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Dynamics of the Ureterovesical Junction; A Qualitative Analysis of the Ureterovesical Pressure Profile in the Pig
0022-534 7/85/1344-0818$02.00/0 Vol. 134, October Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1985 by The Williams & Wilkins Co.
DYNAMICS OF THE URETEROVESICAL JUNCTION; A QUALITATIVE ANALYSIS OF THE URETEROVESICAL PRESSURE PROFILE IN THE PIG CEES BLOK,* GERE. P. M. VAN VENROOIJ
AND
BO L. R. A. COOLSAET
From the Department of Urology, Academic Hospital, Utrecht, The Netherlands
ABSTRACT
In pigs, ureterovesical pressure profiles were analyzed by combined prevesical perfusion pressure measurement and microsensor pressure profilometry of the ureterovesical junction, which showed comparable and reproducible fast and slow pressure waves. Cystoscopy revealed that the fast pressure waves were associated with fluid spurts from the ureteral orifice and wrinkling of bladder mucosa over the ureterovesical junction. During slow pressure waves only initial decreases in outflow from the orifice may occur. After dissection of the detrusor muscle at the UVJ only fast pressure waves were recorded. At similar pressure measurements on an inactivated ureter segment which was obliquely passed through the bladder wall only slow pressure waves could be detected. It is concluded that the fast pressure waves of the ureterovesical pressure profile represent peristaltic activity which is generated at the ureterovesical junction and by which fluid may be discharged into the bladder. The slow pressure waves of the pressure profile reflect impairment of flow through the ureterovesical junction by detrusor activity. High pressure bladders and large volume low pressure bladders, with or without infravesical obstruction, may be associated with wide upper urinary tracts, maldevelopment and morphological changes of the kidneys, and deterioration of renal function. 1-9The possible causes of these phenomena are incompetence of the antireflux mechanism of the ureterovesical junction (UVJ) with vesicoureteral reflux and/ or impairment to urinary outflow from the upper urinary tract. It has been postulated that such impairment to flow through the UV J is functional in origin as no intraluminal obstructive lesions have been found within the UVJ. 2 However, morphologic changes of the ureteral sheaths are described in "megaureters," which might contribute to the impairment of flow through the UVJ in a full bladder. 10 Also the dimensions and dynamics of the normal upper urinary tract and therewith renal function are influenced by bladder filling volume. 11 The results of pressure flow studies of the upper urinary tract depend on bladder filling volume and intravesical pressure. 12 The apparent relationship between function and geometry of the bladder and function of the upper urinary tract illustrates the clinical significance of the dynamics of the UVJ. The dynamics of the UVJ have been evaluated by sidehole13-15 or open-end2· 16' 17 perfusion pressure measurements, and by combined manometric and electromyographic studies. 18 Conclusions based on the results of these measurements are controversial. The development of ureteral peristaltic activity at the UVJ 18· 19 and the presence of a pressure profile at the UVJ when the bladder is empty13· 15 have been advocated or denied. Some conclusions are hypothetical. Near the UVJ a biphasic pressure profile has been described of which the pressure_increases are attributed to prevesical ureteral sphincter activity and passage of the side-hole of the measuring catheter through the ureteral orifice. 13 Anatomical and urodynamical considerations. At the UVJ the most distal ureteral segment obliquely traverses the bladder wall and ultimately runs submucosally parallel to the bladder mucosa before it reaches the ureteral orifice. 20 Three ureteral Accepted for publication May 31, 1985. * Requests for reprints: Slotervaart Ziekenhuis, Dept. of Urology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. 818
segments are distinguished at the UVJ, namely, the juxtavesical, the intramural, and the submucosal ureteral segment. These three ureteral segments are enveloped in two muscular ureteral sheaths which juxtavesically extend along the ureter for 3 to 4 cm. and distally extend into the trigone. 21 ·22 From the anatomy of the UVJ it may be expected that the pressure phenomena within the UVJ ureteral segment may result from: - the passive and active properties of the wall of the UVJ ureter segments and their sheaths; forces in the bladder wall around the UVJ; - intravesical pressure which is transmitted upon the wall of the submucosal and intramural ureter segments; - propagation of prevesical ureteral peristalsis. The aim of our investigation was to analyze the ureterovesical pressure profile (UVPP) by evaluating the contribution of these anatomical structures and dynamical factors to the pressure phenomena of the UV J. This was done by the principle of elimination and addition. MATERIALS AND METHODS
The experiments were performed on 16 female landrace pigs (16 to 30 kg.) under general anesthesia with parenteral Stresnil and Hypnodil, and artificial respiration with N 20/0 2 mixtures. In order to analyze and validate the pressure profilometry of the UVJ during fluid transport, simultaneously prevesical perfusion pressure measurements (Pp) and intraluminal microsensor pressure measurements (P.) of the UVJ were performed. Figure 1 schematically shows the experimental set-up. The urinary tract was exposed via a midabdominal incision. A FlO flexible polyethylene end-hole catheter, inner diameter 2 mm., was introduced into a ureter via a distal longitudinal ureterotomy. This catheter was positioned with its end-hole at 3 to 4 cm. proximally to the bladder wall and fixed with a ligature. The ureteral segment which contained the perfusion catheter was contused with a clamp before the catheter was introduced. This manoeuvre eliminates instantaneously and completely the activity of the ureteral wall for at least 5 hours without causing leakage through the wall during perfusion. 23 The proximal end of the FlO catheter was covered with a rubber cap through which a G14 infusion needle and an F5 micro pressure-sensor
819
URETEROVESICAL PRESSURE PROFILE IN THE PIG
IP
FIG. 2. Perfusion pressure measurement and microsensor pressure measurement on inactivated ureter segment, which is obliquely passed through bladder wall.
