Vesico-obturator venous plexus - a rare termination of obturator vein.

Obturator vein usually terminates into the internal iliac vein. Its variations are the cause major bleeding problems in pelvic surgeries. We observed a rare variation in the termination of the right obturator vein. There was a duplication of right obturator vein. Both obturator veins entered the pelvic cavity through the obturator foramen and joined with two vesical veins to form a vesico-obturator plexus. This plexus surrounded the internal iliac artery and terminated into the internal iliac vein. Awareness of this rare variation could be of importance to anatomists, radiologists, gynaecologists, urologists, and orthopaedic surgeons. The plexus might lead to hazardous bleeding in pelvic lymph node clearance procedures, hernia surgeries, gynaecological and orthopaedic procedures in this region. The pelvic fractures too can provoke dramatic retroperitoneal hematomas related to these veins injuries.

Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2-Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat.

We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured the expression of mast cell tryptase (MCT) and protease-activated receptor 2 (PAR2), which are correlated with C fiber activation via MCT, and Uroplakins (UP Ia, Ib, II and III), which are critical to urothelial barrier function, via Western blotting. The effects of FSLLRY-NH2, a PAR2 antagonist, administered intravenously, on the bladder function of CBI rats were evaluated with a cystometrogram. In the CBI group, the MC number in the bladder was significantly greater (p = 0.03), and the expression of MCT (p = 0.02) and PAR2 (p = 0.02) was significantly increased compared to that of the control group. The 10 µg/kg FSLLRY-NH2 injection significantly increased the micturition interval of CBI rats (p = 0.03). The percentage of UP-II-positive cells on the urothelium with immunohistochemical staining was significantly lower in the CBI group than in the control group (p < 0.01). Chronic ischemia induces urothelial barrier dysfunction via impairing UP II, consequently inducing MC infiltration into the bladder wall and increased PAR2 expression. PAR2 activation by MCT may contribute to bladder hyperactivity.

Posttraumatic hemorrhagic bladder rupture managed with transurethral foley catheter placement and bilateral transcatheter vesical artery embolization.

BACKGROUND: Outcome of minimally invasive treatment of posttraumatic, hemorrhagic bladder rupture is unknown. METHODS: A 41-year-old male presented at the emergency department with pelvic and scrotal pain and macroscopic hematuria after a motor vehicle accident. Contrast-enhanced computed tomography revealed an open book fracture and an arterial phase contrast media extravasation posterior to the symphysis pubis and anterior to the urethra-vesical junction. RESULTS: The open book fracture was treated with an external fixation and the persistent bleeding was managed with insertion of a Foley catheter and bilateral embolization of the vesical arteries. CONCLUSION: Minimally invasive treatment, including vesical artery embolization and placement of a Foley catheter can be effective in the treatment of posttraumatic, hemorrhagic bladder rupture.

Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver Model.

PURPOSE: The purpose of this study was to establish the feasibility of performing a urinary bladder vascularized composite allograft transplantation for either bladder augmentation or neobladder creation. MATERIALS AND METHODS: Six adult cadavers were studied. Cadavers were excluded for any previous pelvic surgery, radiation, vascular surgery or history of pelvic malignancy. An intravascular colored silicone and barium mixture was injected and both computerized tomography scans and gross dissections were performed. Contrast enhanced computerized tomography imaging was used to delineate urinary bladder vascular anatomy variability. Bladders were explanted en bloc from 2 cadavers with bilateral vascular pedicles based on the external iliac vessels and "transplanted" to replicate a bladder transplant. RESULTS: Contrast enhanced 3-D-computerized tomography reconstructions and cadaver dissections revealed distal vascular variability with proximal blood supply based primarily on the internal iliac artery. Urinary bladder vascularized composite allograft transplantation was successfully performed during 2 mock transplants with the vascular anastomosis done to the recipient external iliac artery and vein. CONCLUSIONS: Urinary bladder vascularized composite allograft transplantation is technically and anatomically feasible. This procedure may obviate the use of intestinal segments for bladder reconstruction in select patients. A phase 1 clinical trial is in progress.

