Current evidence regarding alternative techniques for enterocystoplasty using regenerative medicine methods: a systematic review.

Enterocystoplasty is the most commonly used treatment for bladder reconstruction. However, it has some major complications. In this study, we systematically reviewed the alternative techniques for enterocystoplasty using different scaffolds. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library, and a total of 10 studies were included in this study. Five different scaffolds were evaluated, including small intestinal submucosa (SIS), biodegradable scaffolds seeded with autologous bladder muscle and urothelial cells, dura mater, human cadaveric bladder acellular matrix graft, and bovine pericardium. The overall results revealed that bladder reconstruction using regenerative medicine is an excellent alternative method to enterocystoplasty regarding the improvement of bladder capacity, bladder compliance, and maximum detrusor pressure; however, more large-scale studies are required.

PTHrP attenuates spontaneous contractions in detrusor smooth muscle of the rat bladder by activating spontaneous transient outward potassium currents.

Parathyroid hormone-related protein (PTHrP) released from detrusor smooth muscle (DSM) cells upon bladder distension attenuates spontaneous phasic contractions (SPCs) in DSM and associated afferent firing to facilitate urine storage. Here, we investigate the mechanisms underlying PTHrP-induced inhibition of SPCs, focusing on large-conductance Ca2+-activated K+ channels (BK channels) that play a central role in stabilizing DSM excitability. Perforated patch-clamp techniques were applied to DSM cells of the rat bladder dispersed using collagenase. Isometric tension changes were recorded from DSM strips, while intracellular Ca2+ dynamics were visualized using Cal520 AM -loaded DSM bundles. DSM cells developed spontaneous transient outward potassium currents (STOCs) arising from the opening of BK channels. PTHrP (10 nM) increased the frequency of STOCs without affecting their amplitude at a holding potential of - 30 mV but not - 40 mV. PTHrP enlarged depolarization-induced, BK-mediated outward currents at membrane potentials positive to + 20 mV in a manner sensitive to iberiotoxin (100 nM), the BK channel blocker. The PTHrP-induced increases in BK currents were also prevented by inhibitors of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) (CPA 10 µM), L-type voltage-dependent Ca2+ channel (LVDCC) (nifedipine 3 µM) or adenylyl cyclase (SQ22536 100 µM). PTHrP had no effect on depolarization-induced LVDCC currents. PTHrP suppressed and slowed SPCs in an iberiotoxin (100 nM)-sensitive manner. PTHrP also reduced the number of Ca2+ spikes during each burst of spontaneous Ca2+ transients. In conclusion, PTHrP accelerates STOCs discharge presumably by facilitating SR Ca2+ release which prematurely terminates Ca2+ transient bursts resulting in the attenuation of SPCs.

Real-time prediction of bladder urine leakage using fuzzy inference system and dual Kalman filtering in cats.

The use of electrical stimulation devices to manage bladder incontinence relies on the application of continuous inhibitory stimulation. However, continuous stimulation can result in tissue fatigue and increased delivered charge. Here, we employ a real-time algorithm to provide a short-time prediction of urine leakage using the high-resolution power spectrum of the bladder pressure during the presence of non-voiding contractions (NVC) in normal and overactive bladder (OAB) cats. The proposed method is threshold-free and does not require pre-training. The analysis revealed that there is a significant difference between voiding contraction (VC) and NVC pressures as well as band powers (0.5-5 Hz) during both normal and OAB conditions. Also, most of the first leakage points occurred after the maximum VC pressure, while all of them were observed subsequent to the maximum VC spectral power. Kalman-Fuzzy method predicted urine leakage on average 2.2 s and 1.6 s before its occurrence and an average of 2.0 s and 1.1 s after the contraction started with success rates of 94.2% and 100% in normal and OAB cats, respectively. This work presents a promising approach for developing a neuroprosthesis device, with on-demand stimulation to control bladder incontinence.

Vagal afferent responses to cystometry in rat models of urinary bladder irritation: c-fos immunohistochemistry study.

