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ELLIS ET AL.: ELECTRICAL STIMULATION OF BLADDER 857 EXPERIMENTAL ELECTRICAL STIMULATION OF THE BLADDER BY FRANK ELLIS AND JOAN PARKER AND MICHAEL HILLS DEPARTMENT OF SURGERY, GUY’S HOSPITAL LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE THE development of cardiac pacemaking with small indwelling sealed transistorized stimulators which give a reliable performance over long periods leads to the possibility that disordered organs other than the heart might be made to function satisfactorily. This paper reports the results of electrical stimulation of the bladder in dogs in an attempt to make it empty. The report concerns the normally innervated bladder. The bladder seemed an appropriate organ for investigation because the application of an artificial stimulus to produce contraction is the logical method of treatment of those cases of urinary retention which are due to bladder weakness rather than to increased resistance in the outflow tract. Although most cases of urinary retention are due to the latter cause and are appropriately treated by reducing the urethral resistance, it is also the practice to apply this method to cases of retention due to bladder paralysis. To ensure drainage in the acute cord bladder it is necessary to reduce the resistance of the outflow tract to its lowest possible level by catheterization : trans- urethral resection of the bladder neck and external urethral sphincterotomy for chronic paralytic reten- tion are based on the same principle. In these conditions where detrusor action is impaired it may be necessary to reduce the resistance of the outflow tract to such an extent that the patient is incontinent on straining or standing. Neither this nor the well- known evils of catheterization have led to any change in the principles of treatment adopted, though the techniques of reboring have improved considerably. Fig. I shows that there is an abundance of methods available for treating retention by reducing the resistance of the outflow tract, while there are only two (manual compression and reflex stimulation) which increase intravesical pressure. Where urinary retention is due to weakness of detrusor action, direct stimulation of the muscle in an endeavour to make it contract is logical. Such a measure attempts to correct the primary defect and avoids the diffi- culties associated with reducing the resistance of the outflow tract. Certain physiological properties of bladder muscle lend credence to the idea that it might be possible to achieve, by electrical stimulation, a degree of con- traction sufficient to produce emptying. The pro- perties of electrical excitability of bladder muscle were described by Stewart in 1900, and from his references to earlier work it appears that the basic phenomena were known for many years before. More recently (Ingersoll, Jones, and Hegre, 1955) it has been shown that, even after denervation, an electric current will produce contractions similar to those in the normal bladder. Dissection of the bladder musculature shows that the concept of the detrusor having three layers and being largely separate from the internal sphincter is incorrect. The bladder musculature is, in the main, diffusely and homogeneously arranged (McCrea, 1926). Many of the detrusor muscle bands are long and extend from the fundus down through the bladder neck to the posterior urethra. At this point DIRECT STIMULATION METHODS OF INCREASING INTRAYESICAL PRESSLIRE Manual Compression Reflex Stimulation METHODS OF REDUCING OUTFLOW TRACT RESISTANCE CatheterisatLon Suprapublc Cystostomy Prostatectomv OF REDUCING TRACT RESISTANCE isation 31c Cystostomy P rb st it e c to m v Bladder Neek.Resection Sphincterotamy Pudendal Neureetomy Urinary Diversion FIG. r.-Methods of treating urinary retention. the convergence of these muscle bands produces thickening of the bladder wall. This has led to the mistaken concept of the presence of an internal sphincter at the bladder neck. The muscle bands are not circular at this point and could not act as a sphincter. During recent years ideas on the mechanism of micturition have changed fundamentally. In sum- mary, evidence has been adduced which shows that :- I. The smooth muscle of the bladder and posterior urethra form a motor unit which, acting alone, will void urine without the aid of voluntary muscles. 2. The complete act of micturition can be achieved by contraction of the detrusor without active relaxa- tion of the smooth muscle around the bladder neck. Indeed, it has been shown that the widening of the bladder neck which occurs during micturition is not due to relaxation. In a series of publications on the mechanism of micturition, Lapides and his colleagues (1955, 1957, 1958, and 1960) showed that in normal subjects micturition could be initiated, controlled, and stopped satisfactorily after the pelvic floor muscles had been paralysed by bilateral pudendal nerve-block. Even complete curarization of all voluntary muscles had little effect on micturition other than some impediment to cutting off the stream suddenly. In neither case does incontinence result. The voluntary muscles of the abdominal wall and pelvic floor may aid in the finer control of micturition but they are not necessary for its performance.

