Canine Ureter Research Articles

Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle

Since, in the human ureter, both β2- and β3-adrenoceptors mediate adrenergic-stimulation-induced relaxation, selective β2-/β3-adrenoceptor agonists might prove clinically useful for relieving ureteral colic and promoting stone passage. We evaluated the β-adrenoceptor subtype selectivity and ureteral-relaxing efficacy of (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid (KUL-7211), a new β-adrenoceptor agonist, in vitro. In rat isolated organs, its selectivities, for inhibition of spontaneous uterine contraction (mediated via β2-adrenergic stimulation) and inhibition of colonic contraction (via β3-adrenergic stimulation) versus increase in atrial rate (via β1-adrenergic stimulation), were 56.3 and 242.2, respectively. KUL-7211 relaxed 80-mM-KCl-induced tonic contractions in both rabbit (pD2 value: 5.86 ± 0.13, whose ureteral relaxation is mediated via β2-adrenergic stimulation) and canine (pD2 value: 6.52 ± 0.16, via β3-adrenergic stimulation) isolated ureters in a concentration-dependent manner. These KUL-7211-induced relaxing effects were antagonized by ICI-118,551 (selective β2-adrenoceptor antagonist, pKB value: 8.91 ± 0.24) in the rabbit ureter and by bupranolol (non-selective β-adernoceptor antagonist, pKB value: 6.85 ± 0.12) in the canine ureter. KUL-7211 also reduced the spontaneous rhythmic contraction in a canine ureteral spiral preparation in a concentration-dependent manner, the pD2 value being 6.83 ± 0.20. These data clearly demonstrate that KUL-7211 selectively stimulates both ureteral β2- and β3-adrenoceptors and potently relaxes ureteral smooth muscle. KUL-7211 may be a novel and useful medication for relieving ureteral colic and promoting stone passage in urolithiasis patients.

New Combined Approach in Metallic Ureteral Stenting to Avoid Urothelial Hyperplasia: Study in Swine Model

We assessed the therapeutic value of a new treatment option for ureteral strictures that may avoid urothelial hyperplasia, which is the main cause of metallic stent failure. We used 24 pigs in this study. An experimental model of ureteral stricture was induced in all animals. Obstruction was confirmed by ultrasound and retrograde ureteropyelogram 6 weeks after model creation. The pigs were then randomly allocated to 2 experimental groups. Therapy involved placement of a 6 × 30 mm metallic ureteral covered stent in the ureteral stricture in group 1 and subsequent endoureterotomy at the ureteral segments adjacent to the 2 ends of the stent in group 2. A double pigtail stent was then deployed for 3 weeks. Completion studies 6 months after therapy included retrograde ureteropyelogram, endoluminal ultrasound and ureteroscopy to assess urothelial hyperplasia formation. At the end of the study evidence of urothelial hyperplasia was seen in 50% of the pigs in group 1 and in 29% in group 2. Four and 2 cases of cranial stent migration in groups 1 and 2, respectively, were seen at 6 months. Hyperplasia and renal involvement were statistically significantly different between the groups with more damage in group 1 than in group 2. Hyperplasia was markedly reduced when ureteral peristalsis was inhibited by endoureterotomy at the area of interaction between the stent and the ureter.

