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You are here: Home / Publications / Bibliographies and Resource Guides / Canine Models in Biomedical Research, 1990-2009  / Urinary System  Printer Friendly Page
Canine Models in Biomedical Research,  1990-2009
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Urinary System

Carvalho, M., J.P. Lulich, C.A. Osborne, and Y. Nakagawa (2003). Role of urinary inhibitors of crystallization in uric acid nephrolithiasis: dalmatian dog model. Urology 62(3): 566-570. ISSN: 0090-4295.
NAL Call Number: RC870
Abstract: Objectives. To study the role of urinary inhibitors on crystallization-nephrocalcin, Tamm-Horsfall protein (THP), and glycosaminoglycans (GAGs)-in hyperuricosuric nephrolithiasis using Dalmatian dogs, a breed well-known for high levels of uric acid excretion, in an in vivo model. Methods. Urine samples were collected from 10 stone-forming Dalmatian dogs and from 5 age-matched Dalmatians without kidney stones. Purine derivatives present in urine were studied by high-performance liquid chromatography. THP, GAGs, and nephrocalcin were isolated and measured. Results. As expected, the Dalmatians excreted a large amount of uric acid in urine, but without differences between the two groups (0.42 +- 0.08 mg/mg creatinine versus 0.48 +- 0.11 mg/mg creatinine for stone-forming and healthy Dalmatians, respectively, P = 0.64). No other metabolites were derived from purine in their urine. Stone-forming Dalmatians showed significantly lower urinary excretion of THP than did normal Dalmatians (0.09 +- 0.03 mg/mg creatinine versus 0.21 +- 0.03 mg/mg creatinine, P <0.03). The urinary excretion of GAGs was lower in the stone-forming Dalmatians, although the difference was not statistically significant. Inhibition of calcium oxalate monohydrate crystal growth caused by nephrocalcin isoforms from healthy and stone-forming dogs were in the same order of apprx10-7 M, as calculated from a Langmuir isotherm type plot. Conclusions. The urinary excretion of THP and GAGs was decreased in stone-forming Dalmatians compared with healthy ones. Our results support the suitability of Dalmatian dogs as an in vivo model to investigate the interrelationship of urine inhibitors of crystallization and hyperuricosuria.
Descriptors: biochemistry and molecular biophysics, metabolism, urinary system, chemical coordination and homeostasis, nephrolithiasis, kidney calculi, urologic disease, high performance liquid chromatography, chromatographic techniques, laboratory techniques, crystallization .

Chen, D., B. Jefferson, S.J. Harvey, K. Zheng, C.J. Gartley, R.M. Jacobs, and P.S. Thorner (2003). Cyclosporine a slows the progressive renal disease of alport syndrome (x-linked hereditary nephritis): results from a canine model. Journal of the American Society of Nephrology 14(3): 690-698. ISSN: 1046-6673.
Abstract: Alport syndrome refers to a hereditary disorder characterized by progressive renal disease and a multilaminar appearance to the glomerular basement membrane (GBM). In a small group of patients with Alport syndrome, cyclosporine A was reported to decrease proteinuria and maintain stable renal function over 7 to 10 yr of follow-up. The present study examined the effect of cyclosporine A on GBM structure and the progression to renal failure in a canine model of X-linked Alport syndrome. Affected male dogs and normal male dogs treated with cyclosporine A underwent serial renal biopsies. Body weight, serum concentrations of creatinine and albumin, and GFR were sequentially determined. Controls consisted of untreated dogs that developed end-stage renal failure by 8 mo of age. Renal biopsies were assessed for glomerulosclerosis and the percent of multilaminar GBM as measured by image analysis. Significant differences were found between treated and untreated affected dogs for weight, serum creatinine, and GFR. There was a significant delay in the progression of multilaminar change to the GBM, although treated affected dogs at termination had attained approximately 100% split GBM as did untreated affected dogs. A significant difference in the number of sclerotic glomeruli was also noted; treated dogs rarely developed obsolete glomeruli during the period studied. Interstitial fibrosis was not significantly affected by cyclosporine A treatment. These findings indicate that cyclosporine A is beneficial in slowing, but not stopping, the clinical and pathologic progression of Alport syndrome. At least part of this beneficial effect comes from a delayed deterioration of GBM structure, which in turn may be related to glomerular hemodynamics altered by cyclosporine A.
Descriptors: genetics, pharmacology, urinary system, chemical coordination and homeostasis, Alport syndrome, X linked hereditary nephritis, congenital disease, genetic disease, urologic disease, glomerulosclerosis, interstitial fibrosis, disease miscellaneous, renal disease, drug therapy, renal failure, image analysis, imaging and microscopy techniques, laboratory techniques, renal biopsy, glomerular filtration rate, body weight, glomerular hemodynamics.

