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DIRECT BLADDER STIMULATION IN AN ANIMAL MODEL: EVALUATION OF A NEW SUTURE ELECTRODE

James S. Walter, John S. Wheeler, Robert B. Dunn, Richard Osgood, Robert D. Wurster Rehabilitation Research and Development Center Hines VA Hospital, Hines IL, USA; Departments of Urology, Physiology, Loyola Stritch School of Medicine, Maywood, IL, USA

ABSTRACT

To evaluate optimum methods of direct bladder stimulation, five male cats were instrumented during anesthesia. Multistranded, 316 LVM, stainless-steel, wire "suture" electrodes were implanted on the bladder wall serosa above the trigone area. Additional instrumentation included catheters for pressure recording and electrodes for pelvic floor EMG recording. Studies were conducted in tethered animals following recovery. A second surgery for spinal cord injury (T-1 level complete lesion)was then conducted followed by additional studies. Direct bladder stimulation induced active contractions and voiding both before and after spinal cord injury. Optimum stimulation parameters were similar before and after SCI and consisted of 40 pps, 300 µs to 1 ms, applied for 3 to 4 sec at 10 to 40 mA. The suture electrode did not corrode, erode into the bladder or become dislodged and appears suitable for chronic implantation.

INTRODUCTION

Direct bladder stimulation has been studied in both animals and humans with mixed results. Early clinical studies cited problems including high urethral resistance related to co-activation of striated sphincter mechanisms, poor bladder emptying, the need for high stimulating currents, and activation of lower limb muscles, pain and electrode erosion into the bladder [1]. More recently, Magasi et al., using an improved electrode obtained bladder emptying with stimulation in 29 of 32 patients without significant side effects [2]. The most effective location of the electrodes was adjacent to the ureters where the neurovascular bundle innervates the bladder. Direct bladder stimulation, however, remains controversial. High urethral resistance with direct bladder stimulation remains a major concern, and concerns with Magasi's work include the large number of electrodes and sutures on the bladder wall, and the lack of long-term results.

We have investigated electrodes for direct bladder stimulation [3]. Current studies involve a suture type electrode that might have the following advantages: (1) an extended length that could be placed across the entire neurovascular bundle that innervates the bladder, (2) implantation in the outer serosal layer that would not erode into the bladder and, (3) a simple electrode requiring little additional implantation procedures such as suturing and which might be implanted through a laparoscope. Studies were conducted in male cats both before and after SCI. Urodynamic responses to stimulation, electrode characteristics, and aspects of this animal model are described.

METHODS

Five male cats (weight 2 to 4 kg) were anesthetized and instrumented with electrodes and pressure recording tubes for subsequent studies using tethered animals. The bladder was surgically exposed via a midline incision, and suture electrodes were implanted on the bladder wall. The suture electrode cable was 50-stranded, 1 mil stainless steel wire (316LVM Cooner Wire Inc., Chatworth, CA) coated with teflon, and the electrode consisted of 7 cm of uninsulated wire. A 21G curved needle was attached to the end for suturing to the bladder wall. Four electrodes were sutured to the base of the bladder. Suturing was started above the ureters and extended downward at an angle toward the bladder neck. The suturing needle was cut off after implanting the electrode. Additional instrumentation consisted of electromyography (EMG) recording hook electrodes adjacent to the urethra. Two small diameter Silastic catheters were also sutured into the dome of the bladder for bladder filling and pressure recording. Abdominal pressure was also recorded. Electrode leads and catheters were tunneled, exteriorized and placed in an animal jacket. Animals were given Oxybutynin following recovery (1.5 mg BID) to increase bladder capacity.

METHODS

Five male cats (weight 2 to 4 kg) were anesthetized and instrumented with electrodes and pressure recording tubes for subsequent studies using tethered animals. The bladder was surgically exposed via a midline incision, and suture electrodes were implanted on the bladder wall. The suture electrode cable was 50-stranded, 1 mil stainless steel wire (316LVM Cooner Wire Inc., Chatworth, CA) coated with teflon, and the electrode consisted of 7 cm of uninsulated wire. A 21G curved needle was attached to the end for suturing to the bladder wall. Four electrodes were sutured to the base of the bladder. Suturing was started above the ureters and extended downward at an angle toward the bladder neck. The suturing needle was cut off after implanting the electrode.

