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Tim M Bruns - One of the best experts on this subject based on the ideXlab platform.
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urodynamic parameters and anesthetic depth vary depending on anesthetic agent alfaxalone dexmedetomidine propofol at doses necessary to facilitate preclinical testing
bioRxiv, 2019Co-Authors: Zuha Yousuf, Zhonghua Ouyang, Eric Kennedy, Patrick A Lester, Tara Martin, Tim M BrunsAbstract:Objectives: To compare the effects of select agents (dexmedetomidine, alfaxalone, propofol, isoflurane, and α-chloralose) on anesthetic and urodynamic parameters in felines. Materials and Methods: Adult male cats (n=5) were sedated at least three times per agent with dexmedetomidine (reversed with atipamezole), alfaxalone, and propofol on separate days, and anesthetized one time with isoflurane, then transitioned to α-chloralose during a terminal procedure. At least two cystometrograms (CMGs) were conducted in each sedated session. Urodynamic parameters (ΔPressure, Bladder capacity, Bladder compliance, non-voiding contractions, Bladder Pressure slopes) and anesthetic parameters (change in heart rate [ΔHR], average heart rate [HR], reflexes, induction/recovery times) were evaluated. Results: ΔPressure was greatest with propofol (117 ± 10 cm H20), Bladder capacity was highest with α-chloralose (60 ± 9 ml), non-voiding contractions (NVCs) were greatest with α-chloralose (0.03 ± 0.01 NVCs/s). Propofol and dexmedetomidine had the highest Bladder Pressure slopes during the initial and final portions of the CMGs respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine (HR 117 ± 6; ΔHR 19 ± 21 bpm), compared to propofol (HR 174 ± 6 bpm; ΔHR 85 ± 22 bpm) and alfaxalone (HR 211 ± 6 bpm; ΔHR 77 ± 21 bpm). Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. Conclusion: These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choice.
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closed loop control of sacral neuromodulation for Bladder function using dorsal root ganglia sensory feedback in an acute feline model
bioRxiv, 2019Co-Authors: Zhonghua Ouyang, Tim M BrunsAbstract:Overactive Bladder patients suffer from a frequent and uncontrollable urge to urinate, which can lead to a poor quality of life. Current sacral neuromodulation therapy uses open-loop electrical stimulation to alleviate symptoms, which limits battery life and can lead to neural habituation. In this study, we aim to improve therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 non-survival, anesthetized felines, in which the sacral-level DRG and spinal roots were exposed bilaterally. A bipolar cuff electrode was placed on a S1 root distal to the DRG for stimulation. Microelectrode arrays were implanted in the same or opposite S1 and/or S2 DRG. We implemented a Kalman filter-based algorithm to estimate the Bladder Pressure in real-time using DRG neural recordings. The Medtronic Summit Research Development Kit was used to control sacral root stimulation when the algorithm detected an increase in Bladder Pressure. Closed-loop neuromodulation was performed during continuous cystometry and compared to Bladder fills with continuous and no stimulation. Overall, closed-loop stimulation with DRG sensory feedback increased Bladder capacity by 13.8% over no stimulation (p
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closed loop control of sacral neuromodulation for Bladder function using dorsal root ganglia sensory feedback in an acute feline model
bioRxiv, 2019Co-Authors: Zhonghua Ouyang, Tim M BrunsAbstract:Overactive Bladder patients suffer from a frequent and uncontrollable urge to urinate, which can lead to a poor quality of life. Current sacral neuromodulation therapy uses open-loop electrical stimulation to alleviate symptoms, which limits battery life and can lead to neural habituation. In this study, we aim to improve therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 non-survival, anesthetized felines, in which the sacral-level DRG and spinal roots were exposed bilaterally. A bipolar cuff electrode was placed on a S1 root distal to the DRG for stimulation. Microelectrode arrays were implanted in the same or opposite S1 and/or S2 DRG. We implemented a Kalman filter-based algorithm to estimate the Bladder Pressure in real-time using DRG neural recordings. The Medtronic Summit Research Development Kit was used to control sacral root stimulation when the algorithm detected an increase in Bladder Pressure. Closed-loop neuromodulation was performed during continuous cystometry and compared to Bladder fills with continuous and no stimulation. Closed-loop stimulation with DRG sensory feedback reduced stimulation time by 57.7% compared to continuous, standard stimulation. Bladder capacity was increased by 13.8% over no stimulation and by 4.3% over continuous stimulation trials (p
