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Mechanism of trigonal influence on ureter during bladder filling and voiding An experimental study in dogs
MECHANISM ON
OF TRIGONAL
URETER
FILLING
DURING
AND
An Experimental SUBBARAO HARRY PAUL
V. YALLA,
INFLUENCE
BLADDER
VOIDING Study in Dogs M.D.
M. BURROS,
M.D.
D. ZIMSKIND,
M.D.
From the Departments of Urology, Graduate Hospital of the University of Pennsylvania, and Thomas Jefferson University
Hospital,
Philadelphia,
Pennsylvania
ABSTRACT-The role of the trigone and the mechanisms involved in its influence on the ureteral activity during bladder filling and voiding were investigated in 5 groups of adult mongrel dogs. The study included an evaluation of the influence of nontrigonal factors. Stimulation of the trigone with electric current and induced voiding was performed and the activity in the ureters in which linear vents were created proximal to the ureterovesical junction was monitored. Trigonal electromyography supplemented the studies. The results indicated that nontrigonal intravesical factors additionally operated on the ureter. The mechanism of the trigonal influence on the ureter was twofold. It produced maximal response at the ureterotrigonal junction causing obstruction at the terminal segment of the intravesical ureter. Second, the trigonal activity propagated proximally into the adjacent ureter, which thereby exhibited a direct smooth muscle response. Electromyographic studies of the trigone revealed increased spike activity even during nonvoiding stage of passive bladder filling.
The occurrence of changes in ureteral dynamics during bladder filling and voiding has been well documented with experimental and clinical studies.1-5 Obstruction at the ureterovesical junction was believed to cause these changes, and various intravesical factors were proposed by many workers (Fig. 1). Tanagho et al? suggested that the ureter was principally governed by the trigone during bladder filling and micturition, and they considered that the vesical factors mentioned by others played a minimal ro1e.2,6,7 The anatomic and embryologic studies reveaI that the trigone and the ureter are intimately related to each other. *ssA physiological syncitium probably exists in the trigonoureteral musculature, with these two structures either being interdependent or conjointly responding to the same stimuli. We believe the trigone influences the ureter directly, by virtue of its muscular activity transmitted proximally. It is known from other
UROLOGY
/ AUGUST
1973 / VOLUME
II, NUMBER
2
studies that the trigone actively contracts during voiding phase of micturition.g-ll The changes in
INTRAMURAL COYFRESSION OF THE URETER
II
BY
MTRUSOR CONTRACEQN (HOMSY)
:AL PRESSURE
INCREASE IN WALL TENSION
INCREASE SONAL STRETCH D CONTRACTION
FIGURE 1.
and site voiding.
IN OBLIOUITY
OF THE INTRAVESICAL URETER
Current concepts of obstructive factors of operation during bladder filling and
153
ureteral activity during voiding could, therefore, result from more than one mechanism governed by the trigone. This experimental study was aimed at investigating these possibilities and precisely evaluating the extent of trigonal influence on the ureter during bladder filling and micturition. Attempts were made to find out if any nontrigonal, intravesical factors additionally operated on the ureter. This study further attempted to probe if any trigonal activity existed during passive bladder filling phase and if this activity influenced the ureter.
ELECTRICAL STIMULATION OF EXPOSED TRIGONE
Material and Methods The experimental mode1 essentially consisted of antegrade ureteral infusion with a constant rate of saline and of recording the ureteral activity during bladder distention, voiding contractions, and electrical stimulation of the trigone (Fig. 2). were categorized into 5 The experiments groups (Fig. 3). In group I, attempts were made to evaluate the role of nontrigonal intravesical factors by eliminating the trigonal influences on the ureter. An intravesical, submucous transection of the ureterotrigonal junction was performed. Interpretation of the results was made after making certain that no vesicoureteral reflux resulted following ureterotrigonal discontinuity. In group II, direct application of the electric current on the exposed trigone was made. The changes in the ureter were entirely caused by the trigonal stimulation. For a comparison, nontrigonal areas on the bladder were also stimulated. Group III experiments evaluated the mechanism of trigonal influence on the ureter during trigonal electric stimulation, bladder distention, and voiding contraction. The experiments were conducted to investigate if any direct propagation THE
MECHANISM OF TRIGONAA ON THE URETER (Exparlmmtal
FIGURE
2.
perimental
154
INFLUENCE
Model)
Schematic model.
representation
of
basic
ex-
TRIGONE
EMG
Groups I, II, III, ZV, and V (A, B, C, D, FIGURE 3. E) evaluated role of nontrigonal, trigonal, and extravesical influences on ureter. Zn group V (E) electromyogram performed to investigate if trigonal contractile activity existed during bladder distention.