PURPOSE: Although recent literature provides increasing evidence concerning urinary bladder innervation by vagal afferents, the functional aspects and the conditions at which these afferents are recruited are still unclear. METHODS: In the present study, the neuronal responses of nodose ganglion following cystometry, under different models of rat's urinary bladder irritation, cyclophosphamide (CYP), cyclophosphamide with cervical vagotomy (Vx), chronic HCl, and acute HCl, were investigated using c-fos immunohistochemistry. RESULTS: The c-fos expression in the nodose ganglion, following cystometry, was increased significantly in the CYP and chronic-HCl groups compared to the intact, Vx, and acute-HCl groups. In addition, the acute-HCl group showed a significant increase compared to intact animals. Following cervical vagotomy, the expression in the Vx group decreased significantly compared to the CYP group, but was significantly higher than that in the intact group. CONCLUSION: The results of this study demonstrate the innervation of the vagus afferents to the urinary bladder. This innervation is activated under urinary bladder irritation conditions, which may indicate a possible role of the vagus nerve during urinary bladder pathology.

Extracellular nucleotides in smooth muscle contraction.

Extracellular nucleotides and nucleosides are crucial signalling molecules, eliciting diverse biological responses in almost all organs and tissues. These molecules exert their effects by activating specific nucleotide receptors, which are finely regulated by ectonucleotidases that break down their ligands. In this comprehensive review, we aim to elucidate the relevance of extracellular nucleotides as signalling molecules in the context of smooth muscle contraction, considering the modulatory influence of ectonucleotidases on this intricate process. Specifically, we provide a detailed examination of the involvement of extracellular nucleotides in the contraction of non-vascular smooth muscles, including those found in the urinary bladder, the airways, the reproductive system, and the gastrointestinal tract. Furthermore, we present a broader overview of the role of extracellular nucleotides in vascular smooth muscle contraction.

A Multielectrode Nerve Cuff for Chronic Velocity Selective Recording in a sheep model.

Supra-sacral spinal cord injury (SCI) causes loss of bladder fullness sensation and bladder over-activity, leading to retention and incontinence respectively. Velocity selective recording (VSR) of nerve roots innervating the bladder might enable identification of bladder activity. A 10-electrode nerve cuff for sacral nerve root VSR was developed and tested in a sheep model during acute surgeries and chronic implantation for 6 months. The cuff performed well, with 5.90±1.90 kΩ electrode, and <~800 Ω tissue impedance after 189 days implantation with a stable device and tissues. This is important information for assessing the feasibility of chronic VSR.Clinical Relevance-This demonstrates the manufacturing and performance of a neural interface for chronic monitoring of bladder nerve afferents with applications in urinary incontinence and retention management following SCI.

H2O2 enhances the spontaneous phasic contractions of isolated human-bladder strips via activation of TRPA1 channels on sensory nerves and the release of substance P and PGE2.

Several studies have indicated that reactive oxygen species (ROS) can lead to detrusor overactivity (DO), but the underlying mechanisms are not known. Hydrogen dioxide (H2O2) is used commonly to investigate the effects of ROS. In present study, we investigated the effects of H2O2 on phasic spontaneous bladder contractions (SBCs) of isolated human-bladder strips (iHBSs) and the underlying mechanisms. Samples of bladder tissue were obtained from 26 patients undergoing cystectomy owing to bladder cancer. SBCs of iHBSs were recorded in organ-bath experiments. H2O2 (1µM-10mM) concentration-dependently increased the SBCs of iHBSs. These enhancing effects could be mimicked by an agonist of transient receptor potential (TRP)A1 channels (allyl isothiocyanate) and blocked with an antagonist of TRPA1 channels (HC030031; 10 µM). H2O2 induced enhancing effects also could be attenuated by desensitizing sensory afferents with capsaicin (10 µM), blocking nerve firing with TTX (1 µM), blocking neurokinin effects with NK2 receptor antagonist (SR48968, 10 µM), and blocking PGE2 synthesis with indomethacin (10 µM), respectively. Our study: (i) suggests activation of TRPA1 channels on bladder sensory afferents, and then release of substance P or PGE2 from sensory nerve terminals, contribute to the H2O2-induced enhancing effects on SBCs of iHBSs; (ii) provides insights for the mechanisms underlying ROS leading to DO; (iii) indicates that targeting TRPA1 channels might be the promising strategy against overactive bladder in conditions associated with excessive production of ROS.