s Fm. 1. Schematic view of experimental set-up. IP = infusion pump; PT= physiological pressure transducer; P 0 = perfusion pressure; P, = microsensor pressure; P 8 = bladder pressure; C = cystoscope; MS = micro pressure-sensor element; S = syringe. Upper blow-up shows combined introduction of perfusion line and micro pressure sensor catheter into FlO catheter. Lower blow-up shows pressure measuring method.
catheter (Philips Honeywell, type MTC/P5FE) were introduced into the system. Via a three-way connecting piece the infusion needle was connected with a Braun UNITA IA infusion pump and a Hewlett-Packard physiological pressure transducer. A Ch 19 cytoscope with 30° optics was introduced into the bladder via the urethra. Bladder filling volumes were regulated via the cytoscope. Bladder pressure was measured via an F5 end-side-hole catheter (AHS International) which was introduced via the cystoscope and which also was connected with a Hewlett-Packard physiological pressure transducer. Measured pressures were registrated on a Polygraph or a HewlettPackard recorder. U reteral and bladder pressures were measured during ureteral perfusion with methylene blue colored normal saline at increasing perfusion rates and at different bladder filling volumes. During these measurements the ureteral orifice was continuously observed. Ureteral perfusion pressure measurements were performed under three different conditions: Group 1. Through an intact UVJ of all 16 pigs. Group 2. After elimination of detrusor activity. For this purpose the detrusor muscle was dissected from the superficial ureteral sheath in 6 systems. Magnifying glasses were used during this dissection. Group 3. After elimination of the activity of the UVJ ureter segment and its sheaths, and addition of detrusor activity. For this purpose in 4 pigs a midureter segment with a length of about 5 cm. was resected, contused and obliquely passed through the bladder wall (fig. 2).
RESULTS
Group 1. In all 16 UVJs combined prevesical perfusion (Pp) and intraluminal microsensor pressures (P.) simultaneously showed comparable fast and slow pressure waves, which were similar when the micropressure sensor was located near the endhole of the perfusion catheter (fig. 3). Comparable pressure waves were recorded at step-wise microsensor pressure profilometry during nonperfusion (fig. 4). Endoscopy revealed that during a fast pressure wave fluid may spurt out of the ureteral orifice. At the end of this fluid spurt wrinkling of bladder mucosa over the UVJ occurred. Such mucosa! wrinkling, which is most clearly visible via a cystotomy, also occurred at the end of a fast pressure wave which was not accompanied by fluid discharge from the orifice. In 8 systems, with intraluminal microsensor pressure measurement of the UVJ, a decrease of the frequency of the fast pressure waves occurred once UVJ perfusion started (fig. 5). In 5 systems, with intraluminal UVJ microsensor pressure measurement and nonperfusion, the frequency of the fast pressure waves was inversely related to the bladder filling volume (fig. 6). Slow pressure waves were neither accompanied by a fluid spurt from the ureteral orifice nor by wrinkling of bladder mucosa. On the contrary, especially at lower perfusion rates (<0.1 ml./min.) an initial decrease in outflow from the orifice during these slow pressure waves could be observed. At increasing perfusion rates both basal UVJ perfusion pressure as well as the amplitudes of the slow pressure waves increased (fig. 7A). Within the submucosal (fig. 4) and juxtavesical ureteral segments, no slow pressure waves were recorded with the micro pressure-sensor during nonperfusion. At nonperfusion, intraluminal UVJ microsensor baseline pressure was highest in the intramural ureteral segment in the unexpanded bladder (fig. 4). Once the bladder was so far filled that it was expanded, such baseline pressure was highest in the submucosal ureteral segment. Group 2. In 5 systems out of 6, after isolation of the UVJ · from the detrusor muscle, only fast pressure waves with fluid
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spurts from the orifice were observed (fig. 7B). In one system no pressure waves at all could be detected. Even after complete resection of the UVJ after 4 to 6 hours of experimentation, in 2 specimens spontaneous, and in 3
specimens mechanically induced peristaltic pressure waves with fluid spurts from the orifice were detected during intraluminal and perfusion pressure measurement (fig. 8). Group 3. In all 4 contused and transplanted midureter seg-
821
Fm. 5. Simultaneous registration of UVJ perfusion pressure UVJ. Note decrease of frequency of fast pressure waves once
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FIG. 6. With intraluminal UVJ micro-sensor pressure measurement and nonperfusion, frequency of fast pressure waves is inversely related to bladder filling volume.
