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Artificial exstrophy in the dog for separated renal function studies
ARTIFICIAL
EXSTROPHY RENAL RICHARD
IN FUNCTION L.
STUDIES OF RENAL FUNCTION frequently require separate collection from the two kidneys in order to assess effect of control and experimental conditions in the same animal. The chronic study of separate renal function before and after a given intervention has been hampered by lack of suitable chronic preparations for individual kidney urine collections. We have compared five previously described methods [l, 3-61 for preparing animals for chronic separate renal function study with the artificial exstrophy bladder preparation We have found the procedure of artificial bladder trigone exstrophy to have significant advantages over these previously described methods for the chronic study of separate kidney function in the dog. The technique for bladder trigone exstrophy will be described in detail and comparison with our experience with other methods will be described. TECHNIQUE Surgery Female dogs weighing more than 15 kg. were anesthetized with sodium pentobarbitalf From the Urology Service, Walter Reed General Hospital, Washington, D.C. 20012. Submitted for publication June 13, 1968. *Address after July 1, 1968: Department of Urology, University of Miami School of Medicine, Jackson Memorial Hospital, Miami, Florida. fveterinary Laboratories, Inc., Kansas City, Missouri.
THE
FEIN,
DOG FOR STUDIES
SEPARATED
M.D.*
(30 mg. per kilogram I.V.) and placed in the supine position. The abdomen was opened through a 6-8 cm. midline suprapubic incision starting at the symphysis pubis (Fig. la). The bladder was identified, freed of its fibrous attachments, and delivered onto the abdominal wall. Urine was removed from the bladder. The urethra was freed from the vagina and divided between clamps at the bladder neck (Fig. lb). The bladder was opened bv a ventral longitudinal incision starting at’ the urethral opening of the bladder neck (Fig. lc) which exposed the bladder trigone and ureteral orifices. All of the bladder was then dissected off, leaving only the bladder trigone attached to the ureters and the blood supply (Figs. Id and e) [2]. An elliptical piece of all layers of the abdominal wall was resected from each side of the incision such that in suturing the exteriorized bladder trigone to the skin the bladder is stretched flat. The anastomosis was performed with interrupted 2-O chromic catgut sutures (Fig. If). The trigone usually was found to fill the small elliptical abdominal wall defect so that no closure of the abdominal wall layers was necessary. If the incision was larger than the stretched-out trigone, the rectus muscle and fascia were closed with interrupted 2-O chromic catgut until the trigone filled the abdominal wall defect. We have found it important to exteriorize only the trigone of the bladder and suture it flat and taut to the abdominal wall just cranial to 235
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
g
NO.
4,
APRIL
1969
Collection Approximately 1 week was required for healing, maturation of the ureteral orifices, and to allow sufficient time for the effect of the surgical procedure on renal function to be dissipated. Immediately postoperatively, a traumatic catheterization was required to insert even an 8 French catheter into a ureter which would easily accept a 14 French red rubber Robinson catheter 7 days postoperation. For collection, in order to obtain an atraumatic snug ureteral fit without urine leakage or hematuria, the ureteral orifice was gradually dilated with increasing sizes of welllubricated straight, round-ended red rubber Robinson catheters until a very snug fit was obtained (Fig. lg). Then the same size Robinson catheter with a beveled end was inserted about 10 cm. into the ureter. This catheter was secured to the abdominal wall with a 2-O silk suture and placed into a suitable collecting device (Fig. lh). This prevents ureteral peristalsis from extruding the catheter. There is no residual urine in the catheters since they are essentially similarsized straight extensions of the ureter. Care of the Animals
Fig. 1. a, Suprapubic incision; b, Exteriorized bladder with urethra being divided between clamps; c, Opened bladder exposing the trigone and ureteral orifices; d and e, Bladder dissected off leaving only the trigone; f, Trigone sutured to elliptical abdominal wall defect; g, Ureteral catheters; h, Urine collection.