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Page 1: Experimental electrical stimulation of the bladder

ELLIS E T AL.: ELECTRICAL STIMULATION OF BLADDER 857

EXPERIMENTAL ELECTRICAL STIMULATION OF THE BLADDER

BY FRANK ELLIS AND JOAN PARKER

AND MICHAEL HILLS

DEPARTMENT OF SURGERY, GUY’S HOSPITAL

LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE

THE development of cardiac pacemaking with small indwelling sealed transistorized stimulators which give a reliable performance over long periods leads to the possibility that disordered organs other than the heart might be made to function satisfactorily. This paper reports the results of electrical stimulation of the bladder in dogs in an attempt to make it empty. The report concerns the normally innervated bladder.

The bladder seemed an appropriate organ for investigation because the application of an artificial stimulus to produce contraction is the logical method of treatment of those cases of urinary retention which are due to bladder weakness rather than to increased resistance in the outflow tract. Although most cases of urinary retention are due to the latter cause and are appropriately treated by reducing the urethral resistance, it is also the practice to apply this method to cases of retention due to bladder paralysis. T o ensure drainage in the acute cord bladder it is necessary to reduce the resistance of the outflow tract to its lowest possible level by catheterization : trans- urethral resection of the bladder neck and external urethral sphincterotomy for chronic paralytic reten- tion are based on the same principle. In these conditions where detrusor action is impaired it may be necessary to reduce the resistance of the outflow tract to such an extent that the patient is incontinent on straining or standing. Neither this nor the well- known evils of catheterization have led to any change in the principles of treatment adopted, though the techniques of ‘ reboring ’ have improved considerably. Fig. I shows that there is an abundance of methods available for treating retention by reducing the resistance of the outflow tract, while there are only two (manual compression and reflex stimulation) which increase intravesical pressure. Where urinary retention is due to weakness of detrusor action, direct stimulation of the muscle in an endeavour to make it contract is logical. Such a measure attempts to correct the primary defect and avoids the diffi- culties associated with reducing the resistance of the outflow tract.

Certain physiological properties of bladder muscle lend credence to the idea that it might be possible to achieve, by electrical stimulation, a degree of con- traction sufficient to produce emptying. The pro- perties of electrical excitability of bladder muscle were described by Stewart in 1900, and from his references to earlier work it appears that the basic phenomena were known for many years before. More recently (Ingersoll, Jones, and Hegre, 1955) it has been shown that, even after denervation, an electric current will produce contractions similar to those in the normal bladder.

Dissection of the bladder musculature shows that the concept of the detrusor having three layers and being largely separate from the internal sphincter is incorrect. The bladder musculature is, in the main, diffusely and homogeneously arranged (McCrea, 1926). Many of the detrusor muscle bands are long and extend from the fundus down through the bladder neck to the posterior urethra. At this point

DIRECT STIMULATION

METHODS OF INCREASING INTRAYESICAL PRESSLIRE

M a n u a l C o m p r e s s i o n R e f l e x S t i m u l a t i o n

METHODS OF REDUCING OUTFLOW TRACT RESISTANCE

C a t h e t e r i s a t L o n S u p r a p u b l c C y s t o s t o m y P r o s t a t e c t o m v

OF REDUCING TRACT RESISTANCE

i s a t i o n 31c C y s t o s t o m y

P rb s t i t e c to m v B l a d d e r N e e k . R e s e c t i o n S p h i n c t e r o t a m y P u d e n d a l N e u r e e t o m y U r i n a r y D i v e r s i o n

F I G . r.-Methods of treating urinary retention.

the convergence of these muscle bands produces thickening of the bladder wall. This has led to the mistaken concept of the presence of an internal sphincter at the bladder neck. The muscle bands are not circular at this point and could not act as a sphincter.