822
BLOK, VAN VENROOIJ AND COOLSAET
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FIG. 7. A, three successive perfusion pressure measurements (Pp) at different perfusion rates. Note increase of baseline pressure and increase of amplitudes of slow P-waves at increasing ureteral perfusion rates. B, perfusion pressure measurement after near complete dissection of detrusor muscle from UVJ. Note near absence of slow P-waves.
ments only slow pressure waves were recorded (fig. 9). These slow pressure waves resembled those measured at the intact UVJ and they also showed increase of amplitudes at increasing ureteral perfusion rates (fig. 9). DISCUSSION
Prevesical UVJ perfusion pressure measurement without any catheter within the UVJ showed fast and slow pressure waves comparable to microsensor pressure profilometry of the UVJ during nonperfusion. This indicates that these pressure waves more likely originated from muscular activity, rather than from a merely passive mechanical resistance to passage of a catheter through the UVJ.
Within the UVJ, fast pressure waves, in contrast with slow ones, occurred simultaneously with a fluid spurt from the ureteral orifice at the end of which wrinkling of bladder mucosa over the UVJ occurred. Such mucosal wrinkling also occurred in association with a fast pressure wave which was not accompanied by a fluid spurt. These findings indicate that fast pressure waves of the UVPP represent peristaltic activity which is generated by the UVJ ureter segment and/or its sheaths, and by which a fluid bolus may be discharged into the bladder. The more so as these phenomena persisted after elimination of detrusor activity. Therefore the conclusion of Tsuchida18 that the UVJ does not develop ureteral peristaltic activity on its own is in contradiction with our findings and also with his own
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823
upper upper tract then may be Slow pressure waves represented the influence of detrusor activity upon flow through the as they disappeared from the pressure curves after the detrusor muscle was dissected from the superficial ureteral sheath. The more so, as during perfusion of an inactivated ureter segment which is obliquely passed through the bladder wall only slow pressure waves were recorded, which were comparable to those found at the intact UV J and which showed the same characteristics. As the slow pressure waves originated from the intramural ureteral segment, they obviously represented squeezing of this segment by the surrounding detrusor muscle bundles at the urete:ric hiatus. Such squeezing initially contributes to emptying of the UVJ ureter segment and subsequently increases resistance to flow through the UVJ. Basal perfusion pressure of the UVJ, and thus baseline pressure of the UVPP, reflects the resistance to flow through the UVJ as it increases with increasing perfusion rates. As the UV J ureteral segment develops peristaltic activity, a catheter within its lumen, as in the ureter, may interfere with ureteral wall activity and induce peristalsis, 24 especially when such a catheter also is moved within the UVJ. Such interference then depends on the size and flexibility of the catheter, the withdrawal velocity of the catheter and the curvature of the UVJ. Due to a whip effect, a flexible catheter which is withdrawn at high velocity through a curved ureteral segment behaves like a less flexible one and therefore increases mechanically induced activity at the UVJ. Bladder filling and/or perfusion of the UVJ reduced artificially induced activity, as is demonstrated by our results (figs. 5 and 6). Perfusion of the UVJ reduces the contact between the pressure measuring catheter and the ureteral wall by embedding the catheter within a fluid bolus. This also applies to bladder filling, as this improves the alignment of the ureteral wall along the catheter at the UVJ. Therefore ureterovesical pressure profilometry at higher perfusion rates(;;,, l ml./min.) with intermittent or low withdrawal velocity of the measuring catheter is recommended, as it reduces artificially induced peristalsis and provides highly reproducible UVPP's. High withdrawal velocity of the measuring catheter through the UVJ should be rejected as it may artificially induce activity and, on the other hand, slow pressure waves, and therefore the influence of detrusor on UVJ flow dynamics may be missed. m,,Gvicmu;; to the anatomy of the it is difficult if not uuµu,,N,cm:: to measure an exact UVPP, and n<>nn~m a UV J pressure measurement or isolate the with its ureteral sheaths. This is because the UV J exwrms the ureter which is surrounded the ureteral sheaths. sheaths gradually change into the adventitia and ureteric muscularis. The site at this occurs can be determined by dissection. 22 Macroscopic dissection can only be performed easily at the space between the ureteral sheaths, as these are loosely connected with each other. On the contrary, the detrusor and the ureteric muscularis are quite firmly connected respectively, the superficial and the deep ureteral sheaths.
FIG.