Decellularized ureter for tissue-engineered small-caliber vascular graft

Previous attempts to create small-caliber vascular prostheses have been limited. The aim of this study was to generate tissue-engineered small-diameter vascular grafts using decellularized ureters (DUs). Canine ureters were decellularized using one of four different chemical agents [Triton-X 100 (Tx), deoxycholate (DCA), trypsin, or sodium dodecyl sulfate (SDS)] and the histology, residual DNA contents, and immunogenicity of the resulting DUs were compared. The mechanical properties of the DUs were evaluated in terms of water permeability, burst strength, tensile strength, and compliance. Cultured canine endothelial cells (ECs) and myofibroblasts were seeded onto DUs and evaluated histologically. Canine carotid arteries were replaced with the EC-seeded DUs (n = 4). As controls, nonseeded DUs (n = 5) and PTFE prostheses (n = 4) were also used to replace carotid arteries. The degree of decellularization and the maintenance of the matrix were best in the Tx-treated DUs. Tx-treated and DCA-treated DUs had lower remnant DNA contents and immunogenicity than the others. The burst strength of the DUs was more than 500 mmHg and the maximum tensile strength of the DUs was not different to that of native ureters. DU compliance was similar to that of native carotid artery. The cell seeding test resulted in monolayered ECs and multilayered alpha-smooth muscle actin-positive cells on the DUs. The animal implantation model showed that the EC-seeded DUs were patent for at least 6 months after the operation, whereas the nonseeded DUs and PTFE grafts become occluded within a week. These results suggest that tissue-engineered DUs may be a potential alternative conduit for bypass surgery.

Endoscopic Evidence of Autonomous Peristaltic Activity of the Distal Human Ureter

Peristalsis of the ureter is largely thought to be a myogenic process arising from pacemaker cells in the proximal regions of the collecting system and then propagating distally.1 “Atypical” smooth muscle cells located along the length of the renal pelvis are thought to act as the primary physiologic pacemakers for these contractions.2 “Typical” smooth muscle cells do not display such activity. The ureter itself has an ability to act as a secondary latent pacemaker to generate antiperistaltic waves in the absence of stimulation from the normoperistaltic pacemaker, as demonstrated in canine ureters.

Comparison of a New Polytetrafluoroethylene-Covered Metallic Stent to a Noncovered Stent in Canine Ureters

The aim of this study was to determine the feasibility of using a newly designed polytetrafluoroethylene (PTFE)-covered metallic stent in the ureter by comparing its effectiveness with that of the noncovered stent in a canine model. We placed 14 stents in the ureters of seven mongrel dogs that weighed 30-40 kg each. The covered and noncovered stents were deployed in the right and left ureters, respectively, of six dogs. In the seventh dog, a covered stent and a double-J catheter were inserted in the right ureter, and a covered stent only was inserted in the left ureter. The first six dogs were sacrificed at 5, 10, and 15 weeks after deployment of the stents (two for each follow-up period), and the seventh dog was sacrificed at 30 weeks. There was no migration or poor expansion of any of the stents observed on plain radiography. On intravenous pyelogram and retrograde pyelogram, all of the covered stents at each follow-up period had patent lumens at the stented segments without hydronephrosis, and the passage of contrast material through it was well preserved. The noncovered stents in the dogs sacrificed at 5 and 10 weeks and one of the two dogs sacrificed at 15 weeks showed near-complete occlusion of the stent lumen due to ingrowth of the soft tissue, and severe hydronephrosis was also noted. The noncovered stent in the other dog sacrificed at 15 weeks showed the passage of contrast material without hydronephrosis, but the lumen of the stent was still nearly occluded by the soft tissue. There was no evidence of hydronephrosis or passage disturbance of the contrast material in both ureters of the dog sacrificed at 30 weeks. We conclude that the newly designed PTFE-covered stent effectively prevented the luminal occlusion caused by urothelial hyperplasia compared to the near-total occlusion of the noncovered stents, and no migration of the covered stents was noted.