of the trigonal activity into the ureter occurred. This was evaluated by eliminating the obstructive influences on the intravesical segment with a diverting ureterotomy (vent) proximal to the ureterovesical junction. The extent of proximal transmission was assessed by creating ureteral vents in the middle and lower thirds of the ureter. Obstructive and conductive components of trigonal and nontrigonal intravesica1 factors were eliminated in group IV, to understand if any extravesical impulses (neurogenic) operated on the ureter during bladder distention and voiding. A submucous transection of the ureterotrigonal junction and an ipsilateral ureterotomy were performed in this group. In the group V experiments, attempts were made to record the electrica activity of the trigone during passive bladder distention. This was to evaluate if any trigonal activity resulted during passive bladder filling and if this activity was
UROLOGY
/
AUGUST
1973
/
VOLUME
II, NUMBER
2
responsible for the subtle ureteral changes that would usually be observed during the nonvoiding phase of bladder filling. Twenty-two adult mongrel dogs of both sexes, each one weighing 40 to 50 pounds, were used in this study and all were anesthetized with intravenous pentobarbital. The drug was administered intermittently through an intravenous saline drip. The ureter was exposed through a midline or lumbar incision and at a predetermined site; it was cannulated with a no. 5F polyethylene catheter. The ureter was connected by means of a T-shaped adaptor to a Harvard infusion pump-600 and a Statham strain gauge pressure transducer, P23AA. Recording was done on a Gilson M.5.P. Polygraph. Two polyethylene catheters of size 8 to 10F were introduced into the bladder through the dome and anchored to the wall. One was used to monitor the intravesical pressure and the other for filling and emptying the bladder. The effects of gradual filling and voiding contractions on the continuously infused ureter were observed. Quiescent phases of bladder filling and instantaneous voiding contractions were maneuvered by controlling the depth of anesthesia, the rate of bladder filling, and intermittent occlusion of urethra. In a group of 6 dogs (group I) the ureterotrigonal junction was exposed through a cystotomy and an incision was made in the mucosa and the trigonal muscle, 2 to 4 mm. distal to the ureteric orifice. The rent in the mucosa was closed with a fine running stitch. The ureter, therefore, was still attached to the bladder through the serous of this and mucous layers. The effectiveness ureterotrigonal muscular discontinuity was confirmed at the end of the experiment with anatomic dissections. The cystotomy opening was closed water tight. The ureteral activity was recorded during bladder distention and voiding contractions. Vesicoureteral reflux was ruled out by conducting the following urodynamic procedures. The ureteral activity was recorded with minimal or no flow through its lumen. During bladder filling, if any exaggerated peristaltic activity conforming to a pattern of changes in the intravesical pressure resulted, reflux was strongly suspected. This was confirmed by repeating the filling experiment with an occluding clamp, applied to the ureter proximal to the ureterovesical junction. The refluxing ureter would exhibit no such previously observed pressure activity. The ureteral changes would, however, reappear with bladder filling following removal of the occluding clamp. Electrical stimulation of trigone was performed after exposing the area of trigone through
UROLOGY
/
AUGUST
1973
I
VOLUME
II. NUMBER
2
a cystotomy. Biphasic square waves of 60 Hz. and 8.33 milliseconds with 8 to 10 volts were generated from an electrical stimulator of American Electronic Laboratories, model 104A. Other areas in the bladder detrusor were also stimulated (group II). In group III experiments ureterotomy was created to divert the flow from entering the intravesical ureter. The infusion flow was therefore prevented from being influenced by the obstructive components operating in the vicinity of the intravesical ureter. The ureterotomy was linearly placed and about 1 cm. in length. The edges were gently everted with a fine stitch for an effective diversion. The site of ureterotomy depended upon the level of the infusion catheter. A mid-third ureterotomy was made in the ureter with infusion conducted at the ureteropelvic junction. A vent in the distal third of the ureter was created, when the infusion was carried at the middle third of the ureter. Bladder filling experiments were conducted and the ureteral activity was recorded. A linear vent in the distal ureter was produced in dogs which were already subjected to an ipsilateral ureterotrigonal transection (group IV). Bladder filling experiments were performed in these models. Electrophysiological events were recorded during bladder distention on E.M.G. 21 of Gilson Medical Electronics. For convenience, female dogs were used in this study, and a total of 6 experiments were conducted. In 2 experiments, a linear vent in the ureter was also performed and recorded the ureteral activity simultaneously. Unipolar stainless steel suture electrode, insulated with a polyethylene tube, was sutured to the trigone intravesically, and the ends of the wire loop were brought out through the urethra. The activity in the trigone was monitored during passive bladder distention (group V). A total of 18 dogs were used in groups II, III, and V experiments. Results The antegrade polyethylene catheter recorded the ureteral peristalsis, in addition to being an infusion catheter. Increases in resting pressure, amplitude, and multiphasic contraction complexes were noticed in the ureter when the bladder was filled (Fig. 4A). Slow filling of the bladder with the dog maintained under deep anesthesia resulted in the ureter registering a slow and gradual rise in resting pressure followed by an increase in the
155
mm Hg 60
RIM;
mm Hg 60
;FllTER
60
60
w
-
20 0
AZ:-
REFLUXING
URETER CLAMP
PROXIMAL TO UVJ
CLAMPRELEASED NON REFLUXING
B
D
i
LJ
fllrnH@J
aor 60
URETER
NO
RIGHT URETER TRIGONAL INFLUENCE
mm Hq 7
a0 60
-
40 20 0
O-
ao-
LEFT TRIGONAL
60-
URETER INFLUENCE
ONLY
- 60 -40
4020
7 60
- 20
-
0 100
a0
I MIN I
- 60
604020 0
BLADDER
- 40 - 20 0
C FIGURE 4. Ureteral effects of bladder filling. (Ureteral infusion rate: 0.764 ml. per minute.) (A) Upper tracing: increase in ureteral activity caused by nontrigonal factors-even after ureterotrigonal junction (UTJ) was cut. Middle tracing: increase in resting pressure (resistance) and fusion of contraction complexes (multiphasic) of ureter. (B) Eflects of bladderfilling on refluxing ureter. Upper tracing shows pressure pattern in ureter similar to vesical pressure activity. Occlusion proximal to ureterovesical junction prevented these changes during bladder filling. Release of clamp resulted in exaggerated activity in ureter. (C) Ureteral activity as influenced. by nontrigonal and trigonal factors; increased ureteral activity demonstrated in both. Upper tracing shows changes in ureter with bladder filling without trigonal influence. Center tracing shows trigonal influence.
