Narendra Bhadra

High frequency electrical conduction block of the pudendal nerve

A reversible electrical block of the pudendal nerves may provide a valuable method for restoration of urinary voiding in individuals with bladder-sphincter dyssynergia. This study quantified the stimulus parameters and effectiveness of high frequency (HFAC) sinusoidal waveforms on the pudendal nerves to produce block of the external urethral sphincter (EUS). A proximal electrode on the pudendal nerve after its exit from the sciatic notch was used to apply low frequency stimuli to evoke EUS contractions. HFAC at frequencies from 1 to 30 kHz with amplitudes from 1 to 10 V were applied through a conforming tripolar nerve cuff electrode implanted distally. Sphincter responses were recorded with a catheter mounted micro-transducer. A fast onset and reversible motor block was obtained over this range of frequencies. The HFAC block showed three phases: a high onset response, often a period of repetitive firing and usually a steady state of complete or partial block. A complete EUS block was obtained in all animals. The block thresholds showed a linear relationship with frequency. HFAC pudendal nerve stimulation effectively produced a quickly reversible block of evoked urethral sphincter contractions. The HFAC pudendal block could be a valuable tool in the rehabilitation of bladder-sphincter dyssynergia.

Bladder and urethral pressures evoked by microstimulation of the sacral spinal cord in cats.

Experiments were conducted to measure the bladder and urethral pressures evoked by intraspinal microstimulation of the sacral segments (S1-S2) in neurologically intact, chloralose anesthetized adult male cats. The bladder pressure was measured with a superpubic catheter and the urethral pressure was measured simultaneously at the level of the urethral sphincter and at the level of the penis using a two-element micromanometer. Intraspinal stimuli (typically 1 s, 20 Hz, 100 microA, 100 microseconds) were applied with activated iridium microwire electrodes in ipsilateral segments and intersegmental boundaries with a 250 micrometer mediolateral resolution and a 200 micrometer dorsoventral resolution. Increases in bladder pressures were generated by microstimulation in the intermediolateral region, in the lateral and ventrolateral ventral horn, and around the central canal. Simultaneous increases in urethral pressure were evoked by microstimulation in the ventrolateral ventral horn, but not at the other locations. Small reductions in urethral pressure (<10 cm H(2)O) were evoked at locations in the intermediate laminae and around the central canal. The magnitude of these pressure reductions was weakly dependent on the stimulus parameters. Stimulation around the central canal produced bladder contractions with either no change or a reduction in urethral pressure and voiding of small amounts of fluid. These results demonstrate that regions are present in the spinal intact anesthetized cat where microstimulation generates selective contraction of the bladder without increases in urethral pressure and that regions are present where microstimulation generates small reductions in urethral pressure.

Design, fabrication and evaluation of a conforming circumpolar peripheral nerve cuff electrode for acute experimental use.

Nerve cuff electrodes are a principle tool of basic and applied electro-neurophysiology studies and are championed for their ability to achieve good nerve recruitment with low thresholds. We describe the design and method of fabrication for a novel circumpolar peripheral nerve electrode for acute experimental use. This cylindrical cuff-style electrode provides approximately 270° of radial electrode contact with a nerve for each of an arbitrary number of contacts, has a profile that allows for simple placement and removal in an acute nerve preparation, and is designed for adjustment of the cylindrical diameter to ensure a close fit on the nerve. For each electrode, the electrical contacts were cut from 25 μm platinum foil as an array so as to maintain their positions relative to each other within the cuff. Lead wires were welded to each intended contact. The structure was then molded in silicone elastomer, after which the individual contacts were electrically isolated. The final electrode was curved into a cylindrical shape with an inner diameter corresponding to that of the intended target nerve. The positions of these contacts were well maintained during the molding and shaping process and failure rates during fabrication due to contact displacements were very low. Established electrochemical measurements were made on one electrode to confirm expected behavior for a platinum electrode and to measure the electrode impedance to applied voltages at different frequencies. These electrodes have been successfully used for nerve stimulation, recording, and conduction block in a number of different acute animal experiments by several investigators.

FUNCTIONAL ANATOMY OF THE MALE FELINE URETHRA: MORPHOLOGICAL AND PHYSIOLOGICAL CORRELATIONS

Anatomical and histological methods were combined with measurements of the urethral pressure profile (UPP) to investigate the functional aspects of the urethra in male cats. A silicone rubber catheter with two microdiaphragm pressure transducers was used to measure the UPP. Gross anatomy and ultrastructure of the urethra at each segment were examined and correlated with the pressure profile data. The preprostatic urethra was composed of three layers of smooth muscle, while distal to the prostate striated muscle became predominant. Increased baseline pressure and rapid fluctuations in pressure in the postprostatic urethra and bulbourethra resulted from the function of periurethral striated musculature. The UPP was affected by the bladder pressure, repetition of the measurement, the sensor orientation in the urethra, and the type of measurement catheter. Well controlled high fidelity measurements enabled a clear correlation to be established between the features of the UPP and the anatomy of the urethra and surrounding musculature. Additionally, observations on the ultrastructural and microscopic anatomy of the urethra extend a previous description of the pelvic urethra.

