Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines

AbstractUrodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in animal models, especially cats (a common model of spinal cord injury and associated bladder pathology), anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select agents (dexmedetomidine, alfaxalone, propofol, isoflurane, and α-chloralose) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [ΔHR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.

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Role of Phosphodiesterase Inhibitors in Improving Urodynamic Parameters in Patients with Spinal Cord Injury: A Preliminary Report

Indian Journal of Neurosurgery ◽

10.1055/s-0040-1708571 ◽

2020 ◽

Vol 09 (01) ◽

pp. 30-34

Author(s):

Muzzain Iqbal ◽

Sarbjit Singh Chhiber ◽

Baldev Singh Wazir ◽

Altaf Umar Ramzan ◽

Mohammad Saleem Wani

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Oral Dose ◽

Single Oral Dose ◽

Bladder Capacity ◽

Final Conclusion ◽

Bladder Compliance ◽

Cord Injury ◽

Urodynamic Parameters

Abstract Objective To analyze role of phosphodiesterase 5 (PDE5) inhibitors on urodynamic parameters in patients with suprasacral spinal cord injury. Materials and Methods This was a prospective observational hospital-based study conducted on a cohort of patients, aged between 18 and 65 years with suprasacral spinal cord injury, who were registered in Department of Neurosurgery/Urology. Cutoff period since injury was 2 years. After taking consent, baseline urodynamic study was performed, which was repeated 2 hours after taking single oral dose of 20 mg tadalafil. Urodynamic parameters such as maximum detrusor filling/voiding pressures, maximum bladder capacity, and bladder compliance before and after taking drug were compared for final results and conclusion. Results Following administration of 20 mg of tadalafil, maximum bladder capacity in mL showed statistically significant improvement from 268.39 ± 130.0 to 298.55 ± 112.0.(p < 0.05). Bladder compliance improved from 18.68 ± 6.4 to 20.25 ± 7.5 mL/cm H2O (p > 0.05). Maximum detrusor filling pressure improved from 36.03 ± 20.54 to 32.90 ± 16.47 cm H2O (p > 0.05). Maximum detrusor voiding pressure improved from 64.65 ± 33.19 to 58.13 ± 20.7 cm H2O (0 > 0.05). In patients with injury above D6 spinal cord level, statistically significant improvement was seen in maximum bladder capacity and bladder compliance after 2 hours of single oral dose of tadalafil (p < 0.05). Conclusion Our study suggests a positive role of PDE inhibitors in improving urodynamic parameters in patients with suprasacral spinal cord injury with improvement in parameters such as bladder capacity, detrusor pressures, and bladder compliance. Because this is a small study group, more studies such as this are required to reach to final conclusion.

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Effects of Intravesical Prostaglandin E2 on Bladder Function are Preserved in Capsaicin-Desensitized Rats

AJP Renal Physiology ◽

10.1152/ajprenal.00302.2020 ◽

2020 ◽

Author(s):

James A. Hokanson ◽

Christopher L Langdale ◽

Philip H Milliken ◽

Arun Sridhar ◽

Warren M. Grill

Keyword(s):