Evaluation of Compliance and Stiffness of Decellularized Tissues as Scaffolds for Tissue-Engineered Small Caliber Vascular Grafts Using Intravascular Ultrasound

This study evaluated the compliance and stiffness of decellularized canine common carotid artery as well as decellularized canine ureter and compared it with that of polytetrafluoroethylene, elastin gel combined with polylactic acid tube, and canine common carotid artery. To calculate the compliance and stiffness, internal diameters and cross-sectional areas were measured according to changes in the intraluminal pressures using intravascular ultrasound in a closed circuit system equipped with a syringe pump. The pressure-area curve, stiffness parameter beta, and diameter compliance were evaluated. Canine common carotid artery and decellularized canine common carotid artery, as well as decellularized canine ureter, showed a compliant response, a J-shaped curve. However, the latter evidenced different characteristics in the low pressure range. Although the cross-sectional area of the elastin gel combined with polylactic acid tube showed some changes, it did not present a J-shape curve. Polytetrafluoroethylene exhibited a noncompliant response.The results in this study have shown that the compliance in the decellularized matrices was maintained after cell extraction, which demonstrated the importance of the remaining matrix structure in the mechanical properties of decellularized tissue. A clear difference between the decellularized matrices and synthetic materials was noted in terms of the compliance, even in materials composed of relatively elastic materials.

Constructing a Tissue-Engineered Ureter Using a Decellularized Matrix with Cultured Uroepithelial Cells and Bone Marrow-Derived Mononuclear Cells

This study investigated the efficacy of the ureteral decellularized matrix (UDM) as a scaffold material for a tissue-engineered ureter, and the effect of bone marrow-derived mononuclear cells (BM-MNC) on the neovascularization of the scaffold. Canine ureters were treated with deoxycholic acid to remove all cells. Uroepithelial cells (UEC) were obtained from canine bladders, cultured, and then seeded onto the inner surface of the UDM before transplantation into the subcutaneous space of nude mice or the omentum of nude rats. The cultured UECs began showing vacuolar degeneration 3 days after transplantation and gradually disappeared thereafter. To facilitate neovascularization in the implant, BM-MNCs were seeded around the UDM before transplantation. This facilitated the survival of the UECs, which formed three to five cellular layers after 14 days. The mean microvessel density was significantly increased in tissues seeded with BM-MNCs. However, cell-tracking experiments revealed that the increased number of capillaries in the experimental group was not due to the direct differentiation of transplanted endothelial progenitor cells. Our results demonstrate that the UDM is a useful scaffold for a tissue-engineered ureter, especially when seeded with BM-MNCs to enhance angiogenesis.

The action of glucagon and commonly used antispasmodics and analgesics on the canine ureter.

Ureteric peristalsis has been studied using extraluminal bipolar electrodes and metal foil strain gauges in both the unanaesthetized and anaesthetized dog. Electrical activity of the ureter was characterized by bipolar action potentials, which always preceded mechanical activity. In the acute studies glucagon 44 micrograms/kg i.v. was given during the unstimulated phase and again during a forced diuresis. Complete inhibition of ureteric activity was seen for 19 . 50 (+/- 3 . 76 s.e.) and 16 . 25 (+/- 1 . 59 s.e.) min respectively. During this period there was no change in the rate of urine flow. In the conscious dog glucagon was given as a bolus of 22 micrograms/kg followed by an infusion for 45 min. An infusion of 88 micrograms/kg h produced complete inhibition for 39 . 2 (+/- 2 . 41 s.e.) min. Propantheline, hyoscine, morphine, pethidine and buprenorphine were given in equivalent therapeutic human doses, but no consistent effect on ureteric peristalsis was seen. Glucagon may have a role to play in the management of ureteric colic.

The potency of KUL-7211, a selective ureteral relaxant, in isolated canine ureter: comparison with various spasmolytics