Pharmacological Studies on the Ca2+ Influx Pathways in Platelet-Activating Factor (PAF)-Induced Mouse Urinary Bladder Smooth Muscle Contraction.

Platelet-activating factor (PAF) not only acts as a mediator of platelet aggregation, inflammation, and allergy responses but also as a constrictor of various smooth muscle (SM) tissues, including gastrointestinal, tracheal/bronchial, and pregnancy uterine SMs. Previously, we reported that PAF induces basal tension increase (BTI) and oscillatory contraction (OC) in mouse urinary bladder SM (UBSM). In this study, we examined the Ca2+ influx pathways involved in PAF-induced BTI and OC in the mouse UBSM. PAF (10-6 M) induced BTI and OC in mouse UBSM. However, the PAF-induced BTI and OC were completely suppressed by extracellular Ca2+ removal. PAF-induced BTI and OC frequencies were markedly suppressed by voltage-dependent Ca2+ channel (VDCC) inhibitors (verapamil (10-5 M), diltiazem (10-5 M), and nifedipine (10-7 M)). However, these VDCC inhibitors had a minor effect on the PAF-induced OC amplitude. The PAF-induced OC amplitude in the presence of verapamil (10-5 M) was strongly suppressed by SKF-96365 (3 × 10-5 M), an inhibitor of receptor-operated Ca2+ channel (ROCC) and store-operated Ca2+ channel (SOCC), but not by LOE-908 (3 × 10-5 M) (an inhibitor of ROCC). Overall, PAF-induced BTI and OC in mouse UBSM depend on Ca2+ influx and the main Ca2+ influx pathways in PAF-induced BTI and OC may be VDCC and SOCC. Of note, VDCC may be involved in PAF-induced BTI and OC frequency, and SOCC might be involved in PAF-induced OC amplitude.

[Analysis of surgical complications of reconstructive plastic surgery according to the ClavienDindo classification].

INTRODUCTION: The systematization of surgical complications has long been a serious problem since different types of surgical procedures have specific complications, in addition to general consequences. Created in 1992 and improved in 2004, the Clavien-Dindo classification was successfully validated in surgical centers in different countries and recognized as an important tool for the qualitative assessment of surgical complications. AIM: To improve reconstructive procedures by systematizing complications based on the ClavienDindo classification. MATERIALS AND METHODS: The results of substitution ileocystoplasty in 95 patients with contracted bladder due to tuberculosis and other diseases are presented. In 50 (52.6%) cases, the length of the bowel segment was 30-35 cm (group 1, main), while in 45 patients (47.4%) a segment of 45-60 cm was chosen (group 2, control). RESULTS: Early complications of grade II developed in 11 (22.0%) patients in the group 1 and in 13 (28.9%) in group 2, while grade III in 5 (10.0%) and 6 (13.3%) cases, respectively. Complications of IIIb grade were seen among patients of the main group in 9 (18.0%) cases compared to 12 (26.7%) in the control group. Severe complications of IVa and IVb grades were documented with the same frequency in both groups, in one case each. Complications of V grade (death) were recorded only in the group 2. Late complications were registered in 63 out of 94 patients. In group 1, there were 26 complications (16 somatic and 10 surgical), while in group 2, a total of 37 complications (24 somatic and 13 surgical) were seen, which indicates a significant higher rate in the control group (p<0.05). In group 1, transurethral resection of urethral-enteric anastomosis and ureteral reimplantation were performed less frequently than in group 2, while transurethral resection of the prostate was done with the same frequency. At the same time, percutaneous nephrostomy was required more often in the group 1 (6% vs. 4.5% in the group 2). After intestinal cystoplasty with a shortened fragment of the ileum, the voiding volume was significantly lower but corresponded to the physiological value (more than 150 ml). In this group, there was sufficient capacity of neobladder with a minimum amount of residual urine, effective emptying, satisfactory urinary continence, and low intraluminal pressure, which contributes to the protection of kidneys from reservoir-ureteral-pelvic reflux. The serum chloride level after surgery was 106.2+/-0.4 in the group 1 compared to 109.7+/-0.3 in the group 2, while base excess was -0.93+/-0.3 and -3.4+/-0.65, respectively (p<0.05). CONCLUSION: Early serious postoperative complications according to Clavien-Dindo were registered with approximately the same frequency in both groups, while late complications developed significantly more often in the group 2. The urodynamic parameters of a neobladder formed from ileum segment of 30-35 cm are satisfactory. In addition, a decrease in the length of the intestinal segment prevents the development of hyperchloremic metabolic acidosis.