Perfusion Pressure ◽

Bladder Capacity ◽

Female Rats ◽

Bladder Function ◽

Prostaglandin E ◽

Urethral Pressure ◽

Urinary Urgency ◽

Hypogastric Nerve ◽

C Fibers ◽

Bladder Compliance

Prostaglandin E2 (PGE2) instilled into the bladder generates symptoms of urinary urgency in healthy women and reduces bladder capacity and urethral pressure in both humans and female rats. Systemic capsaicin desensitization, which causes degeneration of C-fibers, prevented PGE2 mediated reductions in bladder capacity, suggesting that PGE2 acts as an irritant (Maggi et al.1988). In the present study, we instilled PGE2 in female rats after capsaicin desensitization, but without the hypogastric nerve transection that was conducted in the Maggi et al. study. One week after capsaicin injection (125 mg/kg, SC) rats underwent cystometric and urethral perfusion testing under urethane anesthesia with saline and 100 µM PGE2. Similar to naïve rats, capsaicin-desensitized rats exhibited a reduction in bladder capacity from 1.24 ± 0.13 ml to 0.70 ± 0.10 ml (P=0.002, n=9), a reduction in urethral perfusion pressure from 19.3 ± 2.1 cmH2O to 10.9 ± 1.15 cmH2O (P=0.004, n=9), and a reduction in bladder compliance from 0.13 ± 0.020 ml/cmH2O to 0.090 ± 0.014 ml/cmH2O (P=0.011, n=9). Thus, changes in bladder function following the instillationof PGE2 were not dependent on capsaicin-sensitive pathways. Further, these results suggest that urethral relaxation/weakness and/or increased detrusor pressure as a result of decreased compliance may contribute to urinary urgency and highlight potential targets for new therapies for overactive bladder.

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Urodynamic evaluation of patients with localized prostate cancer before and 4 months after robotic radical prostatectomy

Scientific Reports ◽

10.1038/s41598-021-83143-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dong Sup Lee ◽

Seung-ju Lee

Keyword(s):

Radical Prostatectomy ◽

Outlet Obstruction ◽

Maximum Flow ◽

Bladder Capacity ◽

Bladder Function ◽

Detrusor Contraction ◽

Bladder Compliance ◽

Urethral Closure ◽

Relative Change ◽

Urodynamic Parameters

AbstractRadical prostatectomy can alter the anatomy of the urinary bladder. We aimed to evaluate bladder function before and 4 months after radical prostatectomy using the urodynamic test and overactive bladder (OAB) symptom score. Among 70 prospectively enrolled patients, 61 patients completed the study. In the urodynamic test, bladder capacity and compliance did not change, the frequency of involuntary detrusor contraction decreased, the maximum flow rate and bladder outlet obstruction index improved, and the maximum urethral closure pressure (MUCP) deteriorated. Further evaluation of urodynamic parameters according to changes in symptoms was made. Although change in bladder compliance was correlated with changes in OAB symptoms, not the relative change of bladder compliance but the relative change in the MUCP was reliable factor when OAB symptoms were deteriorated. In general, prostatectomy did not deteriorate the condition of the detrusor; rather, change in the MUCP could be responsible for postprostatectomy OAB.

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Acute, severe traumatic spinal cord injury: improving urinary bladder function by optimizing spinal cord perfusion

Journal of Neurosurgery Spine ◽

10.3171/2021.3.spine202056 ◽

2021 ◽

pp. 1-8

Author(s):

Florence R. A. Hogg ◽

Siobhan Kearney ◽

Eskinder Solomon ◽

Mathew J. Gallagher ◽

Argyro Zoumprouli ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Urinary Bladder ◽

Perfusion Pressure ◽

Bladder Function ◽

Traumatic Spinal Cord Injury ◽

Injury Site ◽

Bladder Compliance ◽

Cord Injury

OBJECTIVE The authors sought to investigate the effect of acute, severe traumatic spinal cord injury on the urinary bladder and the hypothesis that increasing the spinal cord perfusion pressure improves bladder function. METHODS In 13 adults with traumatic spinal cord injury (American Spinal Injury Association Impairment Scale grades A–C), a pressure probe and a microdialysis catheter were placed intradurally at the injury site. We varied the spinal cord perfusion pressure and performed filling cystometry. Patients were followed up for 12 months on average. RESULTS The 13 patients had 63 fill cycles; 38 cycles had unfavorable urodynamics, i.e., dangerously low compliance (< 20 mL/cmH2O), detrusor overactivity, or dangerously high end-fill pressure (> 40 cmH2O). Unfavorable urodynamics correlated with periods of injury site hypoperfusion (spinal cord perfusion pressure < 60 mm Hg), hyperperfusion (spinal cord perfusion pressure > 100 mm Hg), tissue glucose < 3 mM, and tissue lactate to pyruvate ratio > 30. Increasing spinal cord perfusion pressure from 67.0 ± 2.3 mm Hg (average ± SE) to 92.1 ± 3.0 mm Hg significantly reduced, from 534 to 365 mL, the median bladder volume at which the desire to void was first experienced. All patients with dangerously low average initial bladder compliance (< 20 mL/cmH2O) maintained low compliance at follow-up, whereas all patients with high average initial bladder compliance (> 100 mL/cmH2O) maintained high compliance at follow-up. CONCLUSIONS We conclude that unfavorable urodynamics develop within days of traumatic spinal cord injury, thus challenging the prevailing notion that the detrusor is initially acontractile. Urodynamic studies performed acutely identify patients with dangerously low bladder compliance likely to benefit from early intervention. At this early stage, bladder function is dynamic and is influenced by fluctuations in the physiology and metabolism at the injury site; therefore, optimizing spinal cord perfusion is likely to improve urological outcome in patients with acute severe traumatic spinal cord injury.