We compared the potency of a selective ureteral relaxant KUL-7211 (beta(2)/beta(3)-adrenoceptor agonist; (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid) with those of various spasmolytics on contractions in isolated canine ureteral preparations. Drug effects were evaluated on the tonic contraction induced by KCl (80 mM) and on spontaneous, 1x10(-5) M phenylephrine-, and 1x10(-6) M PGF(2alpha)-induced rhythmic contractions in isolated canine ureteral preparations using a functional experimental technique. The potencies (pD(2) value) of the following drugs were compared: KUL-7211, tamsulosin (an alpha(1A/1D)-adrenoceptor antagonist), prazosin (an alpha(1)-adrenoceptor antagonist), verapamil (a Ca(2+)-channel blocker), butylscopolamine (a nonselective muscarinic antagonist), and papaverine (a phosphodiesterase inhibitor). The rank order of relaxing potencies against KCl-induced tonic contraction was KUL-7211 (6.60)>tamsulosin(5.90)>verapamil(5.70)>papaverine(4.88)>prazosin (4.54). The rank order of potencies for reductions in spontaneous rhythmic contractions was KUL-7211 (6.80)>verapamil(6.12)>papaverine(5.05). Conversely, high concentrations of the two alpha-adrenoceptor antagonists (tamsulosin and prazosin) and of butylscopolamine enhanced the spontaneous contractions, although at low concentrations (up to 1x10(-6) M) they had no significant effects. For suppression of spasmogen-induced rhythmic contractions, the rank order of potencies was, against phenylephrine-induced contractions: KUL-7211 (6.95)>tamsulosin(6.26)>prazosin(5.68)>verapamil(5.64)>papaverine (5.03), and against PGF(2alpha)-induced contractions: KUL-7211 (7.05)>verapamil(6.70)>papaverine (5.27). Our results suggest that in dogs, the beta(2)/beta(3)-adrenoceptor agonist KUL-7211 is the most efficacious ureteral relaxant among the spasmolytics tested against various contractions. Possibly, KUL-7211 might be useful for promoting stone passage and relieving ureteral colic in urolithiasis patients.

CANINE URETERAL REPLACEMENT WITH LONG ACELLULAR MATRIX TUBE: IS IT CLINICALLY APPLICABLE?

We evaluated the effectiveness of acellular matrix used as a tube for replacement of a relatively long segment of the canine ureter. Acellular matrix was obtained by excision of the whole ureter of donor dogs that were sacrificed and not included in the study group. Retrieved ureters were treated to have complete cell lysis, while maintaining the fiber framework. The study included 10 mongrel dogs in which a 3 cm segment was excised from 1 ureter and replaced by a tube of acellular matrix of the same length and width. The new tube was sutured proximal and distal by watertight interrupted sutures around a 5Fr Double-J stent (Medical Engineering Corp., New York, New York) that remained for 6 weeks. Excretory urography was done 1 and 2 weeks after stent removal and the dogs were then sacrificed. Before sacrifice the ureter was exposed and carefully examined, and the whole specimen was excised for histopathological examination. All dogs survived surgery except 1, which died 1 week postoperatively of a malpositioned stent and urinary ascites. There was no clinically apparent postoperative complications during the presence or after the removal of the ureteral stents. One week after stent removal excretory urography showed ipsilateral mild to moderate hydroureteronephrosis in 3 dogs and no dye excretion in 6 with a normal contralateral kidney. One week later no dye excretion was detected in all except 1 dog, which showed more radiological deterioration. At the time of sacrifice there was moderate to marked hydroureteronephrosis above the level of the new tube in all dogs. Although the graft was intact in all subjects, marked shrinkage was observed. On ureteral calibration there was significant narrowing of the lumen up to complete occlusion. At 8 weeks histopathological examination showed extensive fibrosis. An acellular matrix tube is not able to replace a 3 cm segment of the canine ureter.

Comparison between CL-316243- and CGP-12177A-Induced Relaxations in Isolated Canine Ureter