A second survival surgery was conducted for spinalization 4 to 5 weeks after the animal instrumentation. The animals were reanesthetized and the T-1 spinal cord was crushed [3]. The animals were healthy for the 8 to 10 weeks following spinal injury.

Urodynamic studies were conducted with the animals tethered in a urodynamic recording cage both before and after SCI. Pressures, EMG and volume voided were recorded on a strip chart recorder. Cystometry was performed at 5 ml/min, until strong spontaneous bladder contractions occurred producing micturition.

Both bipolar and monopolar stimulation was evaluated in all five animals. For bipolar stimulation, both negative and positive electrodes were on the bladder wall, whereas, for monopolar stimulation the negative electrode was on the bladder wall and the positive electrode was the grounding electrode along the back. Capacitor coupled stimulation was conducted for balanced charge injection pulses with two stimulators (S48, Grass, Quincy, MA). Stimulating parameters evaluated in this study included the period, frequency, current and pulse duration. Stimulation studies were conducted with an initial bladder volume one-half to two-thirds of cystometric capacity.

Additional studies included electrode corrosion and postmortem evaluations. Two bladder wall electrodes were pulsed at the end of the study in a bipolar configuration for 115 hours using 40 pps with 25 mA and 1 ms pulse duration. Following euthanasia, pulsed electrodes and non-implanted electrodes were viewed with light microscopy and with scanning electron microscopy (EIC Laboratories, Norwood MA). Postmortem bladder wall thickness was evaluated after fixation with the installation of 20 ml formalin (HT50 Sigma, St. Louis, MO). Histological sections at the electrode site were stained with H&E.

RESULTS

Five male cats were instrumented before SCI, and urodynamic studies were conducted two to four weeks after surgery when oxybutynine administration had been stopped and bladder capacity had increased. Filling volumes for micturition ranged from 10 to 27 ml. Peak detrusor pressures during voiding were 32 to 75 cm H20, and the peak urine flow rates were 0.6 to 2.2 ml/sec. After SCI, an initial cystometry conducted in the second to third week after injury showed numerous small bladder contractions with little voiding. A second cystometry was condicted after five weeks. Stronger bladder contractions occurred, but the bladder contractions were short in duration with little voiding.

Direct bladder stimulation resulted in prolonged bladder contraction and voiding both before and after SCI. Before SCI, peak detrusor responses to stimulation ranged from 22 to 74 cm H20. The initial filling volume for these stimulation studies ranged from 5 to 15 ml. The maximum voiding rates were 0.5 to 1.5 ml/sec with a total volume voided with one stimulation period ranging from 5 to 15 ml and with minimal residual volume. The stimulating parameters were 40 pps, 1ms pulse duration, 3 sec train with a current ranging from 7.5 to 40 mA. Stimulation that induced strong bladder contractions in three of the five animals also caused discomfort. However, effective voiding was obtained at lower currents without noticeable discomfort to the animals.

After SCI, three of the cats voided with stimulation in the first two weeks, and two of the cats did not respond to stimulation with voiding until the the third week. Maximal responses and stimulation parameters were similar to before SCI, again the current varied from 7.5 to 40 mA. Filling volumes ranged from 6 to 40 ml. Peak detrusor responses were 22 to 74 cm H20. The maximum voiding rates in response to stimulation 5 to 8 weeks after SCI ranged from 0.1 to 1.8 ml/sec. After 4 to 20 repeated stimulations, three animals completely emptied their bladders, but two animals retained a residual of 6 and 25 ml. These poorer voiding responses at smaller filling volumes may have been due to the shorter duration bladder contractions also seen at these smaller initial volumes. There was no increase in the EMG recorded from the pelvic floor for the five cats immediately following stimulation either before or after SCI. Detrusor pressures were as high as 60 cm H20 immediately following stimulation without increased urethral resistance indicated by the EMG signal.