Effects of swelling and anatomical location on the viscoelastic behavior of the porcine urinary bladder wall.

The ability of the urinary bladder to perform its physiological function depends largely on its mechanical characteristics. Understanding the mechanics of this tissue is crucial to the development of accurate models of not just this specific organ, but of the pelvic floor overall. In this study, we tested porcine bladder to identify variations in the tissue's viscoelastic characteristics associated with anatomical locations and swelling. We investigated this relationship using a series of stress-relaxation experiments as well as a modified Maxwell-Wiechert model to aid in the interpretation of the experimental data. Our results highlight that tissue located near the neck of the bladder presents significantly different viscoelastic characteristics than the body of the organ. This supports what was previously observed and is a valuable contribution to the understanding of the location-specific properties of the bladder. We also tested the effect of swelling, revealing that the bladder's viscoelastic behavior is mostly independent of solution osmolarity in hypoosmotic solutions, but the use of a hyperosmotic solution can significantly affect its behavior. This is significant, since several urinary tract pathologies can lead to chronic inflammation and disrupt the urothelial barrier causing increased urothelial permeability, thus subjecting the bladder wall to non-physiologic osmotic challenge.

Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.

This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder-urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.

Application of Machine Learning Algorithms to the Discretization Problem in Wearable Electrical Tomography Imaging for Bladder Tracking.

The article presents the implementation of artificial intelligence algorithms for the problem of discretization in Electrical Impedance Tomography (EIT) adapted for urinary tract monitoring. The primary objective of discretization is to create a finite element mesh (FEM) classifier that will separate the inclusion elements from the background. In general, the classifier is designed to detect the area of elements belonging to an inclusion revealing the shape of that object. We show the adaptation of supervised learning methods such as logistic regression, decision trees, linear and quadratic discriminant analysis to the problem of tracking the urinary bladder using EIT. Our study focuses on developing and comparing various algorithms for discretization, which perfectly supplement methods for an inverse problem. The innovation of the presented solutions lies in the originally adapted algorithms for EIT allowing for the tracking of the bladder. We claim that a robust measurement solution with sensors and statistical methods can track the placement and shape change of the bladder, leading to effective information about the studied object. This article also shows the developed device, its functions and working principle. The development of such a device and accompanying information technology came about in response to particularly strong market demand for modern technical solutions for urinary tract rehabilitation.

Real-Time Void Spot Assay.

Normal voiding behavior is the result of the coordinated function of the bladder, the urethra, and the urethral sphincters under the proper control of the nervous system. To study voluntary voiding behavior in mouse models, researchers have developed the void spot assay (VSA), a method that measures the number and area of urine spots deposited on a filter paper lining the floor of an animal's cage. Although technically simple and inexpensive, this assay has limitations when used as an end-point assay, including a lack of temporal resolution of voiding events and difficulties quantifying overlapping urine spots. To overcome these limitations, we developed a video-monitored VSA, which we call real-time VSA (RT-VSA), and which allows us to determine voiding frequency, assess voided volume and voiding patterns, and make measurements over 6 h time windows during both the dark and light phases of the day. The method described in this report can be applied to a wide variety of mouse-based studies that explore the physiological and neurobehavioral aspects of voluntary micturition in health and disease states.

Simulation of the female pelvic mobility and vesical pressure changes employing fluid-structure interaction method.