We compared the effects of CL-316243, a selective β₃-adrenoceptor agonist, and CGP-12177A, a nonconventional partial β-adrenoceptor agonist, on the KCl-induced contraction in the isolated canine ureter. CL-316243 concentration dependently relaxed the ureteral contraction, the pD₂ value being 7.75 ± 0.11. This relaxation was competitively antagonized by the selective β₃-adrenoceptor antagonist SR58894A and by the nonselective β-adrenoceptor antagonist bupranolol, their pA₂ values being 7.08 ± 0.08 and 6.43 ± 0.09, respectively. CGP-12177A concentration dependently reduced the KCl-induced contraction, the pD₂ value being 6.30 ± 0.25. Even at 1 × 10^–5 mol/l, CGP-20712A (a selective β₁- adrenoceptor antagonist) did not shift the concentration-response curves for CL-316243 or CGP-12177A. SR58894A did not induce a parallel rightward shift in the concentration-response curve for CGP-12177A, but bupranolol did produce such a shift, pA₂ and slope values in the Schild plot being 7.15 ± 0.77 and 0.60 ± 0.15, respectively. Hence, the competition characteristics for SR58894A and bupranolol differed between the CL- 316243-induced and CGP-12177A-induced relaxations. Our results suggest that CGP-12177A produces ureteral relaxation in the dog via an atypical β-adrenoceptor (possibly, an atypical site/state of the β₃-adrenoceptor) as well as via the typical β₃-adrenoceptor.

Functional muscarinic cholinoceptors in the isolated canine ureter.

The purpose of present study was to characterize the functional muscarinic cholinoceptor (mAChR) subtypes in the isolated canine ureter. Carbachol (CCh), a non-selective mAChR agonist, concentration-dependently increased the frequency of the rhythmic contractions in isolated spiral ureteral preparations, the pD(2) value being 5.78+/-0.12. We then evaluated the effects of subtype-selective mAChR antagonists on the CCh-induced rhythmic contractions. The rank order of antagonistic potencies (apparent pA(2)) was 4-diphenylacetoxy- N-methylpiperidinemethiodide (4-DAMP; M3-subtype selective; 9.31+/-0.06) >atropine (non-selective; 9.16+/-0.10) >himbacine (M4-subtype selective; 7.32+/-0.18) >pirenzepine (M1-subtype selective; 6.78+/-0.16) >methoctramine (M2-subtype selective; 5.51+/-0.43). In sharp contrast, CCh concentration-dependently reduced the 80 mM KCl-induced contraction in longitudinal ureteral preparations, the pD(2) value being 4.83+/-0.10. On this CCh-induced ureteral relaxation, the rank order of antagonistic potencies (apparent pA(2)) was atropine (8.56+/-0.09) >4-DAMP (7.63+/-0.21) >himbacine (7.46+/-0.09) >methoctramine (6.54+/-0.18) >pirenzepine (6.33+/-0.22). The nitric-oxide-synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG; 1 x 10(-4) M) had no effect on the CCh-induced ureteral relaxation. These data suggest that the CCh-induced rhythmic contraction in the spiral preparation was mediated via the M3-receptor, while the CCh-induced relaxation in the longitudinal preparation was probably mediated mainly via the M4-receptor.

An experimental study of self-expanding ureteric metallic stents: macroscopic and microscopic changes in the canine ureter.

To evaluate the efficacy and safety of self-expanding metallic stents after insertion into the canine ureter. Actively expanding metallic (Nitinol) stents (diameter 8-10 mm, length 4-6 cm) were placed in eight mongrel dogs (18-34 kg). Under general anaesthesia, a midline abdominal incision was made and a stent inserted directly into the ureter through a small incision; each animal was stented on one side. The dogs were assessed after 6 or 19 days or 2, 5 (two), 6 (two) and 7 months. Ureteric specimens were evaluated both macroscopically and microscopically. Macroscopically there was no leakage of urine in any of the animals. On day 6 the inserted stent was patent despite blood clots in the mesh. The lumen was smooth and shiny in three dogs examined at 5, 6 and 7 months. One of the two dogs assessed at both 5 and 6 months had hydronephrosis associated with papillary hyper-epithelialization inside the stent, while the other animals had no dilatation of the renal pelvis. Microscopically there was loss of epithelium and bleeding of the ureteric wall at 6 days. Epithelial regeneration started after 19 days and was complete in the lumen at 2 months, with the stent incorporated into the wall of the ureter. Epithelialization was maintained up to 7 months, after which the problem of urothelial hyperplasia persisted, but an adequate lumen was maintained by epithelial regeneration. This epithelium was smooth and shiny, and composed of thin layers of cells. Self-expanding metallic stents may be effective if hyperplastic epithelialization does not occur, as the stent was epithelialized within 2 months and the regenerated epithelium maintained for up to 7 months. Metallic stents may be useful for treating patients with renal failure caused by ureteric stenosis from malignant tumours.