During recent years ideas on the mechanism of micturition have changed fundamentally. In sum- mary, evidence has been adduced which shows that :-

I. The smooth muscle of the bladder and posterior urethra form a motor unit which, acting alone, will void urine without the aid of voluntary muscles.

2. The complete act of micturition can be achieved by contraction of the detrusor without active relaxa- tion of the smooth muscle around the bladder neck. Indeed, it has been shown that the widening of the bladder neck which occurs during micturition is not due to relaxation.

In a series of publications on the mechanism of micturition, Lapides and his colleagues (1955, 1957, 1958, and 1960) showed that in normal subjects micturition could be initiated, controlled, and stopped satisfactorily after the pelvic floor muscles had been paralysed by bilateral pudendal nerve-block. Even complete curarization of all voluntary muscles had little effect on micturition other than some impediment to cutting off the stream suddenly. In neither case does incontinence result. The voluntary muscles of the abdominal wall and pelvic floor may aid in the finer control of micturition but they are not necessary for its performance.

Page 2: Experimental electrical stimulation of the bladder

858 BRIT. J. SURG., 1964, Vol. 51, No. 11, NOVEMBER

The widening of the bladder neck which occurs during micturition has been supposed by Denny Brown and Graeme-Robertson (1933) to be due to relaxation of a sphincter muscle, the innervation of which is reciprocal with the detrusor. There has thus grown the idea that a process of relaxation at the bladder neck is fundamental to the passage of urine during micturition. However, Lapides (1958) has shown that the increase in the size of the lumen

LRECENER~-(RECORDERJ I

1 : ~ ; . 2.-Exprrimental technique for recording results of electrical stimulation.

is due to shortening and widening of the bladder neck and is produced by contraction of those fibres of the detrusor which pass through this region to the posterior urethra. From this it appears that if detrusor activity spreading to the bladder neck could be induced by electrical stimulation, then the widening of this part of the outflow tract which occurs in normal micturition would follow.

Finally (assuming a normal ureterovesical mecha- nism preventing reflux) the bladder is a hollow organ with only one outlet. If the intravesical pressure could be raised and maintained above the urethral resistance, micturition would follow.

EXPERIMENTAL TECHNIQUE Thirty-six mongrel dogs of both sexes were used

for acute experiments. Under pentothal anaesthesia, 3f sufficient depth to abolish voluntary muscle activity, the bladder was exposed through a low midline incision and the effects of direct electrical stimulation were observed. Each stimulus was applied for 10 seconds. During the initial experi- ments the bladder was stimulated only ten to twenty times in each dog, but in the later experiments upwards of fifty stimuli, each producing a voiding contraction, were observed in each animal.

The apparatus is shown diagrammatically in Fig. 2.

The Stimulator.-The instrument used in the majority of the experiments was an A.E.L. Model ro4A Square Wave Stimulator with wide ranges of frequency, voltage, and duration control. The frequency and duration output were controlled by the dials on the machine, but the voltage output was measured directly across the output leads with an oscilloscope. This was necessary because measure- ments of the resistance across the leads showed that there was a marked difference between the impedance of’ the preparation and the internal circuitry of the

stimulator and that under these conditions the voltage setting on the dial was inaccurate. Observation of the wave form invariably revealed minor distortions, but the leading edge was always vertical and the duration of the peak voltage was maintained. In the later experiments separate stimulators (A.E.L. IO@, Palmer Electronic Square Wave Stimulator, and Multitone Ten Pulse Stimulator) were used for each pair of leads.

The bladder was filled with saline (maintained at 37” C. by a water jacket) through a polythene catheter introduced into the ureter. The volume used varied with each animal and was 75 per cent of the bladder capacity.

In the first series of experiments the response of the bladder was monitored by measuring intravesical pressure and in the second series by measuring directly the percentage of the contents voided through the urethra (i.e., through a normal outflow tract). Intravesical pressure was measured by a pressure- sensitive radiosonic pill introduced through a small stab incision in the fundus of the bladder. The output from this was transmitted by an aerial to a radio receiver (Solartron E.I.L., Radio Pill Receiver Model 70A), and a continuous written record of pressure was obtained by feeding the output from the receiver into a pen recorder (Cardiac Recorders Ltd.). Several pressure records thus obtained were compared with simultaneous records using a pressure transducer. They showed that the radiosonic pill provided an accurate record of intravesical pressure changes. I n the second series of experiments the percentage volume of bladder contents voided through the urethra was obtained by direct collection and measurement of the urine passed on stimulation after a known volume had been introduced into the bladder.