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Evaluation of Decoding Algorithms for Estimating Bladder Pressure from Dorsal Root Ganglia Neural Recordings
Annals of Biomedical Engineering, 2018Co-Authors: Shani E. Ross, Zhonghua Ouyang, Sai Rajagopalan, Tim M BrunsAbstract:A closed-loop device for Bladder control may offer greater clinical benefit compared to current open-loop stimulation devices. Previous studies have demonstrated the feasibility of using single-unit recordings from sacral-level dorsal root ganglia (DRG) for decoding Bladder Pressure. Automatic online sorting, to differentiate single units, can be computationally heavy and unreliable, in contrast to simple multi-unit thresholded activity. In this study, the feasibility of using DRG multi-unit recordings to decode Bladder Pressure was examined. A broad range of feature selection methods and three algorithms (multivariate linear regression, basic Kalman filter, and a nonlinear autoregressive moving average model) were used to create training models and provide validation fits to Bladder Pressure for data collected in seven anesthetized feline experiments. A non-linear autoregressive moving average (NARMA) model with regularization provided the most accurate Bladder Pressure estimate, based on normalized root-mean-squared error, NRMSE, (17 ± 7%). A basic Kalman filter yielded the highest similarity to the Bladder Pressure with an average correlation coefficient, CC, of 0.81 ± 0.13. The best algorithm set (based on NRMSE) was further evaluated on data obtained from a chronic feline experiment. Testing results yielded a NRMSE and CC of 10.7% and 0.61, respectively from a model that was trained on data recorded 2 weeks prior. From offline analysis, implementation of NARMA in a closed-loop scheme for detecting Bladder contractions would provide a robust control signal. Ultimate integration of closed-loop algorithms in Bladder neuroprostheses will require evaluations of parameter and signal stability over time.
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chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface
Journal of Neural Engineering, 2017Co-Authors: Abeer Khurram, Shani E. Ross, Zachariah Sperry, Aileen Ouyang, Christopher Stephan, Ahmad A Jiman, Tim M BrunsAbstract:Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, Bladder neck and near the external urethral sphincter. Supra-pubic Bladder catheters were implanted for saline infusion and Pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and Bladder Pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4–11 weeks in four felines. As many as 18 unique Bladder Pressure single-units were identified in each experiment. Some channels consistently recorded Bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) Bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for Bladder control.
Osamu Nishizawa - One of the best experts on this subject based on the ideXlab platform.
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role of the β3 adrenoceptor in urine storage in the rat comparison between the selective β3 adrenoceptor agonist cl316 243 and various smooth muscle relaxants
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Hiroo Takeda, Yoshinobu Yamazaki, Masuo Akahane, Yasuhiko Igawa, Yukiyoshi Ajisawa, Osamu NishizawaAbstract:The objective of this study was to compare the effects of a β3-adrenoceptor (β3-AR) agonist on Bladder function and cardiovascular parameters in rats with those of several drugs that act on smooth muscle. CL316,243 (β3-AR agonist), isoproterenol (nonselective β-AR agonist), procaterol (β2-AR agonist), verapamil (Ca2+ antagonist), and papaverine (antispastic drug) each evoked a concentration-dependent relaxation of the detrusor in vitro. They also reduced Bladder Pressure in anesthetized rats, the β-AR agonists apparently being more potent than the other drugs. Atropine (muscarinic antagonist) neither relaxed detrusor strips nor reduced Bladder Pressure. In anesthetized rats, CL316,243 and atropine each had only a slight influence on blood Pressure and heart rate, but isoproterenol, procaterol, verapamil, and papaverine significantly affected cardiovascular function at the same dose range as that required to reduce Bladder Pressure. In cystometry experiments, CL316,243 (10 μg/kg i.v.), verapamil (1 mg/kg i.v.), and papaverine (1 mg/kg i.v.) all significantly prolonged micturition interval and increased Bladder capacity, but did not change the residual urine volume after a micturition contraction. Procaterol (100 μg/kg i.v.) prolonged the micturition interval and increased both Bladder capacity and residual urine volume (all significantly). Atropine (100 μg/kg i.v.) reduced micturition Pressure and increased residual urine volume (both significantly). Because the human detrusor, like the rat detrusor, relaxes on β3-AR stimulation, we conclude that this β3-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiovascular side effects.