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Pediatric Spine Surgery

10.1093/med/9780190850036.003.0016 ◽

2018 ◽

Author(s):

Abigail E. Meigh ◽

Ingrid A. Fitz-James Antoine ◽

Veronica Carullo

Keyword(s):

Spinal Cord ◽

Postoperative Pain ◽

Spinal Fusion ◽

Anesthetic Depth ◽

Neurologic Outcomes ◽

Anesthetic Agents ◽

Cord Injury ◽

Severe Postoperative Pain ◽

Substantial Risk ◽

Patients Experience

In children, the most common indication for spinal fusion is significant scoliotic curvature, either idiopathic or as a result of neuromuscular disease. Spinal fusion is high-risk surgery, which can be further complicated by comorbid disease. It carries substantial risk for significant fluid shifts, high intraoperative blood loss, physiologic strain secondary to duration and positioning, severe postoperative pain, and potential spinal cord injury. To mitigate risk and optimize outcomes, these patients should be carefully evaluated by the anesthetic team preoperatively and a comprehensive perioperative plan established. To protect the spinal cord and predict poor neurologic outcomes, the majority of these cases employ intraoperative neuromonitoring. The specific anesthetic agents to allow maximal neuromonitoring signals while ensuring adequate anesthetic depth and pain control should also be established collaboratively. These patients experience severe postoperative pain, and a multimodal approach to therapy should be employed to allow for expedited recovery and decreased length of stay.

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Combination of bladder ultrasonography and novel cystometry method in mice reveals rapid decrease in bladder capacity and compliance in LPS-induced cystitis

AJP Renal Physiology ◽

10.1152/ajprenal.00043.2014 ◽

2014 ◽

Vol 307 (2) ◽

pp. F234-F241 ◽

Cited By ~ 12

Author(s):

Kentaro Takezawa ◽

Makoto Kondo ◽

Hiroshi Kiuchi ◽

Tetsuji Soda ◽

Tetsuya Takao ◽

...

Keyword(s):

Bladder Dysfunction ◽

Bladder Wall ◽

Bladder Capacity ◽

Rapid Decrease ◽

Bladder Function ◽

Functional Changes ◽

Pressure Threshold ◽

Bladder Compliance ◽

Conventional Methods ◽

Voided Volume

Various animal models have been used in research into bladder dysfunction, and in vivo cystometry is a common method to analyze bladder function in animals. However, it is rather difficult to perform reliably in small animals. Transabdominal bladder ultrasonography combined with cystometry in urethane-anesthetized mice have revealed physical inhibition of bladder wall movement by a bladder catheter conventionally placed in the bladder apex. For reliable evaluation of mouse lower urinary tract function, we established a novel cystometry method in which a catheter was placed in the bladder anterior wall, in combination with bladder ultrasonography. This new method allowed the bladder to be well distended (i.e., larger maximum bladder capacity, lower pressure threshold, higher voided volume, and higher bladder compliance compared with conventional methods), which reflected more spontaneous voiding than conventional cystometry methods. We also demonstrated the usefulness of bladder ultrasonography for analysis of mouse bladder function, especially bladder dynamics, maximum bladder capacity, and post-voiding residual volume. We analyzed bladder functional changes in lipopolysaccharide (LPS)-induced cystitis by combining bladder ultrasonography and this new cystometry method. Bladder ultrasonography revealed a rapid decrease in bladder capacity, and cystometry showed a rapid decrease in voided volume due to intravesical LPS instillation. This new cystometry method also revealed a rapid decrease in bladder compliance caused by LPS instillation, which was not detectable by conventional methods. The combination of ultrasonography and the new cystometry method may become a powerful tool for analysis of mouse bladder function and could contribute to the development of new treatments for bladder dysfunction.

