secondary to arterial occlusive disease is associated with corporal veno-occlusive dysfunction. The goal was to correlate, for the first time, direct local intracavernosal blood flow measurements as a measure of cavernosal tissue perfusion with the integrity of corporal veno-occlusion in an animal model of vasculogenic impotence. The New Zealand White rabbit model of vasculogenic impotence was utilized (7 control, 9 atherosclerotic). After 16 weeks, intracavernosal blood flow was recorded directly by laser Doppler flowmetry. The relationships among peak intracavernosal blood flow, equilibrium intracavernosal pressure and corporal veno-occlusive function (as determined by intracavernosal pressure decay) were examined. Significant differences in the atherosclerotic compared to control animals were noted in iliac artery blood flow (12 +/- 4 vs 31 +/- 7 ml./min.), peak intracavernosal blood flow during erection (16 +/- 7 vs 25 +/- 4 ml./min./100 gm. tissue), equilibrium intracavernosal pressure (48 +/- 11 vs 72 +/- 6 mm. Hg) and intracavernosal pressure decay (57 +/- 17 vs 36 +/- 8 mm. Hg). Peak intracavernosal blood flow during erection was found significantly related to both equilibrium pressure (r = 0.75) and cavernosal pressure decay (r = -0.8). Abnormal intracavernosal blood flow (cavernosal ischemia) secondary to arterial occlusive disease predicts abnormal veno-occlusive function and poor erection quality.

Hemodynamics of Penile Erection: III. Measurement of Deep Intracavernosal and Subtunical Blood Flow and Oxygen Tension

Previous studies have shown that intracavernosal blood flow increases during penile erection, but little is known about intracavernosal hemodynamics. Using a previously developed canine model of erection, we measured intracavernosal blood flow and oxygen tension at 2 sites within the corpus cavernosum: directly beneath the tunica albuginea and deep within the cavernous tissue. We chose to measure oxygen tension as an indicator of arterial blood flow. Penile erection was induced by pelvic nerve stimulation as well as by injection of papaverine and phentolamine. In the flaccid penis, blood flow measured directly under the tunica albuginea was significantly higher than deep intracavernosal blood flow. Subtunical oxygen tension in the flaccid penis was consistent with a largely arterial circulation. These observations provide physiological evidence of an important subtunical circulation that carries most of the intracavernosal blood flow when the penis is flaccid. With pelvic nerve stimulation, deep intracavernosal blood flow increased significantly followed by an increase in oxygen tension. Oxygen tension deep within the corpus cavernosum increased during penile erection from a level consistent with venous blood to a level consistent with arterial blood. Injection of papaverine and phentolamine caused a significant increase in intracavernosal pressure and a significant decrease in subtunical blood flow but did not cause statistically significant change in intracavernosal blood flow or oxygen tension. In contrast to nerve-induced erection, pharmacologically induced erection appears to depend more on intracavernosal shunting of blood than on increased total arterial blood flow to the penis. Hypogastric nerve stimulation during established erection caused detumescence by contracting cavernosal smooth muscle, reducing deep cavernosal blood flow and reestablishing blood flow through the subtunical space. Our observations suggest that the subtunical space contains an important circulation that may play a role in the hemodynamics of the flaccid, as well as the erect, penis.