Effective direct bladder stimulation techniques were determined. The negative polarity applied to the anterior bladder wall electrodes and the positive polarity to the posterior electrodes was superior in 3 of 5 cats both before and after SCI. This was indicated by higher peak detrusor pressures at lower currents. Stimulation using all four electrodes resulted in higher peak detrusor pressures than any combination of only two electrodes. Also, monopolar electrodes with negative electrodes on the bladder wall and positive electrodes along the back resulted in pain before SCI and increased abdominal skeletal muscle movement after SCI. Subsequent evaluation of stimulating parameters were done using the observed optimum bipolar electrode arrangement with all of the electrodes on the bladder wall. Fluoroscopic observations of the urethra during spontaneous and stimulation induced voiding was obtained in four of the five animals. During a maximal stimulation at 40 pps for five seconds the entire urethra including the membran-ous section was seen to open. However, the penile urethra was narrow restricting urine flow.

Fluoroscopic observations urethral activity during spontaneous bladder contractions appeared the same as stimulation induced voiding.

Postmortem, mid-bladder-wall thickness was 3.3±1.1 mm for the five animals, and evaluation of the electrodes revealed that they lay in a thin connective sheath in the serosa over the bladder wall. Histological evaluation of electrode sites revealed mature fibrous connective tissue around the electrode in three cats. Smooth muscle submu-cosal and urothelium under the electrode appeared the same as areas lateral to the electrode site. However, the urothelium and submucosal areas were thickened in all three animals showing inflammatory responses. All of eight electrodes evaluated were shiny based on light microscopy without signs of corrosion after the approximately 14 weeks of implantation and studies described here. In addition, two electrodes were continuously pulsed during the last 4.5 days (115 hours) before sacrificing the animals. Upon harvesting these electrodes, light microscopy observations revealed a shiny surface without loss of metal. However, based on scanning electron microscopy the negative electrode had rare micro pits with little or no evidence of corrosion, whereas the positive electrodes had a few micro pits which were increased in localized areas.

DISCUSSION

The suture electrode appears to be a good design for direct bladder stimulation because the electrodes lay close to the bladder neurovascular bundles yet did not have problems such as erosion, migration, or excessive connective tissue formation limiting bladder filling. Implanting the electrodes with flexing helped to allow for adjustment to bladder filling. This implantation procedure is simpler than previously reported for direct bladder wall electrodes [1,2]. Since all of our electrodes were observed to lie in the outer serosa lining, erosion was not a problem in this animal model. An additional advantage of the suture electrode is that it extends over a long length of the bladder wall. This might help to activate the ramified pelvic nerves that innervate the bladder and require fewer electrodes on the bladder wall.

Current results are similar to our previous report using the "woven eye" electrode before SCI in a cat model [3]. For example, we confirm that bipolar stimulation with both electrodes on the bladder wall is more effective than monopolar stimulation with a positive distant electrode under the skin because with monopolar stimulation, abdominal contraction and pain was seen before SCI and muscle contraction associated with current spread to the distant electrode after SCI.

Good voiding responses to direct bladder stimulation were seen in this study. We conclude that stimulation before and after SCI did not increase urethral resistance based on the unincreased pelvic floor EMG immediately following the 3 to 4 sec stimulation period and fluoroscopic observa-tions showing an open membranous urethra.

In conclusion, the suture electrode appears to be effective in activating the bladder in an SCI animal model. However, any clinical applications of the suture type electrode should take into consideration the limitation of this animal model. For example, clinical applications of direct bladder stimulation undoubtedly will require procedures to reduce or eliminate high urethral resistance.

REFERENCES:

1. Tallala, A., Bloom, J.W., and Quang, N.: FES for bladder: direct or indirect means? Pace, 10:240-245, 1987

. 2. Magasi, P., and Simon, Z.S.: Electrical stimulation of the bladder and gravidity. Urol. Int., 41:241-245, 1986.

3. Walter, J.S., Wheeler, J.S., Cogan, S. F., Plishka, M., Riedy, L. W., and Wurster, R.D. Evaluation of direct bladder stimulation with stainless steel woven eye electrodes. J. Urol., 150:1990-1996, 1993.

ACKNOWLEDGEMENT:

Supported by the the NIH, National Center for Medical Rehabilitation Research (R01-HD30529-01) James S. Walter, Ph.D. Hines VA Hospital; Rehabilitation R&D Center (151L); P.O. Box 20 Hines, IL 60141 Phone: (708) 343-7200, Ext. 5805