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THE EFFECT OF OXYBUTYNIN ON NEUROGENIC DETRUSOR OVERACTIVITY IN SPINAL CORD INJURY PATIENT: A HOSPITAL BASED INTERVENTIONAL STUDY

10.36106/pijr/8501736 ◽

2021 ◽

pp. 42-44

Author(s):

Vineet Bharti ◽

Nikhil Agarwal ◽

Mrinal Joshi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neurogenic Bladder ◽

Detrusor Overactivity ◽

Anticholinergic Drug ◽

Bladder Capacity ◽

Spinal Cord Injury Patient ◽

Detrusor Sphincter Dyssynergia ◽

Bladder Compliance ◽

Cord Injury

Neurogenic bladder dysfunction is one of prominent impairments following Spinal Cord Injury (SCI) and is seen in 90% of patients.This study has been undertaken to correlate the effect of anticholinergic drug (oxybutynin) on urodynamic parameters in neurogenic bladder of SCI patients.This is a hospital based non randomized prospective interventional study.After initial baseline urodynamic study,patients with detrusor areflexia were excluded from the study group and thirty patients showing detrusor overactivity and detrusor sphincter dyssynergia were treated with oral oxybutynin 5 mg for 7 days followed by repeat urodynamic evaluation thereafter.Our study concluded that mean bladder compliance improved from 6.114 to 17.95 ml/cmH2O after intervention and mean bladder capacity also increased after intervention (229.7ml) from (165.3ml) and changes were statistically significant.Antimuscarinic (Oxybutynin) is an effective drug in management of neurogenic bladder in SCI patients increases bladder compliance and capacity and results are objectively achieved within seven days

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An excitatory reflex from the superficial peroneal nerve to the bladder in cats

AJP Renal Physiology ◽

10.1152/ajprenal.00265.2017 ◽

2017 ◽

Vol 313 (5) ◽

pp. F1161-F1168 ◽

Cited By ~ 5

Author(s):

Michelle Yu ◽

Jamie Uy ◽

Xuewen Jiang ◽

Xing Li ◽

Cameron Jones ◽

...

Keyword(s):

Nerve Stimulation ◽

Peroneal Nerve ◽

Control Level ◽

Dorsal Surface ◽

Bladder Capacity ◽

Skin Surface ◽

Bladder Function ◽

Bladder Pressure ◽

Superficial Peroneal Nerve ◽

The Impact

This study in α-chloralose-anesthetized cats discovered an excitatory peroneal nerve-to-bladder reflex. A urethral catheter was used to infuse the bladder with saline and record bladder pressure changes. Electrical stimulation was applied to the superficial peroneal nerve to trigger reflex bladder activity. With the bladder distended at a volume ~90% of bladder capacity, superficial peroneal nerve stimulation (PNS) at 1–3 Hz and threshold (T) intensity for inducing muscle twitching on the posterior thigh induced large-amplitude (40–150 cmH2O) bladder contractions. PNS (1–3 Hz, 1–2T) applied during cystometrograms (CMGs) when the bladder was slowly (1–3 ml/min) infused with saline significantly ( P < 0.01) reduced bladder capacity to ~80% of the control capacity and significantly ( P < 0.05) enhanced reflex bladder contractions. To determine the impact of PNS on tibial nerve stimulation (TNS)-induced changes in bladder function, PNS was delivered following TNS. TNS of 30-min duration produced long-lasting poststimulation inhibition and significantly ( P < 0.01) increased bladder capacity to 140.5 ± 7.6% of the control capacity. During the post-TNS inhibition period, PNS (1–3 Hz, 1–4T) applied during CMGs completely restored bladder capacity to the control level and significantly ( P < 0.05) increased the duration of reflex bladder contractions to ~200% of control. The excitatory peroneal nerve-to-bladder reflex could also be activated by transcutaneous PNS using skin surface electrodes attached to the dorsal surface of the foot. These results raise the possibility of developing novel neuromodulation therapies to treat underactive bladder and nonobstructive urinary retention.