The Leads.-Initially two surface-contact copper electrodes were used. With these the stimulus spread to the surrounding tissues, and bladder

FIG. 3.-Three stainless-steel wire electrodes were inserted into the wall of the bladder near the ureterovesical junction. They were carried over the fundus and down the anterior wall to the bladder neck.

contraction was inadequate. Atraumatic braided pacemaker wire leads were used in all subsequent experiments and stitched into the bladder muscle in the manner shown in Fig. 3. The leads were insulated by polythene up to the point of entry into the bladder. Eventually the number of leads used was three, the central one acting as a common

Page 3: Experimental electrical stimulation of the bladder

ELLIS ET AL.: ELECTRICAL

First Second

Leads 3

Voltage 5 v. 20 C.P.S.

1.0 msec.

negative to the two outer ones which were connected to the positive output of the stimulators.

Third Fourth

- 4 30 C.P.S. 40 C.P.S.

6 V. 7 v. 1’5 msec.

RESULTS Fig. 4 shows a typical record of intravesical pressure

changes following a stimulus which caused the bladder to empty 80 per cent of its contents. The resting pressure in the filled bladder was usually from 5-10 cm. water. Stimulation produced a sharp rise in pressure to 50 cm. water and micturition began. I t continued for 3 seconds after the cessation of the stimulus and stopped when the pressure fell to 20 cm. water. Thereafter, as the bladder relaxed, the pressure fell to a point equal to or below that of its resting state. The maximum pressure developed in the bladder while voiding (i.e., the difference between peak pressure and resting pressure) and the per- centage volume of bladder contents voided showed no correlation, so that this voiding pressure could not be used as a measure of the degree of emptying of the bladder on stimulation.

Although the measurement of the percentage volume voided was the most accurate method of

the response, it was a time-consuming

RETAINING PRESSURE RECORD

50

30

10

STIMULUS 10 sec.

c 1

FIG. s.--Intravesicd pressure with the urethra occluded. Stimulus 6 V.; 20 c.P.s.; 0.5 msec. The pressure rise is more sustained and falls more slowly than in Fig. 4 because the bladder cannot empty. R.P., retaining pressure; M.P., maximum pressure.

procedure and its use meant having to extend each experiment over several hours to get sufficient read- ings. A search was made for an alternative measure of intravesical pressure, which could be obtained easily and which correlated satisfactorily with the percentage volume voided. The pressure developed in the closed bladder under stimulation proved to be a suitable measure. I t was called the retaining pressure. It was obtained by filling the bladder and stimulating it while the proximal urethra was lightly occluded with a small bulldog clip. The pressure developed (the retaining pressure) could be correlated satisfactorily with the percentage volume voided when the same stimulus was applied im- mediately afterwards and the bladder allowed to empty. Fig. 5 shows that in the retaining-pressure record the pressure rise is abrupt for the first 3 seconds; thereafter it rises more slowly, reaching its peak at the end of the stimulus. Fig. 6 shows the relationship between the maximum retaining pres- sures and the volume voided in a single dog. If this pressure failed to exceed 20 cm. of water the bladder did not empty. At 35 cm. the pressure developed

STIMULATION OF BLADDER 859

appeared to be sufficient to overcome outflow tract resistance, and thereafter the volume voided increased rapidly until, at a pressure of 50 cm., 75 per cent of the contents emptied. Above this pressure the increase in volume voided per unit increase in pressure was small. Similar relationships were obtained in other dogs, the general shape of the curve being the same,

VOIDJNG PRESSURE RECORD

Micturition 80% - O L ,STIMULUS,

10 sec. FIG. 4.--Intravesical pressure during voiding. Stimulus 6 V. ;

20 c.P.s.; 0.5 msec. The pressure rises abruptly on stimulation and falls off rapidly as emptying occurs (cp. Fig. 5 ) .