INTRODUCTION AND HYPOTHESIS: This study aims to develop a fluid-structural interaction (FSI) method to pinpoint the effects of pressure changes inside the bladder and their impact on the supporting structure and the urethra mobility. METHODS: A physiological model of the nulliparous female pelvis, including the organs, supportive structures, and urine, was developed based on magnetic resonance images. Soft tissues with nonlinear hyperelastic material characteristics were modeled. The Navier-Stokes equations governing the fluid flow within the computational domain (urine) were solved. The urine and soft tissue interactions were simulated by the FSI method. The vesical pressure and its impact on the urethral mobility and supportive structures were investigated during the Valsalva maneuver. Moreover, the simulation results were validated by comparing with a urodynamic test and other research. RESULTS: The results demonstrated that the vesical pressure simulated by the FSI method could predict the nonlinear behavior of the urodynamic test pressure. The urethra retropubic bladder neck and the bladder neck-pubic bone angle changed 58.92% and -55.76%, respectively. The retropubic urethral length distance changed by -48.74%. The error compared to the statistical results of other research is < 5%. CONCLUSIONS: The total deformation and mobility of the urethra predicted by the FSI model were consistent with clinical observations in a subject. The urethra supports dependence on the tissues' mechanical properties, interaction between the tissues, and effect of urine fluid inside the bladder. This simulation effectively depicts the patterns of urethra mobility, which provides a better understanding of the behavior of the pelvic floor.

Prolonged inhibition of bladder function is evoked by low-amplitude electrical stimulation of the saphenous nerve in urethane-anesthetized rats.

To better understand the effects of saphenous nerve (SN) stimulation on bladder function, we investigated the duration of electrical stimulation as a key variable in eliciting urodynamic changes. SN stimulation is a novel approach to electrically modulating bladder function. In previous animal studies, bladder-inhibitory responses were evoked by low-amplitude (25 µA) stimulus pulses applied in short-duration (10 min) trials and at frequencies between 10 and 20 Hz. Experiments were performed in urethane-anesthetized rats that were separated into three groups: intravesical saline infusion + SN stimulation (group A), intravesical 0.1% acetic acid infusion + SN stimulation (group B), and intravesical saline infusion + no SN stimulation (group C). Changes in bladder function- basal bladder pressure (P base ), contraction amplitude (ΔP), and inter-contraction interval (T ICI )-were measured in response to stimulation trials applied for different durations (10, 20, and 40 min). Trials were also repeated at frequencies of 10 and 20 Hz. In group A, longer-duration (40 min) stimulation trials applied at 10 Hz evoked overflow incontinence (OI) episodes that were characterized by significant changes in P base (122.7 ± 9.1%, p = 0.026), ΔP (-60.8 ± 12.8%, p = 0.044), and T ICI (-43.2 ± 13.0%, p = 0.031). Stimulation-evoked OI was observed in 5 of 8 animals and lasted for 56.5 ± 10.7 min. In contrast, no significant changes in bladder function were observed in either group B or group C. Our findings show that longer-duration trials consisting of electrical pulses applied at 10 Hz are important stimulation parameters that elicit inhibitory bladder responses in anesthetized rodents.

In Vivo Luminal Measurement of Distension-evoked Urothelial ATP Release in Rodents.

ATP, released from the urothelium in response to bladder distension, is thought to play a significant sensory role in the control of micturition. Therefore, accurate measurement of urothelial ATP release in a physiological setting is an important first step in studying the mechanisms that control purinergic signaling in the urinary bladder. Existing techniques to study mechanically evoked urothelial ATP release utilize cultured cells plated on flexible supports or bladder tissue pinned into Ussing chambers; however, each of these techniques does not fully emulate conditions in the intact bladder. Therefore, an experimental setup was developed to directly measure ATP concentrations in the lumen of the rodent urinary bladder. In this setup, the bladders of anesthetized rodents are perfused through catheters in both the dome of the bladder and via the external urethral orifice. Pressure in the bladder is increased by capping the urethral catheter while perfusing sterile fluid into the bladder through the dome. Measurement of intravesical pressure is achieved using a pressure transducer attached to the bladder dome catheter, akin to the setup used for cystometry. Once the desired pressure is reached, the urethral catheter's cap is removed, and fluid collected for ATP quantification by luciferin-luciferase assay. Through this experimental setup, the mechanisms controlling both mechanical and chemical stimulation of urothelial ATP release can be interrogated by including various agonists or antagonists into the perfusate or by comparing results between wildtype and genetically modified animals.