RABBIT MUSCLE AND URETHRAL IN SITU BIOCOMPATIBILITY PROPERTIES OF THE SELF-REINFORCED L-LACTIDE-GLYCOLIC ACID COPOLYMER 80: 20 SPIRAL STENT

A new type of self-reinforced L-lactide-glycolic acid copolymer, molar ratio 80:20, stent was developed. We evaluated the tissue biocompatibility properties of the new material. Rods made of self-reinforced L-lactide-glycolic acid copolymer were inserted into rabbit dorsal muscles and rods of latex or polyvinylchloride and silicone served as positive and negative controls, respectively. Urethral stents of self-reinforced L-lactide-glycolic acid copolymer and steel were inserted in situ via cystoscopy into the rabbit prostatic urethra. The animals were sacrificed after 2 weeks, 1, 2 and 3 months, respectively. In situ histological analysis was done. Tissue reactions around the implantation types were analyzed histologically and scored semiquantitatively. In addition, macroscopic analysis was done of the urethral in situ stents. In rabbit muscle implantation test tissue reaction to the self-reinforced L-lactide-glycolic acid copolymer stent resembled that of negative control silicone. Less than moderate chronic inflammatory changes gradually subsided after 2 weeks. Foreign materials in the tissue and the reaction to these materials began to disappear after 1 month and at 3 months were completely absent. All rabbits fitted with the stent voided normally postoperatively. Self-reinforced L-lactide-glycolic acid copolymer stents were soft, partially fragmented and easily disintegrated when touched at 2 months, and were almost completely degraded at 3 months. The material did not encroach into the urethral wall macroscopically or microscopically. No calcification on the self-reinforced L-lactide-glycolic acid copolymer stents or bladder stone formation was seen. The new self-reinforced L-lactide-glycolic acid copolymer 80:20 material is safe, highly biocompatible and suited for future clinical use. It is most appropriate for preventing postoperative urinary retention after most minimally invasive thermal treatments for benign prostatic hyperplasia.

Modification of ureteral motility and promotion of urine flow around an intraureteral obstruction by CL‐316243, phenylephrine, and furosemide in dogs

The aim of this study was to evaluate the effects of a beta3-adrenoceptor (AR) agonist (CL-316243), an alpha1-AR agonist (phenylephrine), and a loop diuretic (furosemide) on the spontaneous rhythmic contractions of the isolated canine ureter and on an acute ureteral obstruction produced by inflation of a balloon catheter in anesthetized dogs. In the isolated ureter, CL-316243 concentration dependently reduced both the amplitude and frequency of the rhythmic contractions (pD(2): 7.19 +/- 0.33), whereas phenylephrine significantly enhanced both variables (pD(2): 5.26 +/- 0.09) and furosemide reduced them only slightly. In the acute ureteral obstruction model, the intraureteral pressure (IUP) gradually rose to reach a plateau of 58.9 mm Hg after inflation of a balloon catheter within the lower ureter. Intravenous administration of CL-316243 (0.3 microg/kg) significantly reduced the elevated IUP and the resumed urine flow (UF), leading to a sustained reduction in the IUP. In contrast, the IUP continued to increase above the plateau level for 10 minutes after phenylephrine administration (10 microg/kg) and for 30 minutes after furosemide administration (1,000 microg/kg). In the phenylephrine group, the UF resumed when the IUP reached 75.8 mm Hg, and thereafter the IUP gradually decreased in parallel with the increase in the UF. From these results, we conclude that in dogs, CL-316243 reduces the IUP by allowing the UF to resume as a result of a relaxation of ureter at the obstruction site, whereas with phenylephrine, the reduction in the IUP is secondary to a resumption in the UF resulting from an induced contraction of ureter that causes an increase in hydrostatic pressure above the obstruction site.