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role of the beta 3 adrenoceptor in urine storage in the rat comparison between the selective beta 3 adrenoceptor agonist cl316 243 and various smooth muscle relaxants
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Hiroo Takeda, Yoshinobu Yamazaki, Masuo Akahane, Yasuhiko Igawa, Yukiyoshi Ajisawa, Osamu NishizawaAbstract:The objective of this study was to compare the effects of a beta(3)-adrenoceptor (beta(3)-AR) agonist on Bladder function and cardiovascular parameters in rats with those of several drugs that act on smooth muscle. CL316,243 (beta(3)-AR agonist), isoproterenol (nonselective beta-AR agonist), procaterol (beta(2)-AR agonist), verapamil (Ca(2+) antagonist), and papaverine (antispastic drug) each evoked a concentration-dependent relaxation of the detrusor in vitro. They also reduced Bladder Pressure in anesthetized rats, the beta-AR agonists apparently being more potent than the other drugs. Atropine (muscarinic antagonist) neither relaxed detrusor strips nor reduced Bladder Pressure. In anesthetized rats, CL316,243 and atropine each had only a slight influence on blood Pressure and heart rate, but isoproterenol, procaterol, verapamil, and papaverine significantly affected cardiovascular function at the same dose range as that required to reduce Bladder Pressure. In cystometry experiments, CL316,243 (10 microg/kg i.v.), verapamil (1 mg/kg i.v.), and papaverine (1 mg/kg i.v.) all significantly prolonged micturition interval and increased Bladder capacity, but did not change the residual urine volume after a micturition contraction. Procaterol (100 microg/kg i.v.) prolonged the micturition interval and increased both Bladder capacity and residual urine volume (all significantly). Atropine (100 microg/kg i.v.) reduced micturition Pressure and increased residual urine volume (both significantly). Because the human detrusor, like the rat detrusor, relaxes on beta(3)-AR stimulation, we conclude that this beta(3)-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiovascular side effects.
Margot S. Damaser - One of the best experts on this subject based on the ideXlab platform.
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Transurethral versus suprapubic catheterization to test urethral function in rats
'Springer Science and Business Media LLC', 2021Co-Authors: Kristine Janssen, Steve J. A. Majerus, Kangli Deng, Dan Li Lin, Brett Hanzlicek, Robert S. Butler, Carl H. Van Der Vaart, Margot S. DamaserAbstract:Abstract Transurethral and suprapubic catheterization have both been used to test urethral function in rats; however, it is unknown whether these methods affect urethral function or if the order of catheterization affects the results. The aim of this cross-over designed experiment was to compare the effects of catheterization methods and order on leak point Pressure (LPP) testing. LPP and simultaneous external urethral sphincter electromyography (EUS EMG) were recorded in anesthetized female virgin Sprague-Dawley rats in a cross-over design to test the effects of transurethral and suprapubic catheterization. There was no significant difference in peak Bladder Pressure during LPP testing whether measured with a transurethral or suprapubic catheter. There was no significant difference in peak Bladder Pressure between the first and second catheter insertions. However, peak EMG firing rate, as well as peak EMG amplitude and EMG amplitude difference between peak and baseline were significantly higher after the first catheter insertion compared to the second insertion, regardless of the catheter method. Our results suggest that route of catheterization does not alter urethral function, e.g. create a functional partial outlet obstruction. Either catheterization method could be used for LPP and/or EUS EMG testing in rats
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tunable and lightweight on chip event detection for implantable Bladder Pressure monitoring devices
IEEE Transactions on Biomedical Circuits and Systems, 2017Co-Authors: Robert Karam, Margot S. Damaser, Steve J. A. Majerus, Dennis Bourbeau, Swarup BhuniaAbstract:Lower urinary tract dysfunctions, such as urinary incontinence and overactive Bladder, are conditions that greatly affect the quality of life for millions of individuals worldwide. For those with more complex pathophysiologies, diagnosis of these conditions often requires a urodynamics study, providing physicians with a snapshot view of Bladder mechanics. Recent advancements in implantable Bladder Pressure monitors and advanced data analysis techniques have made diagnosis through chronic monitoring a promising prospect. However, implants targeted at treatment must remain in the Bladder for long periods of time, making minimizing power consumption a primary design objective. Currently, much of the typical implant's power draw is due to data transmission. Previous work has demonstrated an adaptive rate transmission technique to reduce power consumption. However, the ultimate reduction in power consumption can only be attained when the device does not transmit Bladder Pressure samples, but rather Bladder events . In this paper, we present an algorithm and circuit level implementation for on-chip Bladder Pressure data compression and event detection. It is designed to be a complete, tunable, and lightweight diagnosis and treatment framework for Bladder Pressure monitoring implants, capable of selectively transmitting compressed Bladder Pressure data with tunable quality, “snapshots” of significant Bladder events, or simply indicate events occurred for the highest energy efficiency. The design aims to minimize area through resource reuse, leading to a total area of 1.75 $\text{mm}^2$ , and employs advanced VLSI techniques for power reduction. With compression and event detection enabled, the design consumes roughly 2.6 nW in TSMC $\text{0.18}\text{-}\mu {\text m}$ technology. With only event detection, this reduces to 2.1 nW, making this approach ideal for long-life implantable Bladder Pressure monitoring devices.