pressure registration curve which shows activity and not a silent baseline pressure. Obviously the UVJ can develop peristaltic activity autonomously, as even after complete isolation fast pressure waves could be recorded within its lumen. This may be of clinical significance for urinary transport in the patient with a wide,
CONCLUSIONS
The ureterovesical pressure profile shows: a baseline pressure which represents resistance to flow through the UV J; fast pressure waves which represent peristaltic activity of the UVJ ureteral segment by which fluid may be discharged from the UVJ into the bladder; slow pressure waves which represent the influence of detrusor activity upon flow through the UVJ;
824
BLOK, VAN VENROOIJ AND COOLSAET
artificially induced activity which may be due to the presence of an intralu:rhinal catheter. The applicability and value of ureterovesical pressure profilometry in clinical practice needs to be further evaluated. Before this can be done the UVPP should be analyzed for characteristics which represent the efficiency of peristaltic fluid discharge from the UVJ. Also the fluid transport mechanism at the UV J and the factors which determine the resistance to UVJ flow (the baseline pressure of the UVPP) should be known. Acknowledgments. The authors wish to acknowledge the help of Dan Gil and co-workers of the Central Animal Laboratory. REFERENCES 1. Hutch, J. A. and Tanagho, E. A.: Etiology of non-occlusive ureteral dilatation. J. Urol., 93: 177, 1965. 2. Backlund, L. and Reuterskiold, A. G.: The abnormal ureter in children. Scand. J. Urol. Nephrol., 3: 219, 1969. 3. Koff; S. A., Lapides, J. and Piazza, D. H.: The uninhibited bladder in children: a cause for urinary obstruction, infection and reflux. In: Reflux Nephropathy. Edited by J. Hodson and P. KincaidSmith. Masson Publishing, U.S.A., p. 161. 1979. 4. Osterhage, H. R.: Uber die Auswirkungen von Hiirnrohrenstenosen auf den oberen Harntrakt. F. K. Schattauerverlag, Stuttgart, 1981. 5. Hald, T. and Bradley, W. E.: The Urinary Bladder. Williams & Wilkins Company, Baltimore, London, 1982. 6. Ransley, P. G.: Vesicoureteric reflux. In: Upper Urinary Tract Obstruction in Pediatric Urology. Edited by D. I. Williams and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 151, 1982. 7. Johhston, J. H.: Upper Urinary Tract Obstructions in Pediatric Urology. Edited by D. I. Williams and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 189, 1982. 8. Johnston, J. H.: Bladder disorders. In: Upper Urinary Tract Obstruction in Pediatric Urology. Edited by: D. I. Williams and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 225, 1982. 9. Williams, D. I.: Male urethral obstructions. In: Upper Urinary Tract Obstruction in Pediatric Urology. Edited by D. I. Williams
10.
11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
22. 23.
24.
and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 251, 1982. Tokunaka, S. and Koyanagi, T.: Morphologic study of primary nonreflux megaureters with particular emphasis on the role of ureteral sheath ancl ureteral dysplasia. J. Urol., 128: 399, 1982. Zimskind, P. D., Davis, D. M. and Decaestecker, J. E.: Effects of bladder filling on ureteral dynamics. J. Urol., 102: 693, 1969. Coolsaet, B. L. R. A., Venrooij, G. E. P. M. van and Blok, C.: The ureterovesical pressure profile. Abstracts, 77th Annual Meeting of the ADA, Kansas City, May 16-20, p. 180, 1982. Bruynes, E.: The ureteral pressure profile. Ural. Int., 33: 381, 1978. Weiss, R. M., and Biancani, P.: Characteristics of normal and refluxing ureterovesical junctions. Abstracts, third meeting ISDU, Aarhus, Denmark, August 31-September 1, 1981. Leen, G. L., Fegetter, J. G. W. and Stobbart, D.: The ureterovesical pressure profile: fact or fiction. Abstracts fourth meeting ISDU, Utrecht, The Netherlands, August 29-September 1, 1982. Tanagho, E. A., Meyers, F. H. and Smith, D. R.: The trigone: anatomical and physiological considerations in relation to the ureterovesical junction. J. Urol., 100: 623, 1968. McGuire, E. J., Woodside, J. R. and Borden, Th. A.: Upper urinary tract deterioration in patients with myelodysplasia and detrusor hypertonia: a follow-up study. J. Urol., 129: 823, 1983. Tsuchida, S. and Kimura, Y.: Vesicoureteral reflux. Tohoku J. Exp. Med., 91: 1, 1967. Mathisen, W.: Vesicoureteral reflux and its surgical correction. Surg. Gynecol. Obstet., 118: 965, 1964. Tanagho, E. R. and Pugh, R. C. B.: The anatomy and function of the ureterovesical junction. Brit. J. Urol., 35: 151, 1963. Elbadawi, A., Amaku, E. 0. and Frank, I. N.: Anatomy of the submucosal segment of the ureter. Read at the annual meeting of the Northeastern section of the AUA. Quebec City, Quebec, September 1969. Elbadawi, A.: Anatomy and function of the ureteral sheaths. J. Urol., 102: 224, 1972. Blok, C., Venrooij, G. E. P. M. van and Coolsaet, B. L. R. A.: Active urine transport through the ureterovesical junction. Abstracts fourth meeting ISDU, Utrecht, The Netherlands, August 29September 1, 1982. Weinberg, S. L.: Ureteral function. The ureteral catheter and the urometrogram. Invest. Urol., 12: 255, 1975.
THE JOURNAL OF UROLOGY
Copyright © 1985 by The Williams & Wilkins Co.