the symphysis pubis in order to prevent herniation and/or retraction of the bladder trigone. No postoperative care was found necessary. 236
Animals given absolutely no care except at the time of repeat studies maintained an adequate trigone bladder preparation for 34 months. For periods longer than this it was found best to have the animals kept in cages with good drainage; occasional animals were able to clean the trigone area adequately themselves for prolonged periods without care. With cage drainage, the trigone bladder preparation will probably stay useful for as long as required for chronic studies. We have maintained animals for 9 months with such preparations without complications. Figure 2 shows such a trigone bladder 9 months after operation. If the animals were housed where there was no drainage and were required to lie in their urine for long periods, a severe ammoniacal dermatitis often developed. This represents a minimal problem when it involves only the skin (Fig. 3), but with extension onto the bladder trigone (Fig. 4), the ureteral orifices often became ob-
FEIN:
Fig. 2.
A 7-month
exstrophy
ARTIFICIAL
EXSTROPHY
IX
RENrZL
FUNCTIOS
STUDIES
preparation,
Fig. 4. trigone.
Severe
dermatitis
encroaching
onto
Fig. 3. Six-month preparation showing normal exstrophied bladder with surrounding ammoniacal dermatitis. strutted, dilated, for catheterization
RESULTS
and could not be identified ( Fig.
AND
5).
DISCUSSION
The artificial exstrophy trigone bladder preparation described above was used in 14
Fig. 5. Dilated structed ureteral dermatitis.
ureters behind partially oborifices secondary to severe 237
JOURNAL
OF SURGICAL
RESEARCH
VOL.
g NO.
female dogs weighing more than 15 kg. Repeat individual renal clearance studies were performed over a period of 3 months. There were no problems with catheterization of the ureters, urine leakage, trigonitis, hematuria, sepsis, or pyelonephritis. The renal clearances of creatinine, para-aminohippurate for glomerular filtration rate and effective renal plasma flow and osmolar clearance and free water clearance were essentially equal between the two kidneys. Six dogs were then kept for a period of 6-9 months. Four of these developed severe ammoniacal dermatitis while being housed on cement runs. The other two dogs managed to keep themselves clean. The dermatitis markedly improved in three of the dogs once they were placed in drainage cages. In one (Figs. 4 and 5) ureteral obstruction developed from the dermatitis involving the trigone. The results of the individual renal clearance studies in the five preparations in which the ureters could still be catheterized, again, were equal. The five previously described methods [l, 3-61 for preparing animals for chronic separated renal function study were compared with the current method of artificial bladder exstrophy. Various complications of these five preparations significantly hampered attempted chronic studies of individual kidney function. End cutaneous ureterostomies [4] failed because of stricture or contraction of the stoma or encroachment of skin onto the orifices. A bifid bladder preparation [3] presented multiple problems: The technique of preparation was difficult; correct identification of the bladder halves was difficult; urine collection was often a problem since catheters were often expelled; the catheter balloon occluded the ureteral orifice; or the hemibladder served as a variable reservoir. The DeSautels [l] hemisection of the bladder served well for chronic experiments lasting less than 4 weeks. However, the technique of preparation is not simple, moderate blood loss attends the surgical procedure, and the two cystostomy tubes serve as chronic foreign bodies. The cystostomy tubes tended to retract under the skin and become obstructed; if pulled on by the animal, leakage occurred around the tube 238
4,
APRIL
1969
or a true fistula resulted. Daily attention was required to prevent mucoid plugging of even large catheters and to recognize and repair fistulas. Manziano and King [6] have described a method for producing a split bladder around a special stainless-steel and Teflon prosthesis. Our experience with this technique again revealed the problems of an indwelling foreign body, a cannula that required meticulous attention to prevent plugging, and a variable bladder reservoir that obviated quantitatively accurate urine collection. Maluf [5] has described a method for exteriorizing the entire bladder and closing the abdominal wall beneath it. We have found that such a preparation may cause obstruction of the ureter, either retraction or hemiation of the bladder, and much difficulty in catheterizing the ureters