Fetal Urinoma Due to Circulatory Disorders in an Umbilical Artery: Case Report.

Fetal urinoma is defined as an encapsulated accumulation of extravasated urine within the perirenal space or retroperitoneum. It is an uncommon finding in prenatal practice, and the vast majority of known cases are strongly associated with the existence of a urinary obstruction, such as posterior urethral valves, ureteropelvic junction obstruction, or ureterocele. We report a unique case of prenatally detected fetal bladder urinoma that occurred in the absence of an apparent obstructive uropathy, but was associated with extensive ischemic necrosis and calcifications of adjacent bladder wall, coexistent with signs of vascular supply decompensation.

Superselective vesical artery embolization for intractable bladder hemorrhage related to pelvic malignancy.

BACKGROUND: Intractable bladder hemorrhage from pelvic malignancy can be potentially life-threatening and its management can be a challenging clinical problem. PURPOSE: To evaluate safety, efficacy, and clinical outcome of superselective vesical artery embolization for the control of intractable bladder hemorrhage from pelvic malignancy. MATERIAL AND METHODS: Between January 2010 and September 2018, 20 patients underwent superselective vesical artery embolization for intractable hematuria secondary to pelvic malignancy arising from or invading the bladder. Treatment details and clinical outcomes were obtained. RESULTS: There were 12 men and 8 women (mean age = 77 years). Bilateral embolization was performed in 10 patients and unilateral approach in 10 patients. Two patients died within four days after embolization due to underlying heart failure and systemic metastasis, respectively. The remaining 18 patients had a follow-up of >30 days. Bleeding was controlled after the first embolization in 17/18 patients and after a repeat embolization in the remaining one patient. The mean follow-up period of 18 patients was 10.6 months (range = 1-77 months). Late recurrent hemorrhage (≥ 30 days after embolization) was reported in 6 (33.3%) patients. Five of these six patients underwent repeat embolization. There were no major complications related to embolization. CONCLUSION: Palliative superselective vesical artery embolization is a feasible, effective, and safe procedure to control intractable hematuria in patients with pelvic malignancy.

Hypothermia induces opposite response in vascular and non-vascular smooth muscles.

BACKGROUND AND AIM: The mechanism of cooling-induced response of smooth muscles remains little understood despite the increasing importance given to it in recent years. The aim of this study was to examine the possibility of releasing a relaxant or a contractile substance during cooling from vascular and non-vascular smooth muscles. METHODS: Assessing the effect of cooling for two different smooth muscles together, vascular (aorta or carotid) which induced relaxation, and non-vascular (jejunum or bladder) which induced contraction. Hanging a pair of smooth muscle strips from different body organs in the same organ bath filled with Krebs solution, each strip was connected to its own transducer and recorder and stepwise cooling was applied. Recordings of isometric tension using organ-bath techniques. RESULTS: Step-wise cooling (37 °C-4 °C) of aorta and carotid smooth muscle preparations induced reproducible graded relaxation while jejunum and bladder preparations induced reproducible graded tonic contractions, inversely proportional to temperature. The responses of all the smooth muscle preparations were the same magnitude either alone or as a pair in the organ bath. Cooling abolished rhythmic smooth muscle activity of jejunum and bladder. Cooling-induced contraction was reduced by incubation in Ca2+-free solution. The effect of cooling either relaxation or contraction was not enhanced or attenuated by the presence of the two different smooth muscles with opposite response in the same organ bath, proving the absence of a relaxant or a contractile substance released during cooling. CONCLUSIONS: Cooling of aorta and carotid artery induced relaxation while jejunum and bladder induced contraction. The response to cooling is inversely proportional to the temperature. There was neither a relaxant nor a contractile substance released from vascular or non-vascular smooth muscles during cooling. Our study suggested that the effect of cooling is through a thermal receptor with two subtype one in the vascular smooth muscle (deep blood vessels) which induces relaxation, and the second in non-vascular smooth muscles (non-vascular organs) that induces contraction and the responses depend on extracellular calcium.