DYNAMICS OF THE URETEROVESICAL JUNCTION; A QUALITATIVE ANALYSIS OF THE URETEROVESICAL PRESSURE PROFILE IN THE PIG CEES BLOK,* GERE. P. M. VAN VENROOIJ
AND
BO L. R. A. COOLSAET
From the Department of Urology, Academic Hospital, Utrecht, The Netherlands
ABSTRACT
In pigs, ureterovesical pressure profiles were analyzed by combined prevesical perfusion pressure measurement and microsensor pressure profilometry of the ureterovesical junction, which showed comparable and reproducible fast and slow pressure waves. Cystoscopy revealed that the fast pressure waves were associated with fluid spurts from the ureteral orifice and wrinkling of bladder mucosa over the ureterovesical junction. During slow pressure waves only initial decreases in outflow from the orifice may occur. After dissection of the detrusor muscle at the UVJ only fast pressure waves were recorded. At similar pressure measurements on an inactivated ureter segment which was obliquely passed through the bladder wall only slow pressure waves could be detected. It is concluded that the fast pressure waves of the ureterovesical pressure profile represent peristaltic activity which is generated at the ureterovesical junction and by which fluid may be discharged into the bladder. The slow pressure waves of the pressure profile reflect impairment of flow through the ureterovesical junction by detrusor activity. High pressure bladders and large volume low pressure bladders, with or without infravesical obstruction, may be associated with wide upper urinary tracts, maldevelopment and morphological changes of the kidneys, and deterioration of renal function. 1-9The possible causes of these phenomena are incompetence of the antireflux mechanism of the ureterovesical junction (UVJ) with vesicoureteral reflux and/ or impairment to urinary outflow from the upper urinary tract. It has been postulated that such impairment to flow through the UV J is functional in origin as no intraluminal obstructive lesions have been found within the UVJ. 2 However, morphologic changes of the ureteral sheaths are described in "megaureters," which might contribute to the impairment of flow through the UVJ in a full bladder. 10 Also the dimensions and dynamics of the normal upper urinary tract and therewith renal function are influenced by bladder filling volume. 11 The results of pressure flow studies of the upper urinary tract depend on bladder filling volume and intravesical pressure. 12 The apparent relationship between function and geometry of the bladder and function of the upper urinary tract illustrates the clinical significance of the dynamics of the UVJ. The dynamics of the UVJ have been evaluated by sidehole13-15 or open-end2· 16' 17 perfusion pressure measurements, and by combined manometric and electromyographic studies. 18 Conclusions based on the results of these measurements are controversial. The development of ureteral peristaltic activity at the UVJ 18· 19 and the presence of a pressure profile at the UVJ when the bladder is empty13· 15 have been advocated or denied. Some conclusions are hypothetical. Near the UVJ a biphasic pressure profile has been described of which the pressure_increases are attributed to prevesical ureteral sphincter activity and passage of the side-hole of the measuring catheter through the ureteral orifice. 13 Anatomical and urodynamical considerations. At the UVJ the most distal ureteral segment obliquely traverses the bladder wall and ultimately runs submucosally parallel to the bladder mucosa before it reaches the ureteral orifice. 20 Three ureteral Accepted for publication May 31, 1985. * Requests for reprints: Slotervaart Ziekenhuis, Dept. of Urology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. 818
segments are distinguished at the UVJ, namely, the juxtavesical, the intramural, and the submucosal ureteral segment. These three ureteral segments are enveloped in two muscular ureteral sheaths which juxtavesically extend along the ureter for 3 to 4 cm. and distally extend into the trigone. 21 ·22 From the anatomy of the UVJ it may be expected that the pressure phenomena within the UVJ ureteral segment may result from: - the passive and active properties of the wall of the UVJ ureter segments and their sheaths; forces in the bladder wall around the UVJ; - intravesical pressure which is transmitted upon the wall of the submucosal and intramural ureter segments; - propagation of prevesical ureteral peristalsis. The aim of our investigation was to analyze the ureterovesical pressure profile (UVPP) by evaluating the contribution of these anatomical structures and dynamical factors to the pressure phenomena of the UV J. This was done by the principle of elimination and addition. MATERIALS AND METHODS
The experiments were performed on 16 female landrace pigs (16 to 30 kg.) under general anesthesia with parenteral Stresnil and Hypnodil, and artificial respiration with N 20/0 2 mixtures. In order to analyze and validate the pressure profilometry of the UVJ during fluid transport, simultaneously prevesical perfusion pressure measurements (Pp) and intraluminal microsensor pressure measurements (P.) of the UVJ were performed. Figure 1 schematically shows the experimental set-up. The urinary tract was exposed via a midabdominal incision. A FlO flexible polyethylene end-hole catheter, inner diameter 2 mm., was introduced into a ureter via a distal longitudinal ureterotomy. This catheter was positioned with its end-hole at 3 to 4 cm. proximally to the bladder wall and fixed with a ligature. The ureteral segment which contained the perfusion catheter was contused with a clamp before the catheter was introduced. This manoeuvre eliminates instantaneously and completely the activity of the ureteral wall for at least 5 hours without causing leakage through the wall during perfusion. 23 The proximal end of the FlO catheter was covered with a rubber cap through which a G14 infusion needle and an F5 micro pressure-sensor
819
URETEROVESICAL PRESSURE PROFILE IN THE PIG
IP
FIG. 2. Perfusion pressure measurement and microsensor pressure measurement on inactivated ureter segment, which is obliquely passed through bladder wall.