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Wireless, Ultra-Low-Power Implantable Sensor for Chronic Bladder Pressure Monitoring
ACM Journal on Emerging Technologies in Computing Systems, 2012Co-Authors: Steve J. A. Majerus, Michael A Suster, Paul C. Fletter, Steven L. Garverick, Margot S. DamaserAbstract:The wireless implantable/intracavity micromanometer (WIMM) system was designed to fulfill the unmet need for a chronic Bladder Pressure sensing device in urological fields such as urodynamics for diagnosis and neuromodulation for Bladder control. Neuromodulation in particular would benefit from a wireless Bladder Pressure sensor which could provide real-time Pressure feedback to an implanted stimulator, resulting in greater Bladder capacity while using less power. The WIMM uses custom integrated circuitry, a MEMS transducer, and a wireless antenna to transmit Pressure telemetry at a rate of 10 Hz. Aggressive power management techniques yield an average current draw of 9 μA from a 3.6-Volt micro-battery, which minimizes the implant size. Automatic Pressure offset cancellation circuits maximize the sensing dynamic range to account for drifting Pressure offset due to environmental factors, and a custom telemetry protocol allows transmission with minimum overhead. Wireless operation of the WIMM has demonstrated that the external receiver can receive the telemetry packets, and the low power consumption allows for at least 24 hours of operation with a 4-hour wireless recharge session.
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Pelvic floor muscles and the external urethral sphincter have different responses to applied Bladder Pressure during continence
Urology, 2010Co-Authors: Hai-hong Jiang, Levilester Salcedo, Bo Song, Margot S. DamaserAbstract:Objectives To determine the functional innervation of the pelvic floor muscles (PFM) and whether there is PFM activity during an external Pressure increase to the Bladder in female rats. Methods Thirty-one female adult virgin Sprague–Dawley rats received an external increase in Bladder Pressure until urinary leakage was noted while Bladder Pressure was recorded (leak point Pressure [LPP]) under urethane anesthesia. Six of the rats underwent repeat LPP testing after bilateral transection of the levator ani nerve. Another 6 rats underwent repeat LPP testing after bilateral transection of the pudendal nerve. Simultaneous recordings of PFM (pubo- and iliococcygeus muscles), electromyogram (EMG), and external urethral sphincter (EUS) EMG were recorded during cystometry and LPP testing. Results Thirteen rats (42%) showed tonic PFM EMG activity during filling cystometry. Eighteen rats (58%) showed no tonic PFM EMG activity at baseline, but PFM EMG could be activated by pinching the perineal skin. This activity could be maintained unless voiding occurred. The external increase in Bladder Pressure caused significantly increased EUS EMG activity as demonstrated by increased amplitude and frequency. However, there was no such response in PFM EMG. LPP was not significantly different after levator ani nerve transection, but was significantly decreased after pudendal nerve transection. Conclusions PFM activity was not increased during external Pressure increases to the Bladder in female rats. Experimental designs using rats should consider this result. The PFM, unlike the EUS, does not contribute to the Bladder-to-urethra continence reflex. PFM strengthening may nonetheless facilitate urinary continence clinically by stabilizing the Bladder neck.