The effect of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction.

PURPOSE: To evaluate the effects of mirabegron on bladder blood flow in a rat model of bladder outlet obstruction (BOO). METHODS: Adult female Sprague-Dawley rats were divided into three groups based on whether they underwent a sham operation (sham group) or an operation to establish partial BOO (BOO and BOO + mirabegron groups). The BOO + mirabegron group was treated with mirabegron (0.3 mg/kg/h, subcutaneously) for 14 days. Subsequently, we performed continuous cystometry, bladder blood flow measurements with a 2D laser blood flow imager, hematoxylin-eosin staining of the bladder tissue, and malondialdehyde (MDA) measurements in the bladder tissue. RESULTS: Cystometry revealed significantly higher peak pressure, more residual urine volume, and lower voiding efficiency in the BOO and BOO + mirabegron groups than in the sham group. The BOO + mirabegron group had significantly fewer non-voiding contractions (NVCs) than the BOO group, while the latter had more frequent NVCs than the sham group. The BOO and BOO + mirabegron groups had significantly decreased bladder blood flow than the sham group, whereas the BOO + mirabegron group showed significantly increased bladder blood flow than the BOO group. The bladder tissue in the BOO group contained more hypertrophic detrusor muscle compared to the sham group, while mirabegron treatment suppressed detrusor hypertrophy. The MDA levels were significantly higher in the BOO group than in the BOO + mirabegron and sham groups. CONCLUSION: Mirabegron treatment significantly improved BOO-induced bladder dysfunction through the amelioration of bladder blood flow.

Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019.

Several studies indicate that pelvic ischemia and oxidative stress may play a significant role in lower urinary tract dysfunction (LUTD), including detrusor overactivity (DO)/overactive bladder (OAB) and detrusor underactivity (DU)/underactive bladder (UAB). The present article addresses proposal 1: "Are oxidative stress and ischemia significant causes of bladder damage leading to LUTD?" from the 2019 International Consultation on Incontinence-Research Society (ICI-RS) meeting. Bladder ischemia in animals and humans is briefly described, along with the proposed progression from ischemia to LUTD. Bladder ischemia is compared with ischemia of other organs, and the ongoing development of pelvic ischemia animal models is discussed. In addition, the distribution of blood within the bladder during filling and voiding and the challenges of quantification of blood flow in vivo are described. Furthermore, oxidative stress, including potential biomarkers and treatments, and challenges regarding antioxidant therapy for the treatment of LUTD are discussed. Finally, seven critical research questions and proposed studies to answer those questions were identified as priorities that would lead to major advances in the understanding and treatment of lower urinary tract symptoms (LUTS)/LUTD associated with pelvic ischemia and oxidative stress.

Excitability and contractility in arterioles and venules from the urinary bladder.

The urinary bladder performs two key physiological functions: (1) to store urine, and (2) void urine at an appropriate time. While these two functions seem simple, both processes exert prolonged stretch and compressive forces on the urinary bladder vasculature that are greater than those seen by vessels in any other hollow organ. To compensate for these forces, the urinary bladder vasculature has adapted several key features that maintain blood flow during bladder filling and prevent damaging pressure fluctuations during emptying. This chapter first describes key anatomical features of the urinary bladder vasculature and how these features aid in maintaining blood flow in the milieu of the functioning bladder. Next, we investigate the mechanisms regulating excitability of urinary bladder arterioles with emphasis on the development and regulation of myogenic tone. We then discuss the physiological significance and excitability of urinary bladder capillaries and venules, and their important roles in maintaining tissue perfusion. Finally, the functionality of the urinary bladder vasculature will be explored in terms of bladder dysfunction, to understand if lower urinary tract symptoms associated with disease can be considered vascular in nature. Also included are perspectives on the urinary bladder itself as a model for understanding ischemia/reperfusion injury and the possibility that the urinary bladder holds a key to mitigating deleterious effects that result when blood flow is occluded and rapidly restored to other organs.