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Bladder pressure encoding by near-independent fibre subpopulations — implications for decoding

10.1101/826297 ◽

2019 ◽

Author(s):

Carl H. Lubba ◽

Zhonghua Ouyang ◽

Nick S. Jones ◽

Tim M. Bruns ◽

Simon R. Schultz

Keyword(s):

Information Theory ◽

Microelectrode Array ◽

Cell Loss ◽

Surrogate Data ◽

The Body ◽

Bladder Function ◽

Bladder Pressure ◽

Intravesical Pressure ◽

Cord Injury ◽

Encoding Strategies

AbstractObjectiveWe aim at characterising the encoding of bladder pressure (intravesical pressure) by a population of sensory fibres. This research is motivated by the possibility to restore bladder function in elderly patients or after spinal cord injury using implanted devices, so called bioelectronic medicines. For these devices, nerve-based estimation of intravesical pressure can enable a personalized and on-demand stimulation paradigm, which will be more effective and efficient. In this context, a better understanding of the encoding strategies employed by the body might in the future be exploited by informed decoding algorithms that enable a precise and robust bladderpressure estimation.ApproachTo this end, we apply information theory to microelectrode-array recordings from the cat sacral dorsal root ganglion while filling the bladder, conduct surrogate data studies to augment the data we have, and finally decode pressure in a simple informed approach.Main resultsWe find an encoding scheme by different main bladder neuron types that we divide into three response types (slow tonic, phasic, and derivative fibres). We show that an encoding by different bladder neuron types, each represented by multiple cells, offers reliability through within-type redundancy and high information rates through near-independence of different types. Our subsequent decoding study shows a potentially more robust decoding from mean responses of homogeneous cell pools.SignificanceWe have here, for the first time, analysed the encoding of intravesical pressure by a population of sensory neurons in a principled way using information theory. We show that even a simple adapted decoder can exploit the redundancy in the population to be more robust against cell loss. This work thus paves the way towards principled encoding studies in the periphery and towards a new generation of informed peripheral nerve decoders for bioelectronic medicines.

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Cardiovascular and Metabolic Responses to Electrical Stimulation-Induced Leg Exercise in Spinal Cord Injury

Methods of Information in Medicine ◽

10.1055/s-0038-1636852 ◽

1997 ◽

Vol 36 (04/05) ◽

pp. 372-375 ◽

Cited By ~ 9

Author(s):

J. R. Sutton ◽

A. J. Thomas ◽

G. M. Davis

Keyword(s):

Spinal Cord ◽

Heart Rate ◽

Spinal Cord Injury ◽

Cardiac Output ◽

Electrical Stimulation ◽

Knee Flexion ◽

Flexion Extension ◽

Cord Injury ◽

Leg Exercise ◽

Leg Muscle

Abstract:Electrical stimulation-induced leg muscle contractions provide a useful model for examining the role of leg muscle neural afferents during low-intensity exercise in persons with spinal cord-injury and their able-bodied cohorts. Eight persons with paraplegia (SCI) and 8 non-disabled subjects (CONTROL) performed passive knee flexion/extension (PAS), electrical stimulation-induced knee flexion/extension (ES) and voluntary knee flexion/extension (VOL) on an isokinetic dynamometer. In CONTROLS, exercise heart rate was significantly increased during ES (94 ± 6 bpm) and VOL (85 ± 4 bpm) over PAS (69 ± 4 bpm), but no changes were observed in SCI individuals. Stroke volume was significantly augmented in SCI during ES (59 ± 5 ml) compared to PAS (46 ± 4 ml). The results of this study suggest that, in able-bodied humans, Group III and IV leg muscle afferents contribute to increased cardiac output during exercise primarily via augmented heart rate. In contrast, SCI achieve raised cardiac output during ES leg exercise via increased venous return in the absence of any change in heart rate.

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