156
frequency of contraction complexes. Rapid filling of the bladder with the dog under light anesthesia produced an immediate voiding contraction. A sharp rise in the resting pressure, increase in frequency, and a tendency for fusion of contraction complexes were noticed during voiding. No vesicoureteral reflux resulted following transection of the ureterotrigonal junction. Figure 4B demonstrates the type of changes exhibited by a refluxing ureter. This reflux was incidentally observed in 3 dogs, which were not related to these experiments. Significant changes in the ureter were noticed in group I (ureterotrigonal junction transection) experiments during bladder filling and voiding (Fig. 4A,C). Elevated resting pressure and increase in frequency of contractions were observed consistently in all experiments. Electrical stimulation of the trigone (group II) produced changes in the ureter (Fig. 5A) in all experiments and these changes, although of less magnitude, could be reproduced in 8 out of 10 experiments, despite a linear vent (Fig. 5B). The effectiveness of the diverting vent was confirmed in this group of experiments by directly observing the ureteric orifice. No infusion flow was-seen emerging from the orifice into the bladder after creating the proximal ureteral vent. Ureteral vents (group III) created proximal to the ureterovesical junction did not prevent the onset of changes in ureteral activity during bladder filling, voiding, and electrical stimulation of trigone (Fig. 5B,C,D). However, the magnitude of changes were less, when compared with the effects observed in normal ureters. The activity was less pronounced in the upper ureters with mid-third ureteral vents. Maximum activity was noticed in the distal segments. No changes were demonstrated in the ureter subjected to trigonoureteral transection and ipsiIatera1 ureterotomy (group IV, Fig. 6). Electromyography of the bladder (group V) revealed that an increase in trigonal activity was noticed during passive bladder filling, while no significant changes in the vesical activity were demonstrated with conventional monitoring of the intravesical pressure (Fig. 7). Comment The popular views concerning the mechanisms responsible for changes in the ureteral activity concentrated on the ureterovesical junction and the effects exhibited were explained on the basis of obstruction. Tanagho3,sJo introduced a concept that an active trigonal contraction during micturition and a passive “stretch-obstruction” and
UROLOGY
/
AUGUST
1973
/
VOLUME
II, NUMBER
2
RIGHT URETER TRIGONAL INFLUENCE
OFF
A
TRlGONE STIMULATION
STIMULATION
so
TRIOONE STlYULATlON
BLADDER
60 40 10 0
ONLY
_/p”‘i.__ t
_._.
--
j;
._
L.“__--_..._-_4~-...
TRlSONE
EMS
FIGURE 6. Ureter devoid of trigonal and nontrigonal intravesical factors. Extravesical (neurogenic) factors exerted minimal influence on ureter during voiding. Upper tracing shows rise in ureteral resistance due to intact trigone. Middle tracing: no changes in ureter during bladder filling and voiding.
FIGURE 5. Ureteral eflects of electrical stimulation. (Square wave stimulus: 60 Hz., 8.3 milliseconds, and 5 to 8 V.) (A) Direct electrical trigone stimulation produced increased resistance, frequency, and amplitude of ureteral contraction complexes. Identical stimulus to adjacent detrusor produced no such changes. (Infusion rate: 1.91 ml. water per minute.) (B) Increase in ureteral resistance with trigonal stimulation despite ureteral vent proximal to ureterovesical junction (UVJ). These changes are of less magnitude when compared to activity in nonvented ureters (Fig. 5A). (C) Ureteral e$ects of rapid filling of bladder with dog under light anesthesia. (Ureteral infusion rate: 0.382 ml. per minute.) Diverting ureterotomy proximal to intravesical ureter did not prevent onset of ureteral changes when bladders werejilbed. This activity could have resulted from transmitted impulses from trigone or extravesical autonomic nervous factors. (D) Ureteral effects of bladderfilling and voiding after ureterotomy proximal to ureterovesical junction. (Infusion rate: 0.764 ml. per minute.) Increased activity in proximal ureter less obvious compared to changes in distal segment of same ureter.