s Fm. 1. Schematic view of experimental set-up. IP = infusion pump; PT= physiological pressure transducer; P 0 = perfusion pressure; P, = microsensor pressure; P 8 = bladder pressure; C = cystoscope; MS = micro pressure-sensor element; S = syringe. Upper blow-up shows combined introduction of perfusion line and micro pressure sensor catheter into FlO catheter. Lower blow-up shows pressure measuring method.
catheter (Philips Honeywell, type MTC/P5FE) were introduced into the system. Via a three-way connecting piece the infusion needle was connected with a Braun UNITA IA infusion pump and a Hewlett-Packard physiological pressure transducer. A Ch 19 cytoscope with 30° optics was introduced into the bladder via the urethra. Bladder filling volumes were regulated via the cytoscope. Bladder pressure was measured via an F5 end-side-hole catheter (AHS International) which was introduced via the cystoscope and which also was connected with a Hewlett-Packard physiological pressure transducer. Measured pressures were registrated on a Polygraph or a HewlettPackard recorder. U reteral and bladder pressures were measured during ureteral perfusion with methylene blue colored normal saline at increasing perfusion rates and at different bladder filling volumes. During these measurements the ureteral orifice was continuously observed. Ureteral perfusion pressure measurements were performed under three different conditions: Group 1. Through an intact UVJ of all 16 pigs. Group 2. After elimination of detrusor activity. For this purpose the detrusor muscle was dissected from the superficial ureteral sheath in 6 systems. Magnifying glasses were used during this dissection. Group 3. After elimination of the activity of the UVJ ureter segment and its sheaths, and addition of detrusor activity. For this purpose in 4 pigs a midureter segment with a length of about 5 cm. was resected, contused and obliquely passed through the bladder wall (fig. 2).
RESULTS
Group 1. In all 16 UVJs combined prevesical perfusion (Pp) and intraluminal microsensor pressures (P.) simultaneously showed comparable fast and slow pressure waves, which were similar when the micropressure sensor was located near the endhole of the perfusion catheter (fig. 3). Comparable pressure waves were recorded at step-wise microsensor pressure profilometry during nonperfusion (fig. 4). Endoscopy revealed that during a fast pressure wave fluid may spurt out of the ureteral orifice. At the end of this fluid spurt wrinkling of bladder mucosa over the UVJ occurred. Such mucosa! wrinkling, which is most clearly visible via a cystotomy, also occurred at the end of a fast pressure wave which was not accompanied by fluid discharge from the orifice. In 8 systems, with intraluminal microsensor pressure measurement of the UVJ, a decrease of the frequency of the fast pressure waves occurred once UVJ perfusion started (fig. 5). In 5 systems, with intraluminal UVJ microsensor pressure measurement and nonperfusion, the frequency of the fast pressure waves was inversely related to the bladder filling volume (fig. 6). Slow pressure waves were neither accompanied by a fluid spurt from the ureteral orifice nor by wrinkling of bladder mucosa. On the contrary, especially at lower perfusion rates (<0.1 ml./min.) an initial decrease in outflow from the orifice during these slow pressure waves could be observed. At increasing perfusion rates both basal UVJ perfusion pressure as well as the amplitudes of the slow pressure waves increased (fig. 7A). Within the submucosal (fig. 4) and juxtavesical ureteral segments, no slow pressure waves were recorded with the micro pressure-sensor during nonperfusion. At nonperfusion, intraluminal UVJ microsensor baseline pressure was highest in the intramural ureteral segment in the unexpanded bladder (fig. 4). Once the bladder was so far filled that it was expanded, such baseline pressure was highest in the submucosal ureteral segment. Group 2. In 5 systems out of 6, after isolation of the UVJ · from the detrusor muscle, only fast pressure waves with fluid
820
BLOK, VAN VENROOIJ AND COOLSAET
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30 S
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FIG. 3. Results of combined prevesical UVJ perfusion (Pp) and intraluminal UVJ microsensor (P,) pressure measurements.
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305 FIG. 4. Microsensor pressure (P,) measurement at three different locations in UVJ during nonperfusion at empty bladder. Note absence of slow P-waves at submucosal ureteral segment and highest baseline pressure within intramural ureteral segment.
spurts from the orifice were observed (fig. 7B). In one system no pressure waves at all could be detected. Even after complete resection of the UVJ after 4 to 6 hours of experimentation, in 2 specimens spontaneous, and in 3
specimens mechanically induced peristaltic pressure waves with fluid spurts from the orifice were detected during intraluminal and perfusion pressure measurement (fig. 8). Group 3. In all 4 contused and transplanted midureter seg-
821
Fm. 5. Simultaneous registration of UVJ perfusion pressure UVJ. Note decrease of frequency of fast pressure waves once
p
intravesical pressure (PB) and intraluminal microsensor pressure (P,) of started.
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FIG. 6. With intraluminal UVJ micro-sensor pressure measurement and nonperfusion, frequency of fast pressure waves is inversely related to bladder filling volume.
822
BLOK, VAN VENROOIJ AND COOLSAET
PERFUSION: 0.30 ML/MIN 40 .