..... 0 t * ......._

I 0 10 20 30 40 50 60 70 80

Pressure cm. H20

FIG. 6.-Pressure-voiding relationship in a single dog. The intravesical pressure was first measured with urethra occluded. Thereafter the same stimulus was repeated without urethral occlusion and the volume voided was measured.

with small shifts to the right or left. The steep ascent of the midpart of the curve occasionally gave rise to difficulty in the interpretation of the bladder response, but the ease with which the retaining pressure could be recorded and the increased number of recordings which its use facilitated overcame these difficulties.

Table I.-VARIABLES IN THE STIMULUS USED IN THE FIRST SERIES OF EXPERIMENTS

For the first series of experiments the retaining- pressure record was used as a measure of the response of the bladder to stimulation (Table I ) . By varying the stimulating current it was determined that at low levels

Page 4: Experimental electrical stimulation of the bladder

860 BRIT. J. SURG., 1964, Vol. 51, No. 11, NOVEMBER

of frequency (5 c.P.s.), duration(o.1 msec.), andvoltage The method used to determine this weakest ( I V.) the bladder showed little response to square- current follows. In the first series of experiments wave stimulation. Increasing the number of pairs of the range of interest of each factor involved in the leads stitched into the bladder appeared to increase current was divided into roughly equal steps. the response, but this enhancement was not seen if Starting with the first two levels of each factor, more than three pairs of leads were used. Increasing each of the 24= 16 combinations was applied in the frequency, duration, or voltage independently random order to a bladder and the retaining pressure

COMBINATION OF

RETAINING

LEVELS I (1)

PRESSURE 12 (cm. water)

Table II.-RESULTS OF EXPERIMENT I

The results are set out in the usual way for factorial experiments. The presence of a symbol in the first row indicates that that factor is at its high level and the absence that it is at its low level. E.g., bc stands for the combination 2 leads, 20 c.P.s., 5 V., and 0.3 msec. (The main effects and interactions shown by these results arc given in Table V.)

a

34 46 67 1 28 1 52 1 76 1 67 I 20 1 37 1 65 1 70 1 51 61 1 75 1 77

b ab 1 c I ac I bc I abc 1 d 1 ad 1 bd I abd 1 cd acd bcd abcd --- ------- __

-~ ~ _____

-~ HIGH LEVEL

Low LEVEL I 2 1 10 c.p.s. 1 4 V. 1 0.3 msec.

Table III.-RESULTS OF EXPERIMENT 2

in Table V. The combinations of symbols have the same meaning as in Table I . The main effects and interactions are given

COMBINATION OF LEVELS I ( I ) I a I b I ab I c I ac I bc I abc I d I ad I bd I abd I cd I acd I bcd I abcd

c =Voltage d 5 Duration

HIGH LEVEL 13 30 C.P.S. 1 -<r---- 1.0 msec.

Law LEVEL 1 2 1 20 C.P.S. I 4 V. -1- 0.3 msec

Table IV.-RESULTS OF EXPERIMENT 3

in Table V. The combinations of symbols have the same meaning as in Table I. The main effects and interactions are given

COMBINATION OF LEVELS I ( I ) I a I b I ab I c I ac I bc I abc I d 1 ad I bd I abd 1 cd I acd I bcd I abcd

RETAINING PRESSURE 1 48 I 46 I 46 I 47 I 51 1 53 1 55 1 50 I 5 0 1 5 1 1 57 I 54 I 65 1 61 I 65 I 65

HIGH LEVEL 30 C.P.S. 1 6 V. 1 I 5 msec.

I a=Leads 1 b-Frequency c=Voltage d -Duration ,-I--,- ~

l 2 l Z 0 Law LEVEL

produced brisk bladder emptying, but if these were increased simultaneously beyond certain limits (frequency IOO c.P.s., duration 2-3 msec., voltage 10 V.) visible damage to the bladder occurred at the site of contact of the tissues with the electrodes. In view of this it seemed possible that smaller degrees of damage, macroscopically undetectable, were occurring with lesser currents and that to reduce this to a minimum the weakest current able to produce bladder emptying in the majority of dogs should be determined.