Three-Dimensional Peripheral Bloodstream Model of the Uterus for Laparoscopic Radical Hysterectomy.

Trainees require extensive experience to perform radical hysterectomy. Before starting training during an actual operation, trainees should be familiar with the pelvic anatomy and should simulate surgical procedures. Many simulators are available for virtual reality training of laparoscopic operations, but they are very expensive. The materials required to construct our model included sponges and colored wires sold in home improvement stores that allowed for superior cost effectiveness. The model represented almost all peripheral vessels and nerves around the uterus, including the minor vessels. Attaching and detaching the vessels was easy, facilitating reconstruction of the dissected vessels. The wires were easy to bend, ensuring high operability. This model allows for the simulation of laparoscopic radical hysterectomy in a dry box. Our model was superior to a 2-dimensional picture for the memorization of branching and positional relationships of the blood vessels. Comparison of our model with actual operative videos showed that the dry box provided an identical surgical view of an actual laparoscopic radical hysterectomy. We developed a peripheral bloodstream model of the uterus for repeated simulation of laparoscopic radical hysterectomy with an actual surgical view using a dry box.

Molecular Taxonomy of Interstitial Cystitis/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies.

PURPOSE: We systematically characterized gene expression, inflammation and neovascularization in patients with interstitial cystitis/bladder pain syndrome to obtain biological evidence supporting diagnosis and classification. MATERIALS AND METHODS: We sequenced RNA obtained from bladder mucosal biopsies of 33 patients with 3 subtypes of interstitial cystitis/bladder pain syndrome, including Hunner lesions in 12, no Hunner lesions in 11 but with glomerulations and neither Hunner lesions nor glomerulations in 10, and 9 controls. Differentially expressed genes of each subtype were searched to identify subtype specific biological pathways and candidate genes important for pathogenesis. Candidate genes were validated by quantitative polymerase chain reaction and immunohistochemistry. Digital immunohistochemical quantification was performed to assess subepithelial lymphoplasmacytic cell and microvessel density. Relationships between candidate gene over expression and symptom severity were explored. RESULTS: Patients with Hunner lesions showed a distinct gene expression profile associated with significant up-regulation of biological processes involving immune responses and infection, and an increase in subepithelial lymphoplasmacytic cell and microvessel density. Over expression of 2 candidate genes, VEGF and BAFF, correlated with symptom severity. Meanwhile, the gene expression profiles of patients with the 2 subtypes without Hunner lesions were similar to those of controls. No difference in biological pathways or subepithelial lymphoplasmacytic cell and microvessel density were detected between these 2 subtypes and controls. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome with Hunner lesions shows distinct genomic and histological features associated with immune responses and infection. In addition, VEGF and BAFF are potential disease biomarkers and therapeutic targets. This subtype should be considered separate from the syndrome.

Superselective vesical artery embolization in the management of intractable hematuria secondary to hemorrhagic cystitis.