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FIG. 7. A, three successive perfusion pressure measurements (Pp) at different perfusion rates. Note increase of baseline pressure and increase of amplitudes of slow P-waves at increasing ureteral perfusion rates. B, perfusion pressure measurement after near complete dissection of detrusor muscle from UVJ. Note near absence of slow P-waves.
ments only slow pressure waves were recorded (fig. 9). These slow pressure waves resembled those measured at the intact UVJ and they also showed increase of amplitudes at increasing ureteral perfusion rates (fig. 9). DISCUSSION
Prevesical UVJ perfusion pressure measurement without any catheter within the UVJ showed fast and slow pressure waves comparable to microsensor pressure profilometry of the UVJ during nonperfusion. This indicates that these pressure waves more likely originated from muscular activity, rather than from a merely passive mechanical resistance to passage of a catheter through the UVJ.
Within the UVJ, fast pressure waves, in contrast with slow ones, occurred simultaneously with a fluid spurt from the ureteral orifice at the end of which wrinkling of bladder mucosa over the UVJ occurred. Such mucosal wrinkling also occurred in association with a fast pressure wave which was not accompanied by a fluid spurt. These findings indicate that fast pressure waves of the UVPP represent peristaltic activity which is generated by the UVJ ureter segment and/or its sheaths, and by which a fluid bolus may be discharged into the bladder. The more so as these phenomena persisted after elimination of detrusor activity. Therefore the conclusion of Tsuchida18 that the UVJ does not develop ureteral peristaltic activity on its own is in contradiction with our findings and also with his own
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s FIG. 8. Simultaneous registration of perfusion pressure (Pp) and intraluminal microsensor pressure (P 8 ) of mechanically induced activity in completely resected UVJ.
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ML/MIN 9. Perfusion pressure measurement through contused and transplanted midureter segment at increasing perfusion rates. Note increase of amplitudes of slow P-waves.
'THE: PiG
823
upper upper tract then may be Slow pressure waves represented the influence of detrusor activity upon flow through the as they disappeared from the pressure curves after the detrusor muscle was dissected from the superficial ureteral sheath. The more so, as during perfusion of an inactivated ureter segment which is obliquely passed through the bladder wall only slow pressure waves were recorded, which were comparable to those found at the intact UV J and which showed the same characteristics. As the slow pressure waves originated from the intramural ureteral segment, they obviously represented squeezing of this segment by the surrounding detrusor muscle bundles at the urete:ric hiatus. Such squeezing initially contributes to emptying of the UVJ ureter segment and subsequently increases resistance to flow through the UVJ. Basal perfusion pressure of the UVJ, and thus baseline pressure of the UVPP, reflects the resistance to flow through the UVJ as it increases with increasing perfusion rates. As the UV J ureteral segment develops peristaltic activity, a catheter within its lumen, as in the ureter, may interfere with ureteral wall activity and induce peristalsis, 24 especially when such a catheter also is moved within the UVJ. Such interference then depends on the size and flexibility of the catheter, the withdrawal velocity of the catheter and the curvature of the UVJ. Due to a whip effect, a flexible catheter which is withdrawn at high velocity through a curved ureteral segment behaves like a less flexible one and therefore increases mechanically induced activity at the UVJ. Bladder filling and/or perfusion of the UVJ reduced artificially induced activity, as is demonstrated by our results (figs. 5 and 6). Perfusion of the UVJ reduces the contact between the pressure measuring catheter and the ureteral wall by embedding the catheter within a fluid bolus. This also applies to bladder filling, as this improves the alignment of the ureteral wall along the catheter at the UVJ. Therefore ureterovesical pressure profilometry at higher perfusion rates(;;,, l ml./min.) with intermittent or low withdrawal velocity of the measuring catheter is recommended, as it reduces artificially induced peristalsis and provides highly reproducible UVPP's. High withdrawal velocity of the measuring catheter through the UVJ should be rejected as it may artificially induce activity and, on the other hand, slow pressure waves, and therefore the influence of detrusor on UVJ flow dynamics may be missed. m,,Gvicmu;; to the anatomy of the it is difficult if not uuµu,,N,cm:: to measure an exact UVPP, and n<>nn~m a UV J pressure measurement or isolate the with its ureteral sheaths. This is because the UV J exwrms the ureter which is surrounded the ureteral sheaths. sheaths gradually change into the adventitia and ureteric muscularis. The site at this occurs can be determined by dissection. 22 Macroscopic dissection can only be performed easily at the space between the ureteral sheaths, as these are loosely connected with each other. On the contrary, the detrusor and the ureteric muscularis are quite firmly connected respectively, the superficial and the deep ureteral sheaths.