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urothelial biomechanics submucosal sensing of intravesical Pressure
ASME 2008 Summer Bioengineering Conference Parts A and B, 2008Co-Authors: Paul C. Fletter, Paul Zaszczurynski, Margot S. DamaserAbstract:Measurement of physiological Pressures is fundamental to many forms of medical diagnosis and monitoring in the cardiovascular, respiratory, gastrointestinal, urological and other systems. Pressure is usually measured via catheters, either connected to transducers outside the body or more recently by micro-transducers mounted on the tip of such catheters. However, this requires that the catheters be inserted and maintained without infection and that the patient be tethered to a recording device. While this may be manageable during short term tests such as urodynamics, the measurement of Bladder Pressure to diagnose incontinence, chronic monitoring poses an additional set of obstacles.Copyright © 2008 by ASME
Shani E. Ross - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of Decoding Algorithms for Estimating Bladder Pressure from Dorsal Root Ganglia Neural Recordings
Annals of Biomedical Engineering, 2018Co-Authors: Shani E. Ross, Zhonghua Ouyang, Sai Rajagopalan, Tim M BrunsAbstract:A closed-loop device for Bladder control may offer greater clinical benefit compared to current open-loop stimulation devices. Previous studies have demonstrated the feasibility of using single-unit recordings from sacral-level dorsal root ganglia (DRG) for decoding Bladder Pressure. Automatic online sorting, to differentiate single units, can be computationally heavy and unreliable, in contrast to simple multi-unit thresholded activity. In this study, the feasibility of using DRG multi-unit recordings to decode Bladder Pressure was examined. A broad range of feature selection methods and three algorithms (multivariate linear regression, basic Kalman filter, and a nonlinear autoregressive moving average model) were used to create training models and provide validation fits to Bladder Pressure for data collected in seven anesthetized feline experiments. A non-linear autoregressive moving average (NARMA) model with regularization provided the most accurate Bladder Pressure estimate, based on normalized root-mean-squared error, NRMSE, (17 ± 7%). A basic Kalman filter yielded the highest similarity to the Bladder Pressure with an average correlation coefficient, CC, of 0.81 ± 0.13. The best algorithm set (based on NRMSE) was further evaluated on data obtained from a chronic feline experiment. Testing results yielded a NRMSE and CC of 10.7% and 0.61, respectively from a model that was trained on data recorded 2 weeks prior. From offline analysis, implementation of NARMA in a closed-loop scheme for detecting Bladder contractions would provide a robust control signal. Ultimate integration of closed-loop algorithms in Bladder neuroprostheses will require evaluations of parameter and signal stability over time.
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chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface
Journal of Neural Engineering, 2017Co-Authors: Abeer Khurram, Shani E. Ross, Zachariah Sperry, Aileen Ouyang, Christopher Stephan, Ahmad A Jiman, Tim M BrunsAbstract:Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, Bladder neck and near the external urethral sphincter. Supra-pubic Bladder catheters were implanted for saline infusion and Pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and Bladder Pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4–11 weeks in four felines. As many as 18 unique Bladder Pressure single-units were identified in each experiment. Some channels consistently recorded Bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) Bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for Bladder control.
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hysteretic behavior of Bladder afferent neurons in response to changes in Bladder Pressure
BMC Neuroscience, 2016Co-Authors: Shani E. Ross, Zachariah J Sperry, Colin Mahar, Tim M BrunsAbstract:Mechanosensitive afferents innervating the Bladder increase their firing rate as the Bladder fills and Pressure rises. However, the relationship between afferent firing rates and intravesical Pressure is not a simple linear one. Firing rate responses to Pressure can differ depending on prior activity, demonstrating hysteresis in the system. Though this hysteresis has been commented on in published literature, it has not been quantified. Sixty-six Bladder afferents recorded from sacral dorsal root ganglia in five alpha-chloralose anesthetized felines were identified based on their characteristic responses to Pressure (correlation coefficient ≥ 0.2) during saline infusion (2 ml/min). For saline infusion trials, we calculated a maximum hysteresis ratio between the firing rate difference at each Pressure and the overall firing rate range (or Hmax) of 0.86 ± 0.09 (mean ± standard deviation) and mean hysteresis ratio (or Hmean) of 0.52 ± 0.13 (n = 46 afferents). For isovolumetric trials in two experiments (n = 33 afferents) Hmax was 0.72 ± 0.14 and Hmean was 0.40 ± 0.14. A comprehensive state model that integrates these hysteresis parameters to determine the Bladder state may improve upon existing neuroprostheses for Bladder control.