PURPOSE: To evaluate the efficacy and outcome of superselective vesical arterial embolization in the management of severe intractable hematuria secondary to hemorrhagic cystitis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of nine patients with severe intractable hematuria treated with superselective vesical artery embolization at our institution between March 2003 and February 2015. There were six males and three females with a mean age of 56.1 years. Seven patients had transitional cell carcinoma (TCC) of urinary bladder and had undergone transurethral resection of bladder tumor and pelvic radiotherapy. One patient had synchronous renal pelvis and bladder TCC. One patient had aortoarteritis and was receiving cyclophosphamide therapy and another patient had carcinoma cervix post-pelvic radiotherapy. Following the failure of conservative management, superselective vesical artery catheterization and embolization was performed with 300-500-µ PVA particles in all patients. Coil embolization of inferior gluteal artery followed by particle embolization of vesical arteries was done in one patient in whom superior, inferior vesical and inferior gluteal arteries were arising as a trifurcation. RESULTS: The technical success rate was 100% with complete cessation of hematuria within 48 h in all patients. No significant complications were noted, except for post-embolization syndrome in one patient, which improved on symptomatic treatment. During a mean follow-up period of 14.45 months (ranging from 3-28 months), one patient had mild recurrent hematuria (at 2 months) which resolved spontaneously. CONCLUSIONS: Superselective vesical artery embolization is a safe and effective procedure in controlling intractable life-threatening hematuria in a select group of patients who have failed conventional treatment protocols. This procedure may be considered as the treatment of choice since it usually obviates the need for emergency surgery in these severely ill patients.

Is bladder blood flow an etiologic factor for the bladder pain syndrome?

AIM: Bladder pain syndrome (BPS) is a complex disease which causes cognitive, behavioral, sexual, and emotional problems. Vascular factors related to bladder blood supply may be one of the etiologic cause of BPS. This study aims to investigate the bladder blood flow and internal iliac artery resistive indices of patients with BPS. METHODS: A total of 30 female patients with the diagnosis of BPS and 30 female as control group were enrolled in the study. Bilateral internal iliac arterial blood flow distal to uterine arteries were examined as the primary source of vesical arterial blood supply. Peak systolic velocities, end diastolic velocities, resistive indices, and flow volumes of internal iliac arteries were measured by color Doppler ultrasonography in a single-blind fashion. RESULTS: The blood flows volume of the right and left internal iliac arteries during empty and full bladder were significantly lower at BPS group compared with control (P < 0.05). Although the difference was not significant, the mean resistive index of right and left internal iliac arteries were lower at the control group ( P > 0.05). Aging decreased the bladder blood volume and both BPS and control group internal iliac artery blood volume decreased by aging. The decrease was more significant at the control group, but the internal iliac artery blood volume was still lower at patients with BPS compared with the control group. CONCLUSION: Arterial blood flow of bladder was lower at patients with BPS compared with the control group. The decrease in the vascular supply of bladder might be one of the related factors for the BPS etiology.

Spinal glycinergic and gamma-aminobutyric acid-ergic neurons inhibit the micturition reflex after electrical stimulation of the perineum in rats with pelvic venous congestion.

OBJECTIVES: To examine whether electrical stimulation of the perineum inhibited urinary frequency in rats with pelvic venous congestion, and whether electrical stimulation influences spinal glycinergic/gamma-aminobutyric acid-ergic neurons. METHODS: Bilateral common iliac veins and bilateral uterine veins were ligated to create pelvic venous congestion rats. At 4 weeks after ligation, cystometry was carried out before and after electrical stimulation with/without intrathecal injection of strychnine (a glycine receptor antagonist) and/or bicuculline (a gamma-aminobutyric acid type A receptor antagonist). In addition, measurement of amino acid levels in the lumbosacral cord was carried out with/without electrical stimulation, and cystometry was carried out after oral administration of glycine. RESULTS: Continuous cystometry showed that the interval between bladder contractions was shorter in pelvic venous congestion rats than in sham rats. Electrical stimulation did not change cystometric parameters in sham rats, but the interval between bladder contractions was increased by electrical stimulation in pelvic venous congestion rats. Electrical stimulation increased the levels of glutamic acid, glycine, gamma-aminobutyric acid, and taurine in the lumbosacral cord of pelvic venous congestion rats. Intrathecal strychnine abolished the effects of electrical stimulation in pelvic venous congestion rats, and intrathecal administration of both strychnine and bicuculline shortened the interval between bladder contractions more than before electrical stimulation. Oral administration of glycine (3%) to pelvic venous congestion rats increased bladder capacity. CONCLUSIONS: Electrical stimulation of the perineum inhibits urinary frequency mainly through activation of spinal glycinergic neurons, and partly through activation of gamma-aminobutyric acid-ergic neurons in a rat model of pelvic venous congestion.