SELF-EXPANDING NlTlNOL STENTS FOR URETER; EXPERIMENTAL STUDY

The use of stents to maintain the lumen is widelyspread in many fields including coronary artery, bronchus, biliary tract and esophagus. The aim of this study was to evaluate the efficacy and safety of self-expanding stents in the canine ureter. Actively expanding nitinol Accuflex stents (diameter 8–10 mm, length 4–6 cm, Boston Scientific Corp., MA, USA) were used for this experiment. Under general anesthesia, through a midline-abdominal incision, stents were inserted directly into the ureter through a small incision in 8 mongrel dogs (20–26 kg). Each animal had unilateral stent insertion. The observation period was 6, 23 days, 2, 5 (n=2), 6 (n=2) and 7 months. The specimens were evaluated macroscopically and microscopically. Macroscopically, all stents were patent. No urine leakage was observed in any of the animals. One dog at 5 months and another at 6 months had hydronephritis with hyperepithelialization inside the stent, while all others had no dilatation of the renal pelvis. On day 6, the inserted stent was widely patent with clots in the mesh. A smooth shiny lumen was obtained in one dog at 5 months and another at 6 months. Microscopically, at 6 days, denuded epithelium and bleeding in the ureteral wall were observed. At 5 months, epithelialization of the lumen was complete and the inserted stent was incorporated in the wall. It was concluded that self-expanding nitinol stents can be used for ureteral stenosis.

BLADDER WELDING IN RATS USING CONTROLLED TEMPERATURE CO 2 LASER SYSTEM

Laser tissue welding has potential advantages over conventional suture closure of surgical wounds. It is a noncontact technique that introduces no foreign body and limits the possibility of infections and complications. The closure could be immediately watertight and the procedure may be less traumatic, faster and easier. In spite of these positives laser welding has not yet been approved for wide use. The problem in the clinical implementation of this technique arises from the difficulty in defining the conditions under which a highly reliable weld is formed. We have assumed that the successful welding of tissues depends on the ability to monitor and control the surface temperature during the procedure, thereby avoiding underheating or overheating. The purpose of this work was to develop a laser system for reliable welding of urinary tract tissues under good temperature control. We have developed a "smart" laser system that is capable of a dual role: transmitting CO2 laser power for tissue heating, and noncontact (radiometric) temperature monitoring and control. Bladder opening (cystotomy) was performed in 38 rats. Thirty-three animals underwent laser welding. In 5 rats (control group) the bladder wound was closed with one layer of continuous 6-0 dexon sutures. Reliable welding was obtained when the surface temperature was kept at 71 + 5C. Quality of weld was controlled immediately after operation. The rats were sacrificed on days 2, 10 and 30 for histological study. Bladder closure using the laser welding system was successful in 31/33 (94%) animals. Histological examination revealed an excellent welding and healing of the tissue. Efficiency of laser welding of urinary bladder in rats was confirmed by high survival rate and quality of scar that was demonstrated by clinical and histological examinations. In the future, optimal laser welding conditions will be studied in larger animals, using CO2 lasers and other lasers, with deeper radiation penetration into tissues.