An Open-source Computational Model of Neurostimulation of the Spinal Pudendo-Vesical Reflex for the Recovery of Bladder Control After Spinal Cord Injury.

Spinal cord stimulation (SCS) could be used to restore control of the bladder after spinal cord injury, but substantial development is still required to tailor this technology for bladder function. Computational models could be utilized to accelerate these efforts enabling in-silico optimization of stimulation parameters. However, no model of the spinal pudendo-vesical reflex can simulate the effect of stimulation amplitude on neuron recruitment. This limitation hinders accurate prediction of bladder pressure changes for different stimulation configurations. Here., we implemented an open-source realistic spiking neural network model of the pudendo-vesical reflex enabling exploration of the impact of stimulation amplitude and frequency on bladder pressure changes. We used the o2S2 PARC platform to design a parallel implementation of the bladder reflex circuits with NEURON. Our model successfully reproduced and expanded previous studies., producing a decrease in bladder pressure at low stimulation frequency (10 Hz) and excitation at high stimulation frequency (≥33 Hz) in isovolumetric experiments. We then explored the effect of mixed nerve recruitment., simulating a common case of poorly selective spinal cord stimulation. We found that high recruitments of pudendal nerve axons are necessary to maintain this bi-modal behavior., regardless of stimulation specificity. Our framework is fully open-source and can be used to simulate any type of axon stimulations such as SCS and peripheral nerve stimulation.

A Computational Study of Lower Urinary Tract Nerve Recruitment with Epidural Stimulation of the Lumbosacral Spinal Cord.

Bladder dysfunction is a major health risk for people with spinal cord injury. Recently, we have demonstrated that epidural sacral spinal cord stimulation (SCS) can be used to activate lower urinary tract nerves and provide both major components of bladder control: voiding and continence. To effectively control these functions, it is necessary to selectively recruit the afferents of the pudendal nerve that evoke these distinct bladder reflexes. Translation of this innovation to clinical practice requires an understanding of optimal electrode placements and stimulation parameters to guide surgical practice and therapy design. Computational modeling is an important tool to address many of these experimentally intractable stimulation optimization questions. Here, we built a realistic MRI-based finite element computational model of the feline sacral spinal cord which included realistic axon trajectories in the dorsal and ventral roots. We coupled the model with biophysical simulations of membrane dynamics of afferent and efferent axons that project to the lower urinary tract through the pelvic and pudendal nerves. We simulated the electromagnetic fields arising from stimulation through SCS electrodes and calculated the expected recruitment of pelvic and pudendal fibers. We found that SCS can selectively recruit pudendal afferents, in agreement with our experimental data in cats. Our results suggest that SCS is a promising technology to improve bladder function after spinal cord injury, and computational modeling unlocks the potential for highly optimized, selective stimulation. Clinical Relevance - This model provides a method to non-invasively establish electrode placement and stimulation parameters for improving bladder function with epidural spinal cord stimulation.

Canine Smooth Muscle Contraction Model.

Smooth muscle is found extensively in the human body, including in blood vessels, airways, the gastrointestinal tract, and the urinary bladder. Although the contractile proteins of smooth muscle are very similar to those of striated muscle, smooth muscle's contractile mechanism has not been studied as extensively as those for cardiac and skeletal muscle. Previous studies developed a lumped model of muscle contraction and applied it to cardiac muscle and to skeletal muscle. In this study, this model is used to quantitatively describe the contractile properties of canine smooth muscle, using data from the literature. Results show that a single equation relating muscle force to muscle length and time, and a single set of model parameters, is able to describe smooth muscle's passive and active isometric forces, isometric twitch contractions, isotonic contractions, and an inverse force-velocity relation. The latter arises from the model without assumption of a particular force-velocity curve embodied as a contractile element. This new constitutive relation may be used to describe smooth muscle within larger physiological models, for instance to describe blood vessel constriction or urinary bladder function.