change in tone in the intravesical ureter during prevoiding filling phase, would result in intravesical ureter obstruction. Kiil*,’ expressed that an increase in the intravesical pressure and compression of the intramural ureter by the detrusor contraction contributed to the increase in ureteral
UROLOGY
/ AUGUST
1973 / VOLUME
II, NUMBER
2
FIGURE 7. Electromyographic activity of during bladderjilling. Increased spike activity tude and frequency of action potentials) in during passive bladder filling demonstrated. tracing shows rise in infusion resistance after otomy. Middle tracing: no voiding contraction during stage of trigonal activity.
trigone (amplitrigone Upper ureternoted
resistance. He considered that the mechanical changes associated with distention of the bladder, namely, stretch and obliquity of the ureter and compression caused by the increase in bladder wall tension, produced intramural occlusion (Fig. 1). Fredericks et ~1.~~demonstrated the existence of an electrical continuity in the ureterotrigonal musculature by observing ureteral spike potentials conducted to the trigone. The results of our study confirmed the presence of a functional continuity between the ureter and trigone. The impulses generated in the trigone during voiding probably exerted a direct influence on the ureteral smooth muscle by proximal conduction. The less pronounced changes in the activity seen in the proximal segment of the ureter suggested that maximum conduction occurred in the ureter adjacent to the trigone and the conducted activity dissipated centrifugally. The ureteral activity at the ureterotrigonal junction probably also caused obstruction and accentuated the ureteral changes resulting from the conducted trigonal activity. The occurrence of
157
ureteral changes with bladder filling and voiding contractions despite a diverting vent proximal to the ureterovesical junction suggested that propagation of trigonal activity to the ureter occurred through the trigonoureteral muscular continuity. Elimination of the trigonal influence on the ureter did not prevent the onset of ureteral changes when the bladder was filled and voiding occurred. This only suggested that intravesical, nontrigonal factors additionally operated on the ureter. No changes were seen in the ureter when the bladder was filled in dogs which underwent diverting ureterotomy and ureterotrigonal transection (Fig. 6). This probably meant that extravesical neurogenic factors played a minimal role on the ureter during voiding contractions. The results of electrophysiologic studies revealed that spike activity occurred during quiescent filling phase of the bladder and this electrical activity could have contributed to the changes in the ureter demonstrated during passive bladder filling. The muscular response of the trigone must have been triggered by the multidirectional stretch caused during bladder filling. Graduate
Medical 419
Philadelphia,
Building
S. 19th Street
Pennsylvania (DR.
19146 YALLA)
ACKNOWLEDGMENT. We are grateful to Mr. Arthur Wagner, electronic engineer, and the technicians of the Bockus Research Institute, University of Pennsylvania, for their valuable heIp in conducting these experiments.
158
References 1. ZIMSKIND, P. D., DAVIS, D. M., and DECAESTECKER, J. E.: Effects of bladder filling on ureteral dynamics, J. Urol. 102: 693 (1969). The function of the Ureter and Renal Pelvis, 2. KIIL, F.: Philadelphia, W. B. Saunders Co., 1957. 3. TANAGHO, E. A., HUTCH, J. A., MEYERS, F. H., and RAMBO, 0. N., JR.: Primary vesicoureteral reflux: experimental studies of its etiology, J. Urol. 93: 165, (1965). 4. NOGRADY, M. D., DUNBAR, J. S., and MACEWAN, D. W.: The effects of (voluntary) bladder distension on the intravenous pyelogram. An experimental study, Am. J. Roentgenol. Radium Ther. Nucl. 90: 37 (1963). 5. ROSEN, K. I., CONSTANTINOU, C. E., SANDS, J. P., and GOVAN, D. W.: Dynamics of the upper urinary tract: effects of changes in bladder pressure on ureteral peristalsis, J. Urol. 106: 209 (1971). The dynamics of the ureterovesical and 6. HOMSY, G. E.: vesicourethral junctions. II. Effect of autonomic and somatic excitation on the resistance to flow of the distal ureter and lower urinary tract, Invest. Urol. 4: 408 (1967). 7. CAMPBELL, M. F., and HARRISON, J. H.: Urology, 3rd ed., Philadelphia, W. B. Saunders Co., 1970, vol. 1. 8. HAMILTON, W. J., BOYD, J. D., and MOSSMAN, H. W.: Human Embryology, Baltimore, The Williams &Wilkins co., 1952. The 9. TANACHO, E. A., MEYERS, F. H., and SMITH, D. R.: trigone: anatomical and physiological consideration. 1. In relation to the uretero-vesical junction, J. Urol. 100: 623 (1968). 10. TANAGHO, E. A., and PUGH, R. C. B.: The anatomy and function of the uretero-vesical junction, Brit. J. Urol. 35: 151 (1963). The 11. TANAGHO, E. A., SMITH, D. R., and MYERS, F. H.: trigone: anatomical and physiological considerations. 2. In relation to the bladder neck, J. Urol. 100: 633 (1968). 12. FREDERICKS, C. M., ANDERSON, G. F., and PIERCE, J. M.: In vivo extra-luminal bipolar recordings from the canine ureter and urinary bladder, Invest. Urol. 6: 284 (1968).