because of the redundant bladder mucosa. Maluf did not catheterize the ureters, but collected the urine by means of glass suction tubes. In our hands, such a collection method often led to excessive loss of urine. SUMMARY A simple artificial exstrophy trigone bladder preparation for performing separate renal function studies has been described. It requires no special surgical skill to perform, uses no foreign bodies, requires minimal care to maintain, and provides for simple, nontraumatic, repetitive ureteral catheterizations with or without anesthesia. The main principles of the surgical technique involve exteriorization of only the trigone of the bladder and taut suture of the trigone to a small elliptical skin incision placed just cranial to the symphysis pubis. Urine is collected by snug-fitting catheters which are inserted after gradual nontraumatic dilatation of the ureters. REFERENCES 1. DeSautels, R. E. Hemisection of the bladder for the collection of separate urine samples. Surg. Gynec. Obstet. 105:767, 1957. 2. Dragstedt, C. A., and Dragstedt, L. R. A method for studying the secretion of urine in experimental animals. .l. Lab. Clin. Med. 13:688, 1928.
FEIS:
3.
Holt, M. H., Mantini, E. L., and Warden, H. E. A bifid bladder preparation for experimental split function renal studies. J. Surg. Res. 4:43, 1964. 4. Hudson, P. B., Wolan, C. T., and Marden, H. E. Technic for one-stage tube cutaneous ureterostomy. Ann. Surg. 142:257, 1955.
ARTIFICIAL
EXSTROPHY
IN
RENAL
FUNCTION
STUDIES
5.
Maluf, N. S. R. Exteriorization of the canine vesical trigone for experiments on the kidney. Ann. Surg. 130:43, 1949. 6. Manziano, C. F., and King, A. An operation to study split-renal function in brief and long-term experiments in dogs. J. Snrg. Res. 6:537, 1966.
239
EXSTROPHY RENAL RICHARD
IN FUNCTION L.
STUDIES OF RENAL FUNCTION frequently require separate collection from the two kidneys in order to assess effect of control and experimental conditions in the same animal. The chronic study of separate renal function before and after a given intervention has been hampered by lack of suitable chronic preparations for individual kidney urine collections. We have compared five previously described methods [l, 3-61 for preparing animals for chronic separate renal function study with the artificial exstrophy bladder preparation We have found the procedure of artificial bladder trigone exstrophy to have significant advantages over these previously described methods for the chronic study of separate kidney function in the dog. The technique for bladder trigone exstrophy will be described in detail and comparison with our experience with other methods will be described. TECHNIQUE Surgery Female dogs weighing more than 15 kg. were anesthetized with sodium pentobarbitalf From the Urology Service, Walter Reed General Hospital, Washington, D.C. 20012. Submitted for publication June 13, 1968. *Address after July 1, 1968: Department of Urology, University of Miami School of Medicine, Jackson Memorial Hospital, Miami, Florida. fveterinary Laboratories, Inc., Kansas City, Missouri.
THE
FEIN,
DOG FOR STUDIES
SEPARATED
M.D.*
(30 mg. per kilogram I.V.) and placed in the supine position. The abdomen was opened through a 6-8 cm. midline suprapubic incision starting at the symphysis pubis (Fig. la). The bladder was identified, freed of its fibrous attachments, and delivered onto the abdominal wall. Urine was removed from the bladder. The urethra was freed from the vagina and divided between clamps at the bladder neck (Fig. lb). The bladder was opened bv a ventral longitudinal incision starting at’ the urethral opening of the bladder neck (Fig. lc) which exposed the bladder trigone and ureteral orifices. All of the bladder was then dissected off, leaving only the bladder trigone attached to the ureters and the blood supply (Figs. Id and e) [2]. An elliptical piece of all layers of the abdominal wall was resected from each side of the incision such that in suturing the exteriorized bladder trigone to the skin the bladder is stretched flat. The anastomosis was performed with interrupted 2-O chromic catgut sutures (Fig. If). The trigone usually was found to fill the small elliptical abdominal wall defect so that no closure of the abdominal wall layers was necessary. If the incision was larger than the stretched-out trigone, the rectus muscle and fascia were closed with interrupted 2-O chromic catgut until the trigone filled the abdominal wall defect. We have found it important to exteriorize only the trigone of the bladder and suture it flat and taut to the abdominal wall just cranial to 235
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
g
NO.