Variable Patterned Pudendal Nerve Stimuli Improves Reflex Bladder Activation

We evaluated variable patterns of pudendal nerve (PN) stimuli for reflex bladder excitation. Reflex activation of the bladder has been demonstrated previously with 20-33 Hz continuous stimulation of PN afferents. Neuronal circuits accessed by afferent mediated pathways may respond better to physiological patterned stimuli than continuous stimulation. Unilateral PN nerve cuffs were placed in neurologically intact male cats. PN stimulation (0.5-100 Hz) was performed under isovolumetric conditions at bladder volumes up to the occurrence of distension evoked reflex contractions. Stimulus evoked reflex bladder contractions were elicited in eight cats. Across all experiments, bursting of 2-10 pulses at 100-200 Hz repeated at continuous stimulation frequencies evoked significantly larger bladder responses than continuous (single pulse) stimulation (52.0 plusmn 44.5%). Bladder excitation was also effective at 1 Hz continuous stimuli, which is lower than typically reported. Variable patterned pulse bursting resulted in greater evoked reflex bladder pressures and increased the potential stimulation parameter space for effective bladder excitation. Improved bladder excitation should increase the efficacy of neuroprostheses for bladder control.

Intraurethral stimulation for reflex bladder activation depends on stimulation pattern and location

Reflex bladder excitation has been demonstrated by stimulation of the pudendal nerve and several of its distal branches. However, excitation parameters have not been consistent and the relationship to anatomical locations within the urethra has not been fully investigated. An improved understanding of the lower urinary tract neurophysiology will improve human studies and neuroprosthetic device development.

High frequency sacral root nerve block allows bladder voiding.

Dyssynergic reflexive external urethral sphincter (EUS) activity following spinal cord injury can prevent bladder voiding, resulting in significant medical complications. Irreversible sphincterotomies or neurotomies can prevent EUS activation and allow bladder voiding, but may cause incontinence or loss of sacral reflexes. We investigated whether kilohertz frequency (KF) electrical conduction block of the sacral roots could prevent EUS activation and allow bladder voiding.

Functional conditions of micturition induced by selective sacral anterior root stimulation: experimental results in a canine animal model

Abstract Electrical stimulation of the sacral anterior roots using conventional rectangular current pulses results in a simultaneous contraction of the urinary bladder and the striated urethral sphincter. Using a tripolar nerve cuff electrode with quasitrapezoidal current pulses and appropriate stimulation parameters, hyperpolarization of the nerve-fiber cell membrane under the anode of the stimulating electrode can reversibly arrest action potential propagation in large myelinated nerve fibers, innervating the striated urethral sphincter, while leaving action potential propagation unaffected in small non-myelinated nerve fibers innervating the urinary bladder smooth muscle (anodal arrest). Using this technique in 19 female mongrel dogs, we studied the effect of bladder filling, level of anesthesia, and sacral deafferentation on bladder pressure, urethral pressure, and urinary flow. Effective micturition could be induced only after complete dorsal rhizotomy, abolishing reflex contraction of the striated urethral sphincter, when blocking quasitrapezoidal current pulses were used for stimulation. Stimulation with rectangular current pulses directly induced a rise in distal urethral pressure, preventing micturition during stimulation.

Extraction Force and Tissue Change During Removal of a Tined Intramuscular Electrode from Rat Gastrocnemius

Many electrical stimulation protocols employ intramuscular electrodes for the activation of targeted muscles. Electrode displacement from the initial implant site can result in degradation of optimal stimulus parameters. Electrodes with tined tips were developed to reduce electrode migration. In the study reported here, intramuscular electrodes with polypropylene tines at the tip were implanted aseptically in the gastrocnemii of adult rats. Test electrodes were explanted immediately following implant in one group and after periods of 1, 3, 7, 14 and 28 days in others. Force as a function of displacement was recorded during removal of the electrodes. Analysis of the results showed that the electrodes were most vulnerable to movement during the first five days. Between 5 and 7 days after implantation there was significant increase in the force required to dislodge the electrode tip. Histology of muscles from which electrodes had been explanted did not show any increase in the area showing tissue changes as compared to control muscles in which the electrode remained in situ. These results indicated that electrode removal caused disruption of encapsulation tissues, with the surrounding muscle mainly unaffected by the explant process.

Direct current contamination of kilohertz frequency alternating current waveforms

Kilohertz frequency alternating current (KHFAC) waveforms are being evaluated in a variety of physiological settings because of their potential to modulate neural activity uniquely when compared to frequencies in the sub-kilohertz range. However, the use of waveforms in this frequency range presents some unique challenges regarding the generator output. In this study we explored the possibility of undesirable contamination of the KHFAC waveforms by direct current (DC). We evaluated current- and voltage-controlled KHFAC waveform generators in configurations that included a capacitive coupling between generator and electrode, a resistive coupling and combinations of capacitive with inductive coupling. Our results demonstrate that both voltage- and current-controlled signal generators can unintentionally add DC-contamination to a KHFAC signal, and that capacitive coupling is not always sufficient to eliminate this contamination. We furthermore demonstrated that high value inductors, placed in parallel with the electrode, can be effective in eliminating DC-contamination irrespective of the type of stimulator, reducing the DC contamination to less than 1 μA. This study highlights the importance of carefully designing the electronic setup used in KHFAC studies and suggests specific testing that should be performed and reported in all studies that assess the neural response to KHFAC waveforms.