UROLOGY
/
AUGUST
1973
/
VOLUME
II, NUMBER 2
OF TRIGONAL
URETER
FILLING
DURING
AND
An Experimental SUBBARAO HARRY PAUL
V. YALLA,
INFLUENCE
BLADDER
VOIDING Study in Dogs M.D.
M. BURROS,
M.D.
D. ZIMSKIND,
M.D.
From the Departments of Urology, Graduate Hospital of the University of Pennsylvania, and Thomas Jefferson University
Hospital,
Philadelphia,
Pennsylvania
ABSTRACT-The role of the trigone and the mechanisms involved in its influence on the ureteral activity during bladder filling and voiding were investigated in 5 groups of adult mongrel dogs. The study included an evaluation of the influence of nontrigonal factors. Stimulation of the trigone with electric current and induced voiding was performed and the activity in the ureters in which linear vents were created proximal to the ureterovesical junction was monitored. Trigonal electromyography supplemented the studies. The results indicated that nontrigonal intravesical factors additionally operated on the ureter. The mechanism of the trigonal influence on the ureter was twofold. It produced maximal response at the ureterotrigonal junction causing obstruction at the terminal segment of the intravesical ureter. Second, the trigonal activity propagated proximally into the adjacent ureter, which thereby exhibited a direct smooth muscle response. Electromyographic studies of the trigone revealed increased spike activity even during nonvoiding stage of passive bladder filling.
The occurrence of changes in ureteral dynamics during bladder filling and voiding has been well documented with experimental and clinical studies.1-5 Obstruction at the ureterovesical junction was believed to cause these changes, and various intravesical factors were proposed by many workers (Fig. 1). Tanagho et al? suggested that the ureter was principally governed by the trigone during bladder filling and micturition, and they considered that the vesical factors mentioned by others played a minimal ro1e.2,6,7 The anatomic and embryologic studies reveaI that the trigone and the ureter are intimately related to each other. *ssA physiological syncitium probably exists in the trigonoureteral musculature, with these two structures either being interdependent or conjointly responding to the same stimuli. We believe the trigone influences the ureter directly, by virtue of its muscular activity transmitted proximally. It is known from other
UROLOGY
/ AUGUST
1973 / VOLUME
II, NUMBER
2
studies that the trigone actively contracts during voiding phase of micturition.g-ll The changes in
INTRAMURAL COYFRESSION OF THE URETER
II
BY
MTRUSOR CONTRACEQN (HOMSY)
:AL PRESSURE
INCREASE IN WALL TENSION
INCREASE SONAL STRETCH D CONTRACTION
FIGURE 1.
and site voiding.
IN OBLIOUITY
OF THE INTRAVESICAL URETER
Current concepts of obstructive factors of operation during bladder filling and
153
ureteral activity during voiding could, therefore, result from more than one mechanism governed by the trigone. This experimental study was aimed at investigating these possibilities and precisely evaluating the extent of trigonal influence on the ureter during bladder filling and micturition. Attempts were made to find out if any nontrigonal, intravesical factors additionally operated on the ureter. This study further attempted to probe if any trigonal activity existed during passive bladder filling phase and if this activity influenced the ureter.
ELECTRICAL STIMULATION OF EXPOSED TRIGONE
Material and Methods The experimental mode1 essentially consisted of antegrade ureteral infusion with a constant rate of saline and of recording the ureteral activity during bladder distention, voiding contractions, and electrical stimulation of the trigone (Fig. 2). were categorized into 5 The experiments groups (Fig. 3). In group I, attempts were made to evaluate the role of nontrigonal intravesical factors by eliminating the trigonal influences on the ureter. An intravesical, submucous transection of the ureterotrigonal junction was performed. Interpretation of the results was made after making certain that no vesicoureteral reflux resulted following ureterotrigonal discontinuity. In group II, direct application of the electric current on the exposed trigone was made. The changes in the ureter were entirely caused by the trigonal stimulation. For a comparison, nontrigonal areas on the bladder were also stimulated. Group III experiments evaluated the mechanism of trigonal influence on the ureter during trigonal electric stimulation, bladder distention, and voiding contraction. The experiments were conducted to investigate if any direct propagation THE
MECHANISM OF TRIGONAA ON THE URETER (Exparlmmtal
FIGURE
2.
perimental
154
INFLUENCE
Model)
Schematic model.
representation
of
basic
ex-
TRIGONE
EMG
Groups I, II, III, ZV, and V (A, B, C, D, FIGURE 3. E) evaluated role of nontrigonal, trigonal, and extravesical influences on ureter. Zn group V (E) electromyogram performed to investigate if trigonal contractile activity existed during bladder distention.