4,
APRIL
1969
Collection Approximately 1 week was required for healing, maturation of the ureteral orifices, and to allow sufficient time for the effect of the surgical procedure on renal function to be dissipated. Immediately postoperatively, a traumatic catheterization was required to insert even an 8 French catheter into a ureter which would easily accept a 14 French red rubber Robinson catheter 7 days postoperation. For collection, in order to obtain an atraumatic snug ureteral fit without urine leakage or hematuria, the ureteral orifice was gradually dilated with increasing sizes of welllubricated straight, round-ended red rubber Robinson catheters until a very snug fit was obtained (Fig. lg). Then the same size Robinson catheter with a beveled end was inserted about 10 cm. into the ureter. This catheter was secured to the abdominal wall with a 2-O silk suture and placed into a suitable collecting device (Fig. lh). This prevents ureteral peristalsis from extruding the catheter. There is no residual urine in the catheters since they are essentially similarsized straight extensions of the ureter. Care of the Animals
Fig. 1. a, Suprapubic incision; b, Exteriorized bladder with urethra being divided between clamps; c, Opened bladder exposing the trigone and ureteral orifices; d and e, Bladder dissected off leaving only the trigone; f, Trigone sutured to elliptical abdominal wall defect; g, Ureteral catheters; h, Urine collection.
the symphysis pubis in order to prevent herniation and/or retraction of the bladder trigone. No postoperative care was found necessary. 236
Animals given absolutely no care except at the time of repeat studies maintained an adequate trigone bladder preparation for 34 months. For periods longer than this it was found best to have the animals kept in cages with good drainage; occasional animals were able to clean the trigone area adequately themselves for prolonged periods without care. With cage drainage, the trigone bladder preparation will probably stay useful for as long as required for chronic studies. We have maintained animals for 9 months with such preparations without complications. Figure 2 shows such a trigone bladder 9 months after operation. If the animals were housed where there was no drainage and were required to lie in their urine for long periods, a severe ammoniacal dermatitis often developed. This represents a minimal problem when it involves only the skin (Fig. 3), but with extension onto the bladder trigone (Fig. 4), the ureteral orifices often became ob-
FEIN:
Fig. 2.
A 7-month
exstrophy
ARTIFICIAL
EXSTROPHY
IX
RENrZL
FUNCTIOS
STUDIES
preparation,
Fig. 4. trigone.
Severe
dermatitis
encroaching
onto
Fig. 3. Six-month preparation showing normal exstrophied bladder with surrounding ammoniacal dermatitis. strutted, dilated, for catheterization
RESULTS
and could not be identified ( Fig.
AND
5).
DISCUSSION
The artificial exstrophy trigone bladder preparation described above was used in 14
Fig. 5. Dilated structed ureteral dermatitis.
ureters behind partially oborifices secondary to severe 237
JOURNAL
OF SURGICAL
RESEARCH
VOL.
g NO.