FIG.
pressure registration curve which shows activity and not a silent baseline pressure. Obviously the UVJ can develop peristaltic activity autonomously, as even after complete isolation fast pressure waves could be recorded within its lumen. This may be of clinical significance for urinary transport in the patient with a wide,
CONCLUSIONS
The ureterovesical pressure profile shows: a baseline pressure which represents resistance to flow through the UV J; fast pressure waves which represent peristaltic activity of the UVJ ureteral segment by which fluid may be discharged from the UVJ into the bladder; slow pressure waves which represent the influence of detrusor activity upon flow through the UVJ;
824
BLOK, VAN VENROOIJ AND COOLSAET
artificially induced activity which may be due to the presence of an intralu:rhinal catheter. The applicability and value of ureterovesical pressure profilometry in clinical practice needs to be further evaluated. Before this can be done the UVPP should be analyzed for characteristics which represent the efficiency of peristaltic fluid discharge from the UVJ. Also the fluid transport mechanism at the UV J and the factors which determine the resistance to UVJ flow (the baseline pressure of the UVPP) should be known. Acknowledgments. The authors wish to acknowledge the help of Dan Gil and co-workers of the Central Animal Laboratory. REFERENCES 1. Hutch, J. A. and Tanagho, E. A.: Etiology of non-occlusive ureteral dilatation. J. Urol., 93: 177, 1965. 2. Backlund, L. and Reuterskiold, A. G.: The abnormal ureter in children. Scand. J. Urol. Nephrol., 3: 219, 1969. 3. Koff; S. A., Lapides, J. and Piazza, D. H.: The uninhibited bladder in children: a cause for urinary obstruction, infection and reflux. In: Reflux Nephropathy. Edited by J. Hodson and P. KincaidSmith. Masson Publishing, U.S.A., p. 161. 1979. 4. Osterhage, H. R.: Uber die Auswirkungen von Hiirnrohrenstenosen auf den oberen Harntrakt. F. K. Schattauerverlag, Stuttgart, 1981. 5. Hald, T. and Bradley, W. E.: The Urinary Bladder. Williams & Wilkins Company, Baltimore, London, 1982. 6. Ransley, P. G.: Vesicoureteric reflux. In: Upper Urinary Tract Obstruction in Pediatric Urology. Edited by D. I. Williams and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 151, 1982. 7. Johhston, J. H.: Upper Urinary Tract Obstructions in Pediatric Urology. Edited by D. I. Williams and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 189, 1982. 8. Johnston, J. H.: Bladder disorders. In: Upper Urinary Tract Obstruction in Pediatric Urology. Edited by: D. I. Williams and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 225, 1982. 9. Williams, D. I.: Male urethral obstructions. In: Upper Urinary Tract Obstruction in Pediatric Urology. Edited by D. I. Williams
10.
11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
22. 23.
24.
and J. H. Johnston. 2nd ed., Butterworth Scientific, London, p. 251, 1982. Tokunaka, S. and Koyanagi, T.: Morphologic study of primary nonreflux megaureters with particular emphasis on the role of ureteral sheath ancl ureteral dysplasia. J. Urol., 128: 399, 1982. Zimskind, P. D., Davis, D. M. and Decaestecker, J. E.: Effects of bladder filling on ureteral dynamics. J. Urol., 102: 693, 1969. Coolsaet, B. L. R. A., Venrooij, G. E. P. M. van and Blok, C.: The ureterovesical pressure profile. Abstracts, 77th Annual Meeting of the ADA, Kansas City, May 16-20, p. 180, 1982. Bruynes, E.: The ureteral pressure profile. Ural. Int., 33: 381, 1978. Weiss, R. M., and Biancani, P.: Characteristics of normal and refluxing ureterovesical junctions. Abstracts, third meeting ISDU, Aarhus, Denmark, August 31-September 1, 1981. Leen, G. L., Fegetter, J. G. W. and Stobbart, D.: The ureterovesical pressure profile: fact or fiction. Abstracts fourth meeting ISDU, Utrecht, The Netherlands, August 29-September 1, 1982. Tanagho, E. A., Meyers, F. H. and Smith, D. R.: The trigone: anatomical and physiological considerations in relation to the ureterovesical junction. J. Urol., 100: 623, 1968. McGuire, E. J., Woodside, J. R. and Borden, Th. A.: Upper urinary tract deterioration in patients with myelodysplasia and detrusor hypertonia: a follow-up study. J. Urol., 129: 823, 1983. Tsuchida, S. and Kimura, Y.: Vesicoureteral reflux. Tohoku J. Exp. Med., 91: 1, 1967. Mathisen, W.: Vesicoureteral reflux and its surgical correction. Surg. Gynecol. Obstet., 118: 965, 1964. Tanagho, E. R. and Pugh, R. C. B.: The anatomy and function of the ureterovesical junction. Brit. J. Urol., 35: 151, 1963. Elbadawi, A., Amaku, E. 0. and Frank, I. N.: Anatomy of the submucosal segment of the ureter. Read at the annual meeting of the Northeastern section of the AUA. Quebec City, Quebec, September 1969. Elbadawi, A.: Anatomy and function of the ureteral sheaths. J. Urol., 102: 224, 1972. Blok, C., Venrooij, G. E. P. M. van and Coolsaet, B. L. R. A.: Active urine transport through the ureterovesical junction. Abstracts fourth meeting ISDU, Utrecht, The Netherlands, August 29September 1, 1982. Weinberg, S. L.: Ureteral function. The ureteral catheter and the urometrogram. Invest. Urol., 12: 255, 1975.