of the trigonal activity into the ureter occurred. This was evaluated by eliminating the obstructive influences on the intravesical segment with a diverting ureterotomy (vent) proximal to the ureterovesical junction. The extent of proximal transmission was assessed by creating ureteral vents in the middle and lower thirds of the ureter. Obstructive and conductive components of trigonal and nontrigonal intravesica1 factors were eliminated in group IV, to understand if any extravesical impulses (neurogenic) operated on the ureter during bladder distention and voiding. A submucous transection of the ureterotrigonal junction and an ipsilateral ureterotomy were performed in this group. In the group V experiments, attempts were made to record the electrica activity of the trigone during passive bladder distention. This was to evaluate if any trigonal activity resulted during passive bladder filling and if this activity was
UROLOGY
/
AUGUST
1973
/
VOLUME
II, NUMBER
2
responsible for the subtle ureteral changes that would usually be observed during the nonvoiding phase of bladder filling. Twenty-two adult mongrel dogs of both sexes, each one weighing 40 to 50 pounds, were used in this study and all were anesthetized with intravenous pentobarbital. The drug was administered intermittently through an intravenous saline drip. The ureter was exposed through a midline or lumbar incision and at a predetermined site; it was cannulated with a no. 5F polyethylene catheter. The ureter was connected by means of a T-shaped adaptor to a Harvard infusion pump-600 and a Statham strain gauge pressure transducer, P23AA. Recording was done on a Gilson M.5.P. Polygraph. Two polyethylene catheters of size 8 to 10F were introduced into the bladder through the dome and anchored to the wall. One was used to monitor the intravesical pressure and the other for filling and emptying the bladder. The effects of gradual filling and voiding contractions on the continuously infused ureter were observed. Quiescent phases of bladder filling and instantaneous voiding contractions were maneuvered by controlling the depth of anesthesia, the rate of bladder filling, and intermittent occlusion of urethra. In a group of 6 dogs (group I) the ureterotrigonal junction was exposed through a cystotomy and an incision was made in the mucosa and the trigonal muscle, 2 to 4 mm. distal to the ureteric orifice. The rent in the mucosa was closed with a fine running stitch. The ureter, therefore, was still attached to the bladder through the serous of this and mucous layers. The effectiveness ureterotrigonal muscular discontinuity was confirmed at the end of the experiment with anatomic dissections. The cystotomy opening was closed water tight. The ureteral activity was recorded during bladder distention and voiding contractions. Vesicoureteral reflux was ruled out by conducting the following urodynamic procedures. The ureteral activity was recorded with minimal or no flow through its lumen. During bladder filling, if any exaggerated peristaltic activity conforming to a pattern of changes in the intravesical pressure resulted, reflux was strongly suspected. This was confirmed by repeating the filling experiment with an occluding clamp, applied to the ureter proximal to the ureterovesical junction. The refluxing ureter would exhibit no such previously observed pressure activity. The ureteral changes would, however, reappear with bladder filling following removal of the occluding clamp. Electrical stimulation of trigone was performed after exposing the area of trigone through
UROLOGY
/
AUGUST
1973
I
VOLUME
II. NUMBER
2
a cystotomy. Biphasic square waves of 60 Hz. and 8.33 milliseconds with 8 to 10 volts were generated from an electrical stimulator of American Electronic Laboratories, model 104A. Other areas in the bladder detrusor were also stimulated (group II). In group III experiments ureterotomy was created to divert the flow from entering the intravesical ureter. The infusion flow was therefore prevented from being influenced by the obstructive components operating in the vicinity of the intravesical ureter. The ureterotomy was linearly placed and about 1 cm. in length. The edges were gently everted with a fine stitch for an effective diversion. The site of ureterotomy depended upon the level of the infusion catheter. A mid-third ureterotomy was made in the ureter with infusion conducted at the ureteropelvic junction. A vent in the distal third of the ureter was created, when the infusion was carried at the middle third of the ureter. Bladder filling experiments were conducted and the ureteral activity was recorded. A linear vent in the distal ureter was produced in dogs which were already subjected to an ipsilateral ureterotrigonal transection (group IV). Bladder filling experiments were performed in these models. Electrophysiological events were recorded during bladder distention on E.M.G. 21 of Gilson Medical Electronics. For convenience, female dogs were used in this study, and a total of 6 experiments were conducted. In 2 experiments, a linear vent in the ureter was also performed and recorded the ureteral activity simultaneously. Unipolar stainless steel suture electrode, insulated with a polyethylene tube, was sutured to the trigone intravesically, and the ends of the wire loop were brought out through the urethra. The activity in the trigone was monitored during passive bladder distention (group V). A total of 18 dogs were used in groups II, III, and V experiments. Results The antegrade polyethylene catheter recorded the ureteral peristalsis, in addition to being an infusion catheter. Increases in resting pressure, amplitude, and multiphasic contraction complexes were noticed in the ureter when the bladder was filled (Fig. 4A). Slow filling of the bladder with the dog maintained under deep anesthesia resulted in the ureter registering a slow and gradual rise in resting pressure followed by an increase in the
155
mm Hg 60
RIM;
mm Hg 60
;FllTER
60
60
w
-
20 0
AZ:-
REFLUXING
URETER CLAMP
PROXIMAL TO UVJ
CLAMPRELEASED NON REFLUXING
B
D
i
LJ
fllrnH@J
aor 60
URETER
NO
RIGHT URETER TRIGONAL INFLUENCE
mm Hq 7
a0 60
-
40 20 0
O-
ao-
LEFT TRIGONAL
60-
URETER INFLUENCE
ONLY
- 60 -40
4020
7 60
- 20
-
0 100
a0
I MIN I
- 60
604020 0
BLADDER
- 40 - 20 0
C FIGURE 4. Ureteral effects of bladder filling. (Ureteral infusion rate: 0.764 ml. per minute.) (A) Upper tracing: increase in ureteral activity caused by nontrigonal factors-even after ureterotrigonal junction (UTJ) was cut. Middle tracing: increase in resting pressure (resistance) and fusion of contraction complexes (multiphasic) of ureter. (B) Eflects of bladderfilling on refluxing ureter. Upper tracing shows pressure pattern in ureter similar to vesical pressure activity. Occlusion proximal to ureterovesical junction prevented these changes during bladder filling. Release of clamp resulted in exaggerated activity in ureter. (C) Ureteral activity as influenced. by nontrigonal and trigonal factors; increased ureteral activity demonstrated in both. Upper tracing shows changes in ureter with bladder filling without trigonal influence. Center tracing shows trigonal influence.