Effects of Volume Irradiated on the Function of the Canine Ureter

This study was designed to investigate the influence of the volume irradiated on the probability of ureteral complications and to provide data for volume modeling. One hundred thirty-four purpose-bred beagle dogs received single intraoperative doses of 6 MeV electrons ranging from 12 to 54 Gy to three lengths of ureter: 2, 4 or 8 cm. The response was evaluated by excretory urography. The ED50 was 21.9 Gy (95% CI 13.3-30 Gy) for 8 cm 3 years after treatment. The estimated ED50's were greater than 43 Gy for 4 cm and 85 Gy for 2 cm. Reducing the length of ureter irradiated from 8 cm to 4 cm increased the ED50 for ureteral dilation by at least a factor of 2, while reduction from 8 cm to 2 cm increased the ED50 by at least a factor of 4. The ED50 for renal injury secondary to stenosis was 30.5 Gy (95% CI 17.2-232 Gy) when an 8-cm field was irradiated. There was a significant effect of volume irradiated on the frequency of ureteral stenosis. Reducing the length of ureter included in the treatment field should allow delivery of higher doses to tumors without increased complications.

β-Adrenoceptor subtypes in the ureteral smooth muscle of rats, rabbits and dogs

We investigated the β-adrenoceptor subtypes mediating ureteral relaxation in rats, rabbits and dogs. The relaxing effects of β-adrenoceptor agonists were evaluated on KCl-induced ureteral contractions. The rank order of potency of the catecholamines tested was isoprenaline>noradrenaline>adrenaline in rat ureter; isoprenaline>adrenaline>noradrenaline in rabbit ureter; only isoprenaline was effective in canine tissues. The β 1-adrenoceptor agonist, dobutamine, produced relaxation of rat ureter. The β 2-adrenoceptor agonist, procaterol, produced more significant relaxation of rabbit ureter than did dobutamine. CL-316243 [( R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-benzodioxole-2,2-dicarboxylate] and CGP-12177A [(±)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2 H-benzimidazol-2-one hydrochloride], β 3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol. Isoprenaline-induced relaxation was antagonized by a β 1-adrenoceptor antagonist, CGP-20712A [2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1 H-imidazole-2-yl)phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate], in rats and by a β 2-adrenoceptor antagonist, ICI-118,551 [(±)-1-[(2,3-dihydro-7-methyl-1 H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], in rabbits. The non-selective β-adrenoceptor antagonist, bupranolol, antagonized isoprenaline-induced relaxation in all species tested. In conclusion, β-adrenoceptor agonists may relax ureter by stimulating mainly β 1-adrenoceptors in rats, β 2-adrenoceptors in rabbits and mainly β 3-adrenoceptors in dogs.

Characterization of histamine receptors in the ureter of the dog

We investigated the effects of histamine on the motility of isolated segments from canine ureters and characterized pharmacologically the histamine receptors involved. We also evaluated the effects of various autacoids (5-HT, carbachol, noradrenaline, thromboxane, prostaglandin F 2α) on the motility of canine ureters. Histamine as well as the H 1 receptor agonist 2-(2-pyridyl)ethylamine elicited a concentration-dependent contraction. This contractile response was antagonized by dimethindene, causing a rightward shift (pA 2 8.30) and a reduction of the slope and the maximal effect (pD′ 2 6.01) of the concentration-response curve. The histamine H 2 receptor antagonist cimetidine in a concentration of 10 −5 mol/l was ineffective concerning the concentration-response curve for histamine. After precontraction of the ureter segments (5-HT, carbachol, prostaglandin F 2α), a concentration-dependent relaxant effect was evaluated in the presence of histamine or the histamine H 2 receptor agonist impromidine. The histamine H 2 receptor antagonist cimetidine attenuated the relaxant response, causing a rightward shift of the concentration-response curve. All autacoids except thromboxane were capable of increasing contractility in canine ureters. Comparing the absolute contractile force in the presence of prostaglandin F 2α. 5-HT, carbachol, noradrenaline and potassium, we found that histamine exhibits the most marked effect on this parameter in the canine ureter. It is concluded that there are two types of histamine receptors modulating contractile activity in the canine ureter: histamine H 1 receptors, which mediate contraction, and histamine H 2 receptors, which mediate relaxation (in the precontracted tissue).