C.P.S. 1 5 v. 1 1.0 msec.

measured. The results of this z4 factorial experiment are given in Table ZZ. The level of each factor is usually referred to as ‘high’ and ‘low’. In the row of symbols referring to the combinations of levels the presence of a letter indicates that the corresponding factor is at its high level and its absence that the factor is at its low level. The symbol (I) means that all factors are at their low levels.

The main effect of any factor is defined as the increase in response due to raising the level of that factor averaged over the high and low levels of all the

Page 5: Experimental electrical stimulation of the bladder

ELLIS E T AL.: ELECTRICAL STIMULATION OF BLADDER

Main Effects Leads Frequency Voltage Duration

86 I

EXPERIMENT EXPERIMENT EXPERIMENT T I - ! -;:: 12'1 31.6 16.4 24'9 10'0 30.6 10'1

other factors. The interaction between two factors (say, a and b) is defined as one-half of

increase in response due to raising a when b is high -increase in response due to raising a when b is low.

Both of these terms are averaged over all levels of all factors other than a and b. (For further details about factorial experiments see Cox, 1958.)

Table V.-THE MAIN EFFECTS AND INTERACTIONS OF THE FOUR FACTORS OF THE STIMULUS

A high value indicates an important effect. Thus the most important effect in Experiment I was from increasing the frequency (31-6); in Experiment z the voltage and duration (24.9 and 30.6). The main effects in Experiment 3 were much lower than in the first two experiments. The interactions were all unimportant compared with the

main effects.

PROGRESSIVE STIMULI

C.P.S. Voltage Duration

(2 prs. leads)

A

10 20 20 20 20 20 4 4 4 5 5 6

0.3 0.3 1.0 1.0 1.5 1.5

Interactions Leads x Frequency Leads x Voltage Leads x Duration - 3'6 -4.6 -1.4

Number of dogs voiding 80 per cent or more of bladder contents

Frequency x Voltage -4.6 3'4 0.4 0.6 Frequency x Duration

Voltage x Duration 1 -;:: 1 -;:: I 1.6

0/6 0,6 4 6 416 4 /6 5 6

The estimated main effects and interactions of the four factors at these levels are given in Table V (Experiment I). It will be noted that frequency had by far the largest main effect (and therefore at these levels it was the most advantageous factor to in- crease). The experiment was repeated using a

Table VZ.-THE PERCENTAGE OF BLADDER CONTENTS VOIDED WITH STIMULI OF INCREASING STRENGTH

All stimuli applied for 10 sec.

.. 34 10 is 46 90 95 89 I 43 65 I00 100 96 97 -_ - _ _ ~ - - 36

Mean per cent volume voided 1 4 1 51 76 86 83 87

I

different bladder and, although the main effects changed in size, their order of importance remained unaltered.

A second 24 factorial experiment was carried out using a new bladder and using the first two levels of all factors except frequency for which the levels

were increased to be the second and third. The results of this experiment are given in Table III . The estimated main effects and interactions are given in Table V (Experiment 2) . I t will be noted

I/ + Duration (d) (m. sec.)

F

Frequency Voltage Duration

1.0 20 1. 5 20 1. 5

FIG. 7.-The sequence of stimuli represents the results of the three 2 4 factorial experiments. In each case the step taken is the one producing the greatest increase in the response of the bladder.

that both voltage and duration had high but not very different main effects and the interactions between these two factors were low. This indicated that in the next 24 factorial experiment both voltage and duration should also be increased to their second and third levels, leaving only the number of leads at its first two levels. The results of this experiment are given in Tables IV and V (Experiment 3) and again voltage and duration have high main effects with a low interaction, indicating that it was advantageous to raise these factors still further. In each of these three experiments the main effects were large compared with the interactions, and in analysis of variance in the first two experiments, in which the interactions were taken to be due to random error, all main effects were highly significant. In the third experiment the main effects of voltage and duration were still highly significant but were considerably less than the corresponding main effects in the second experiment.

The result of these three experiments was to produce a sequence of stimuli starting at

and ending at

(the intermediate stimuli being shown in Fig. 7). Each stimulus in the sequence was reached from

the preceding one by a single step of that factor which gave the greatest increase in response. Where two factors were raised in an experiment they were arbitrarily separated. It was known (Fig. 6) that the intravesical pressure attained by stimulus F would cause the majority of bladders to empty and the first series of experiments was stopped at this stage.