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frequency of contraction complexes. Rapid filling of the bladder with the dog under light anesthesia produced an immediate voiding contraction. A sharp rise in the resting pressure, increase in frequency, and a tendency for fusion of contraction complexes were noticed during voiding. No vesicoureteral reflux resulted following transection of the ureterotrigonal junction. Figure 4B demonstrates the type of changes exhibited by a refluxing ureter. This reflux was incidentally observed in 3 dogs, which were not related to these experiments. Significant changes in the ureter were noticed in group I (ureterotrigonal junction transection) experiments during bladder filling and voiding (Fig. 4A,C). Elevated resting pressure and increase in frequency of contractions were observed consistently in all experiments. Electrical stimulation of the trigone (group II) produced changes in the ureter (Fig. 5A) in all experiments and these changes, although of less magnitude, could be reproduced in 8 out of 10 experiments, despite a linear vent (Fig. 5B). The effectiveness of the diverting vent was confirmed in this group of experiments by directly observing the ureteric orifice. No infusion flow was-seen emerging from the orifice into the bladder after creating the proximal ureteral vent. Ureteral vents (group III) created proximal to the ureterovesical junction did not prevent the onset of changes in ureteral activity during bladder filling, voiding, and electrical stimulation of trigone (Fig. 5B,C,D). However, the magnitude of changes were less, when compared with the effects observed in normal ureters. The activity was less pronounced in the upper ureters with mid-third ureteral vents. Maximum activity was noticed in the distal segments. No changes were demonstrated in the ureter subjected to trigonoureteral transection and ipsiIatera1 ureterotomy (group IV, Fig. 6). Electromyography of the bladder (group V) revealed that an increase in trigonal activity was noticed during passive bladder filling, while no significant changes in the vesical activity were demonstrated with conventional monitoring of the intravesical pressure (Fig. 7). Comment The popular views concerning the mechanisms responsible for changes in the ureteral activity concentrated on the ureterovesical junction and the effects exhibited were explained on the basis of obstruction. Tanagho3,sJo introduced a concept that an active trigonal contraction during micturition and a passive “stretch-obstruction” and
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FIGURE 6. Ureter devoid of trigonal and nontrigonal intravesical factors. Extravesical (neurogenic) factors exerted minimal influence on ureter during voiding. Upper tracing shows rise in ureteral resistance due to intact trigone. Middle tracing: no changes in ureter during bladder filling and voiding.
FIGURE 5. Ureteral eflects of electrical stimulation. (Square wave stimulus: 60 Hz., 8.3 milliseconds, and 5 to 8 V.) (A) Direct electrical trigone stimulation produced increased resistance, frequency, and amplitude of ureteral contraction complexes. Identical stimulus to adjacent detrusor produced no such changes. (Infusion rate: 1.91 ml. water per minute.) (B) Increase in ureteral resistance with trigonal stimulation despite ureteral vent proximal to ureterovesical junction (UVJ). These changes are of less magnitude when compared to activity in nonvented ureters (Fig. 5A). (C) Ureteral e$ects of rapid filling of bladder with dog under light anesthesia. (Ureteral infusion rate: 0.382 ml. per minute.) Diverting ureterotomy proximal to intravesical ureter did not prevent onset of ureteral changes when bladders werejilbed. This activity could have resulted from transmitted impulses from trigone or extravesical autonomic nervous factors. (D) Ureteral effects of bladderfilling and voiding after ureterotomy proximal to ureterovesical junction. (Infusion rate: 0.764 ml. per minute.) Increased activity in proximal ureter less obvious compared to changes in distal segment of same ureter.