female dogs weighing more than 15 kg. Repeat individual renal clearance studies were performed over a period of 3 months. There were no problems with catheterization of the ureters, urine leakage, trigonitis, hematuria, sepsis, or pyelonephritis. The renal clearances of creatinine, para-aminohippurate for glomerular filtration rate and effective renal plasma flow and osmolar clearance and free water clearance were essentially equal between the two kidneys. Six dogs were then kept for a period of 6-9 months. Four of these developed severe ammoniacal dermatitis while being housed on cement runs. The other two dogs managed to keep themselves clean. The dermatitis markedly improved in three of the dogs once they were placed in drainage cages. In one (Figs. 4 and 5) ureteral obstruction developed from the dermatitis involving the trigone. The results of the individual renal clearance studies in the five preparations in which the ureters could still be catheterized, again, were equal. The five previously described methods [l, 3-61 for preparing animals for chronic separated renal function study were compared with the current method of artificial bladder exstrophy. Various complications of these five preparations significantly hampered attempted chronic studies of individual kidney function. End cutaneous ureterostomies [4] failed because of stricture or contraction of the stoma or encroachment of skin onto the orifices. A bifid bladder preparation [3] presented multiple problems: The technique of preparation was difficult; correct identification of the bladder halves was difficult; urine collection was often a problem since catheters were often expelled; the catheter balloon occluded the ureteral orifice; or the hemibladder served as a variable reservoir. The DeSautels [l] hemisection of the bladder served well for chronic experiments lasting less than 4 weeks. However, the technique of preparation is not simple, moderate blood loss attends the surgical procedure, and the two cystostomy tubes serve as chronic foreign bodies. The cystostomy tubes tended to retract under the skin and become obstructed; if pulled on by the animal, leakage occurred around the tube 238
4,
APRIL
1969
or a true fistula resulted. Daily attention was required to prevent mucoid plugging of even large catheters and to recognize and repair fistulas. Manziano and King [6] have described a method for producing a split bladder around a special stainless-steel and Teflon prosthesis. Our experience with this technique again revealed the problems of an indwelling foreign body, a cannula that required meticulous attention to prevent plugging, and a variable bladder reservoir that obviated quantitatively accurate urine collection. Maluf [5] has described a method for exteriorizing the entire bladder and closing the abdominal wall beneath it. We have found that such a preparation may cause obstruction of the ureter, either retraction or hemiation of the bladder, and much difficulty in catheterizing the ureters because of the redundant bladder mucosa. Maluf did not catheterize the ureters, but collected the urine by means of glass suction tubes. In our hands, such a collection method often led to excessive loss of urine. SUMMARY A simple artificial exstrophy trigone bladder preparation for performing separate renal function studies has been described. It requires no special surgical skill to perform, uses no foreign bodies, requires minimal care to maintain, and provides for simple, nontraumatic, repetitive ureteral catheterizations with or without anesthesia. The main principles of the surgical technique involve exteriorization of only the trigone of the bladder and taut suture of the trigone to a small elliptical skin incision placed just cranial to the symphysis pubis. Urine is collected by snug-fitting catheters which are inserted after gradual nontraumatic dilatation of the ureters. REFERENCES 1. DeSautels, R. E. Hemisection of the bladder for the collection of separate urine samples. Surg. Gynec. Obstet. 105:767, 1957. 2. Dragstedt, C. A., and Dragstedt, L. R. A method for studying the secretion of urine in experimental animals. .l. Lab. Clin. Med. 13:688, 1928.
FEIS:
3.
Holt, M. H., Mantini, E. L., and Warden, H. E. A bifid bladder preparation for experimental split function renal studies. J. Surg. Res. 4:43, 1964. 4. Hudson, P. B., Wolan, C. T., and Marden, H. E. Technic for one-stage tube cutaneous ureterostomy. Ann. Surg. 142:257, 1955.
ARTIFICIAL
EXSTROPHY
IN
RENAL
FUNCTION
STUDIES
5.
Maluf, N. S. R. Exteriorization of the canine vesical trigone for experiments on the kidney. Ann. Surg. 130:43, 1949. 6. Manziano, C. F., and King, A. An operation to study split-renal function in brief and long-term experiments in dogs. J. Snrg. Res. 6:537, 1966.
239