Hiroo Takeda - One of the best experts on this subject based on the ideXlab platform.
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role of the β3 adrenoceptor in urine storage in the rat comparison between the selective β3 adrenoceptor agonist cl316 243 and various smooth muscle relaxants
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Hiroo Takeda, Yoshinobu Yamazaki, Masuo Akahane, Yasuhiko Igawa, Yukiyoshi Ajisawa, Osamu NishizawaAbstract:The objective of this study was to compare the effects of a β3-adrenoceptor (β3-AR) agonist on Bladder function and cardiovascular parameters in rats with those of several drugs that act on smooth muscle. CL316,243 (β3-AR agonist), isoproterenol (nonselective β-AR agonist), procaterol (β2-AR agonist), verapamil (Ca2+ antagonist), and papaverine (antispastic drug) each evoked a concentration-dependent relaxation of the detrusor in vitro. They also reduced Bladder Pressure in anesthetized rats, the β-AR agonists apparently being more potent than the other drugs. Atropine (muscarinic antagonist) neither relaxed detrusor strips nor reduced Bladder Pressure. In anesthetized rats, CL316,243 and atropine each had only a slight influence on blood Pressure and heart rate, but isoproterenol, procaterol, verapamil, and papaverine significantly affected cardiovascular function at the same dose range as that required to reduce Bladder Pressure. In cystometry experiments, CL316,243 (10 μg/kg i.v.), verapamil (1 mg/kg i.v.), and papaverine (1 mg/kg i.v.) all significantly prolonged micturition interval and increased Bladder capacity, but did not change the residual urine volume after a micturition contraction. Procaterol (100 μg/kg i.v.) prolonged the micturition interval and increased both Bladder capacity and residual urine volume (all significantly). Atropine (100 μg/kg i.v.) reduced micturition Pressure and increased residual urine volume (both significantly). Because the human detrusor, like the rat detrusor, relaxes on β3-AR stimulation, we conclude that this β3-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiovascular side effects.
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role of the beta 3 adrenoceptor in urine storage in the rat comparison between the selective beta 3 adrenoceptor agonist cl316 243 and various smooth muscle relaxants
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Hiroo Takeda, Yoshinobu Yamazaki, Masuo Akahane, Yasuhiko Igawa, Yukiyoshi Ajisawa, Osamu NishizawaAbstract:The objective of this study was to compare the effects of a beta(3)-adrenoceptor (beta(3)-AR) agonist on Bladder function and cardiovascular parameters in rats with those of several drugs that act on smooth muscle. CL316,243 (beta(3)-AR agonist), isoproterenol (nonselective beta-AR agonist), procaterol (beta(2)-AR agonist), verapamil (Ca(2+) antagonist), and papaverine (antispastic drug) each evoked a concentration-dependent relaxation of the detrusor in vitro. They also reduced Bladder Pressure in anesthetized rats, the beta-AR agonists apparently being more potent than the other drugs. Atropine (muscarinic antagonist) neither relaxed detrusor strips nor reduced Bladder Pressure. In anesthetized rats, CL316,243 and atropine each had only a slight influence on blood Pressure and heart rate, but isoproterenol, procaterol, verapamil, and papaverine significantly affected cardiovascular function at the same dose range as that required to reduce Bladder Pressure. In cystometry experiments, CL316,243 (10 microg/kg i.v.), verapamil (1 mg/kg i.v.), and papaverine (1 mg/kg i.v.) all significantly prolonged micturition interval and increased Bladder capacity, but did not change the residual urine volume after a micturition contraction. Procaterol (100 microg/kg i.v.) prolonged the micturition interval and increased both Bladder capacity and residual urine volume (all significantly). Atropine (100 microg/kg i.v.) reduced micturition Pressure and increased residual urine volume (both significantly). Because the human detrusor, like the rat detrusor, relaxes on beta(3)-AR stimulation, we conclude that this beta(3)-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiovascular side effects.