change in tone in the intravesical ureter during prevoiding filling phase, would result in intravesical ureter obstruction. Kiil*,’ expressed that an increase in the intravesical pressure and compression of the intramural ureter by the detrusor contraction contributed to the increase in ureteral
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FIGURE 7. Electromyographic activity of during bladderjilling. Increased spike activity tude and frequency of action potentials) in during passive bladder filling demonstrated. tracing shows rise in infusion resistance after otomy. Middle tracing: no voiding contraction during stage of trigonal activity.
trigone (amplitrigone Upper ureternoted
resistance. He considered that the mechanical changes associated with distention of the bladder, namely, stretch and obliquity of the ureter and compression caused by the increase in bladder wall tension, produced intramural occlusion (Fig. 1). Fredericks et ~1.~~demonstrated the existence of an electrical continuity in the ureterotrigonal musculature by observing ureteral spike potentials conducted to the trigone. The results of our study confirmed the presence of a functional continuity between the ureter and trigone. The impulses generated in the trigone during voiding probably exerted a direct influence on the ureteral smooth muscle by proximal conduction. The less pronounced changes in the activity seen in the proximal segment of the ureter suggested that maximum conduction occurred in the ureter adjacent to the trigone and the conducted activity dissipated centrifugally. The ureteral activity at the ureterotrigonal junction probably also caused obstruction and accentuated the ureteral changes resulting from the conducted trigonal activity. The occurrence of
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ureteral changes with bladder filling and voiding contractions despite a diverting vent proximal to the ureterovesical junction suggested that propagation of trigonal activity to the ureter occurred through the trigonoureteral muscular continuity. Elimination of the trigonal influence on the ureter did not prevent the onset of ureteral changes when the bladder was filled and voiding occurred. This only suggested that intravesical, nontrigonal factors additionally operated on the ureter. No changes were seen in the ureter when the bladder was filled in dogs which underwent diverting ureterotomy and ureterotrigonal transection (Fig. 6). This probably meant that extravesical neurogenic factors played a minimal role on the ureter during voiding contractions. The results of electrophysiologic studies revealed that spike activity occurred during quiescent filling phase of the bladder and this electrical activity could have contributed to the changes in the ureter demonstrated during passive bladder filling. The muscular response of the trigone must have been triggered by the multidirectional stretch caused during bladder filling. Graduate
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Philadelphia,
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ACKNOWLEDGMENT. We are grateful to Mr. Arthur Wagner, electronic engineer, and the technicians of the Bockus Research Institute, University of Pennsylvania, for their valuable heIp in conducting these experiments.
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References 1. ZIMSKIND, P. D., DAVIS, D. M., and DECAESTECKER, J. E.: Effects of bladder filling on ureteral dynamics, J. Urol. 102: 693 (1969). The function of the Ureter and Renal Pelvis, 2. KIIL, F.: Philadelphia, W. B. Saunders Co., 1957. 3. TANAGHO, E. A., HUTCH, J. A., MEYERS, F. H., and RAMBO, 0. N., JR.: Primary vesicoureteral reflux: experimental studies of its etiology, J. Urol. 93: 165, (1965). 4. NOGRADY, M. D., DUNBAR, J. S., and MACEWAN, D. W.: The effects of (voluntary) bladder distension on the intravenous pyelogram. An experimental study, Am. J. Roentgenol. Radium Ther. Nucl. 90: 37 (1963). 5. ROSEN, K. I., CONSTANTINOU, C. E., SANDS, J. P., and GOVAN, D. W.: Dynamics of the upper urinary tract: effects of changes in bladder pressure on ureteral peristalsis, J. Urol. 106: 209 (1971). The dynamics of the ureterovesical and 6. HOMSY, G. E.: vesicourethral junctions. II. Effect of autonomic and somatic excitation on the resistance to flow of the distal ureter and lower urinary tract, Invest. Urol. 4: 408 (1967). 7. CAMPBELL, M. F., and HARRISON, J. H.: Urology, 3rd ed., Philadelphia, W. B. Saunders Co., 1970, vol. 1. 8. HAMILTON, W. J., BOYD, J. D., and MOSSMAN, H. W.: Human Embryology, Baltimore, The Williams &Wilkins co., 1952. The 9. TANACHO, E. A., MEYERS, F. H., and SMITH, D. R.: trigone: anatomical and physiological consideration. 1. In relation to the uretero-vesical junction, J. Urol. 100: 623 (1968). 10. TANAGHO, E. A., and PUGH, R. C. B.: The anatomy and function of the uretero-vesical junction, Brit. J. Urol. 35: 151 (1963). The 11. TANAGHO, E. A., SMITH, D. R., and MYERS, F. H.: trigone: anatomical and physiological considerations. 2. In relation to the bladder neck, J. Urol. 100: 633 (1968). 12. FREDERICKS, C. M., ANDERSON, G. F., and PIERCE, J. M.: In vivo extra-luminal bipolar recordings from the canine ureter and urinary bladder, Invest. Urol. 6: 284 (1968).
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