In the second series of experiments the percentage of bladder contents voided was used as the response. Measurement of the volume voided in 6 dogs using the same stimuli (A-F) as in the first series confirmed that these stimuli produced progressively increasing

2 leads, 10 c.P.s., 4 V., 0.3 msec. (Stimulus A)

2 leads, 20 c.P.s., 6 V., 1.5 msec. (Stimulus F)

Page 6: Experimental electrical stimulation of the bladder

862 BRIT. J . SURG., 1964, Vol. 51, No. 11, NOVEMBER

contractions, and with the strongest stimulus (F) j out of 6 dogs emptied 80 per cent or more of their bladder contents. Table VZ shows the details of the responses in each of these dogs. With the weakest stimuli A and B the mean volume voided was 41 per cent

and

and 5 1 per cent respectively. With stimuli C

reduce urethral resistance. The intravesical pressures obtained by electrical stimulation in the dog are higher than the maximum pressure reached in micturition in men. Murphy and Schoenberg (1960) have shown that the latter is 21-35 cm. H,O. Intravesical pressures of twice this value can

A B .. - FIG. 8.-Cystogram showing, A, the distended bladder before emptying. After stimulation for KO seconds,

B, the bladder was virtually empty.

D 2 dogs achieved complete voiding, the mean response being 76 per cent and 86 per cent. Stimuli E and F gave similar results to D, confirming that, as in the first series of experiments, increasing the stimulus at this level had only a small effect.

The degree of emptying of the bladder produced by stimuli D, E, and F was of the same order. The fact that the increase in response gained by increasing the strength of the current from D to F was not critical suggests that the optimum stimulus lies in this region. Stimulus F (2 leads, 20 c.P.s., 6 V., 1.5 msec.) produced 80 per cent micturition in 5 out of 6 dogs. Fig. 8 shows a cystogram of one of the dogs before, A, and after, By stimulation. The bladder has expelled virtually all its contents.

Bladder Damage.-In 8 dogs the site of the bladder wall which had been traversed by the leads was examined microscopically after stimuli of sufficient strength to produce voiding had been applied over fifty times in approximately z hours. No evidence of tissue damage was seen.

DISCUSSION The technique employed shows that a low-energy

current achieves satisfactory emptying of the fully innervated bladder against a normal urethral resis- tance. No microscopic evidence of damage to the tissues occurred in the experiments, in which the bladder was stimulated over fifty times in 2-3 hours. If such techniques can be successfully extended to the denervated bladder the method may have an application in the treatment of permanent paralytic urinary retention, thereby avoiding the sepsis occurring with indwelling catheters and the possible incontinence accompanying procedures designed to

achieved regularly by electrical stimulation in dog.

be

the

Eradley and his colleagues (1962, 1963) have reported favourable results from electrical stimulation of the bladder in the dog both before and after denervation. In both acute and long-term experi- ments they were able to achieve satisfactory emptying. Using biphasic square-wave stimulation with disk electrodes applied to the external surface of the bladder, intravesical pressures of up to 68 cm. water were obtained. Tissue damage was minimal. The most satisfactory parameters were found to be 20-25 pulses per second? S-ISV., and 1-8 msec. duration. The total period of application of the stimulus was 1-3 minutes. These values are higher than the optimum stimulus as determined by the present experiments and with braided wire leads would lead to local tissue damage. Such damage may cause fibrosis around the leads and a rise in the threshold stimulus of the bladder muscle. These changes necessitate the use of even stronger stimuli, resulting in progressive damage. The optimum wave form for stimulation has yet to be determined. It is possible that a bipolar wave may be the most satis- factory.

Bradley, Wittmers, Chou, and French (1962) found no material difference in the responses of the bladder before and after denervation, either by cord section or cauda equina section. Using an indwelling stimulator and an external radio transmitter circuit to induce the flow of current, dogs have maintained satisfactory micturition for prolonged periods. The longest surviving dog has a stimulator circuit function- ing satisfactorily after 13 months, the bladder being emptied at 4-hourly intervals.