Effectiveness of the combination of vascular targeted photodynamic therapy and anti-cytotoxic T-lymphocyte-associated antigen 4 in a preclinical mouse model of urothelial carcinoma.

OBJECTIVE: To investigate the effectiveness of combination treatment of vascular targeted photodynamic therapy and anti-cytotoxic T-lymphocyte-associated antigen 4 immunotherapy in a mouse model of urothelial carcinoma. METHODS: We used C57BL/6 mice injected with murine bladder 49 cell line. Mice were randomly allocated into four treatment groups: vascular targeted photodynamic therapy only, anti-cytotoxic T-lymphocyte-associated antigen 4 only, combination therapy and control. We carried out three separate experiments that used distinct cohorts of mice: tumor growth and development of lung metastases monitored with bioluminescent imaging (n = 91); survival evaluated with Kaplan-Meier curves (n = 111); and tumor cell population studied with flow cytometry (n = 20). In a fourth experiment, we re-challenged tumors in previously treated mice and compared tumor growth with that of naïve mice. RESULTS: Combination therapy provided significant benefits over the other three treatment groups: prolonged survival (P < 0.0001), lower tumor signal (P < 0.0001) and decreased lung signal uptake (P ≤ 0.002). We also observed that mice previously treated with vascular targeted photodynamic therapy only or combination therapy did not present tumor growth after re-challenged tumors. CONCLUSIONS: Combination of vascular targeted photodynamic therapy with anti-cytotoxic T-lymphocyte-associated antigen 4 is an effective therapy in a urothelial carcinoma syngeneic mouse model. The present results suggest this therapy as a potential treatment option for both bladder and upper tract tumors in future clinical trials.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Diagnostic Tool in the Assessment of Tumour Angiogenesis in Urinary Bladder Cancer.

PURPOSE: The aim of study is to assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and correlation with tumour angiogenesis in evaluation of urinary bladder cancer. MATERIAL AND METHODS: The study included 81 patients with recent presumed diagnosis of bladder tumour or who came for follow up after management of histopathologically proven bladder cancer. All had DCE-MRI with time-signal intensity curve. The radiologic results then correlated with the histopathologic results using both haematoxylin and eosin stain and immuno-histochemical staining for localization and evaluation of CD34 immunoreactivity as a detector for the microvessel density (MVD) and tumour angiogenesis. RESULTS: Seventy-one cases were pathologically proven to be malignant: 41 cases (58%) showed type III time-signal intensity curve (descending); 22 cases (31%) showed type II (plateau); and 8 cases (11%) showed type I (ascending) curve. The sensitivity of DCE-MRI in stage T1 bladder tumour was 80%; in stage T2, it was (90.9%); and in stage T3, it was (96.9%). Overall accuracy of DCE-MRI in tumour staging was 89.5% and P = .001 (significant). Values more than the cutoff value = 76.13 MVD are cystitis with sensitivity (90%), specificity (91%), and P value is .001, which is statistically highly significant. CONCLUSION: There is a strong positive association between DCE-MRI (staging and washout slope of the time-signal intensity curve) with histopathologic grade, tumour stage, and MVD in bladder cancer. So, DCE-MRI can be used as reliable technique in preoperative predictions of tumour behavior and affect the planning of antiangiogenetic therapy.

[Detrusor ischemia. linical effects].

Three basic theories of the development of an overactive bladder that have experimental and clinical evidences have been described, including neurogenic, myogenic, and urothelial. Based on the results of the literature analysis, the authors suggested the existence of detrusor ischemic disease as a result of compressive impairment of its blood flow due to incomplete or short-term relaxation under overactivity or hydraulic compression of the vessels by excessive urine volume in case of hypoactive bladder.