Page 7: Experimental electrical stimulation of the bladder

ELLIS ET AL.: ELECTRICAL STIMULATION OF BLADDER 863

Schamaun and Kantrowitz (1963) havealso reported on the use of a radio-linked stimulator. Two stainless- steel wire electrodes were implanted in the detrusor muscle and, with stimuli of 4 msec., 20 c.P.s., and 15-25 V., the bladders of both normal and paraplegic dogs could be constantly evacuated.

Schoenberg, Young, and Murphy (1963) have reported the use of various wave forms and elec- trodes and have gained the most satisfactory results from monophasic square-wave stimuli of frequency 25 c.P.s., voltage 18-25 V., and duration 0'5-2'0 msec. The stimulus was applied for 8-12 sec. With the exception of a higher voltage, these parameters are nearer those found to be optimal by us. They found the most satisfactory electrodes were stainless-steel needles placed in the dome of the bladder and near the ureterovesical junction.

Habib (1963)~ by direct stimulation of the motor nerves, using disk electrodes, has found (in acute and chronic experiments) that a 1-2 V., 20 C.P.S. square wave with duration of 15 msec. applied for 30-40 sec. would empty the bladder effectively.

After preliminary trials in dogs, Burghele, Ichim, and Demetresco (1959) reported that the method of electrical stimulation had been used successfully in paralytic retention in patients, but few details are given.

Bradley and others (1963) have applied their stimulating technique in 7 patients. All had neuro- genic bladders and were treated by implantation of receiver stimulator systems powered by external inductance. In 5 patients in whom disk electrodes were used, the contraction of the bladder was not sufficient to accomplish voiding, but in 2 cases where tape electrodes were employed almost complete evacuation was consistently achieved. The design of the electrodes appears to be an important factor in determining the response of the bladder. If this and the reliability of the receiving units can be improved, bladder pacemaking may be a satisfactory method of treating neurogenic retention.

SUMMARY Recently it has been shown that detrusor con-

traction alone can produce a voiding contraction of the bladder. Voluntary muscle activity is unnecessary for micturition and the existence of a sphincter at the bladder neck is in serious doubt. As the detrusor contracts, the bladder neck becomes shorter and wider, thereby reducing the resistance to the outflow of urine.

These findings together with the development of efficient indwelling electrical stimulators lead to the possibility that the bladder may be made to empty by direct electrical stimulation of the detrusor muscle. In urinary retention of neurogenic origin this method appears to be logical because its aim is to correct the primary fault in the emptying mechanism.

Direct electrical stimulation of the normally innervated bladder has been carried out in anaes- thetized dogs. At open operation braided wire electrodes were stitched into the bladder wall. Using square-wave stimulation the response of the bladder was measured in a first series of experiments by recording the intraluminal pressure with a radiosonic

capsule. A sequence of 24 factorial experiments led to a rapid assessment of the importance of four parameters in the stimulus and thereby the range of efficient stimuli was discovered with the minimum number of experiments. A second series of experi- ments was carried out with the same stimuli, and the volume of urine voided through the normal urethra after each stimulus was measured. The bladder was made to empty most of its contents with stimuli ranging from 2 leads, 20 c.P.s., 5 V., 1.0 msec. to 2 leads, 20 c.P.s., 6 V., and 1.5 msec. With the latter stimulus 5 out of 6 dogs emptied over 80 per cent of their bladder contents.

The literature shows that similar work in dogs has already demonstrated the feasibility of achieving adequate bladder contraction by electrical stimulation using radio-linked stimulators. The effects are almost the same after denervation of the bladder by division of the spinal cord. The method has been used with limited success in patients. The results obtained in the experiments described here confirm that the technique should be investigated further with a view to its use in urinary retention of neurogenic origin.

We are grateful to Professor Hedley Atkins and Professor Armitage, who kindly gave us their advice, and to the members of the staff of the Illustration Department for their help. This work was carried out with the aid of a grant from the Medical Research Council.

A paper on this subject was read by one of the authors (F.E.) at the nineteenth meeting of the Surgical Research Society in November, 1963.

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