Role of capillary pericytes in the integration of spontaneous Ca2+ transients in the suburothelial microvasculature in situ of the mouse bladder.

KEY POINTS: In the bladder suburothelial microvasculature, pericytes in different microvascular segments develop spontaneous Ca2+ transients with or without associated constrictions. Spontaneous Ca2+ transients in pericytes of all microvascular segments primarily rely on the cycles of Ca2+ uptake and release by the sarco- and endoplasmic reticulum. The synchrony of spontaneous Ca2+ transients in capillary pericytes exclusively relies on the spread of depolarizations resulting from the opening of Ca2+ -activated chloride channels (CaCCs) via gap junctions. CaCC-dependent depolarizations further activate L-type voltage-dependent Ca2+ channels as required for the synchrony of Ca2+ transients in pericytes of pre-capillary arterioles, post-capillary venules and venules. Capillary pericytes may drive spontaneous Ca2+ transients in pericytes within the suburothelial microvascular network by sending CaCC-dependent depolarizations via gap junctions. ABSTRACT: Mural cells in the microvasculature of visceral organs develop spontaneous Ca2+ transients. However, the mechanisms underlying the integration of these Ca2+ transients within a microvascular unit remain to be clarified. In the present study, the origin of spontaneous Ca2+ transients and their propagation in the bladder suburothelial microvasculature were explored. Cal-520 fluorescence Ca2+ imaging and immunohistochemistry were carried out on mural cells using mice expressing red fluorescent protein (DsRed) under control of the NG2 promotor. NG2(+) pericytes in both pre-capillary arterioles (PCAs) and capillaries developed synchronous spontaneous Ca2+ transients. By contrast, although NG2-DsRed also labelled arteriolar smooth muscle cells, these cells remained quiescent. Both NG2(+) pericytes in post-capillary venules (PCVs) and NG2(-) venular pericytes exhibited propagated Ca2+ transients. L-type voltage-dependent Ca2+ channel (LVDCC) blockade with nifedipine prevented Ca2+ transients or disrupted their synchrony in PCA, PCV and venular pericytes without dis-synchronizing Ca2+ transients in capillary pericytes. Blockade of gap junctions with carbenoxolone or Ca2+ -activated chloride channels (CaCCs) with 4,4'-diisothiocyanato-2,2'-stilbenedisulphonic acid disodium salt prevented Ca2+ transients in PCA and venular pericytes and disrupted the synchrony of Ca2+ transients in capillary and PCV pericytes. Spontaneous Ca2+ transients in pericytes of all microvascular segments were abolished or suppressed by cyclopiazonic acid, caffeine or tetracaine. The synchrony of Ca2+ transients in capillary pericytes arising from spontaneous Ca2+ release from the sarco- and endoplasmic reticulum appears to rely exclusively on CaCC activation, whereas subsequent LVDCC activation is required for the synchrony of Ca2+ transients in pericytes of other microvascular segments. Capillary pericytes may drive spontaneous activity in the suburothelial microvascular unit to facilitate capillary perfusion.

Potential vascular mechanisms in an ex vivo functional pig bladder model.

AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase. Bladders were perfused at an initial flow rate of 20 mL/min and then clamped in a sequentially decreasing stepwise manner down to no flow and back to the initial flow rate. RESULTS: We found a linear relationship between flow rate and perfusion pressure until the flow rate decreased below 5 mL/min at which point the vascular resistance decreased; however, tissue pO2 remained stable after an initial decline. CONCLUSIONS: These findings suggest that there may be an intrinsic autoregulatory mechanism in the bladder that allows it to undergo cyclic episodes of relative ischemia during its normal function. Factors that overcome this mechanism such as complete or chronic ischemia may be critical in the progression to detrusor underactivity and thereby highlight the importance of intervention during the early phases of this disease process.