Choi, E.W. and C.W. Lee (2004). Development of canine nephrotic syndrome model. Journal of Veterinary Medical Science 66(2): 169-174. ISSN: 0916-7250.
NAL Call Number: SF604.J342
Abstract: To develop an experimental animal model for immune-mediated glomerulonephritis and nephrotic syndrome, nine healthy dogs were sensitized by intravenous injection with 1 mug of endotoxin and 5 mg of native bovine serum albumin. After 1 week, 120 mg of cationized bovine serum albumin was injected intravenously 5 times a week. Among nine dogs, five dogs were confirmed as having developed glomerulonephritis and nephrotic syndrome by increase of urine protein-to-creatinine ratio (>1.0), hypoalbuminemia (<1.5 g/dl), hypercholesterolemia (>240 mg/dl), and edema. This model should be useful for studying immune-mediated glomerulonephritis and nephrotic syndrome.
Descriptors: immune system, chemical coordination and homeostasis, urinary system, veterinary medicine, medical sciences, glomerulonephritis, immune system disease, urologic disease, nephrotic syndrome, animal model development, urinary protein to creatinine ratio.

Fryer, R.M., L. Preusser, S. Calzadilla, Y. Hu, H. Xu, K. Marsh, B. Cox, C.T. Lin, M. Gopalakrishnan, and G. Reinhart (2004). A-278637, a novel atp-sensitive potassium channel opener: hemodynamic comparison to zd-6169, way-133537 and nifedipine in the anesthetized canine. FASEB Journal 18(4-5): Abst. 404.3. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: cardiovascular system, transport and circulation, pharmacology, urinary system, chemical coordination and homeostasis, overactive bladder, urinary incontinence, urologic disease, therapy .

Halpenny, M., F. Markos, H.M. Snow, P.F. Duggan, E. Gaffney, D.P. O'Connell, and G.D. Shorten (2001). Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs. Critical Care Medicine. 29(4): 855-860. ISSN: 0090-3493.
Abstract: OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.
Descriptors: animal model, female, beagle dogs, hypovolemia, fenoldopam, blood flow, glomerular filtration rate, natriuresis.

Hoag, J.B., M. Liu, R.B. Easley, M.F. Britos Bray, P. Kesari, H. Hassoun, M. Haas, R.M. Tuder, H. Rabb, and B.A. Simon (2008). Effects of acid aspiration-induced acute lung injury on kidney function. American Journal of Physiology. Renal Physiology 294(4): F900-8. ISSN: 0363-6127.
Abstract: Acute lung injury (ALI) in combination with acute kidney injury carries a mortality approaching 80% in the intensive care unit. Recently, attention has focused on the interaction of the lung and kidney in the setting of ALI and mechanical ventilation (MV). Small animal models of ALI and MV have demonstrated changes in inflammatory mediators, water channels, apoptosis, and function in the kidney early in the course of injury. The purpose of this investigation was to test the hypothesis that ALI and injurious MV cause early, measurable changes in kidney structure and function in a canine HCl aspiration model of ALI when hemodynamics and arterial blood gas tensions are carefully controlled. Intratracheal HCl induced profound ALI as demonstrated by increased shunt fraction and airway pressures compared with sham injury. Sham-injured animals had similar mean arterial pressure and arterial Pco(2) and HCO(3) levels compared with injured animals. Measurements of renal function including renal blood flow, urine flow, serum creatinine, glomerular filtration rate, urine albumin-to-creatinine ratio, and kidney histology scores were not different between groups. With maintenance of hemodynamic parameters and alveolar ventilation, ALI and injurious MV do not alter kidney structure and function early in the course of injury in this acid aspiration canine model. Kidney injury in large animal models may be more similar to humans and may differ from results seen in small animal models.
Descriptors: hydrochloric acid toxicity, kidney function tests, lung diseases etiology, lung injury, administration, inhalation, blood pressure drug effects, carbon dioxide blood, cardiac output drug effects, creatinine blood, diuresis drug effects, dogs, glomerular filtration rate drug effects, hydrochloric acid administration and dosage, hydrogen ion concentration, lung drug effects, lung pathology, models, animal, pulmonary alveoli drug effects, pulmonary alveoli pathology.

Janssens, L.A.A. and S. Peeters (1997). Comparisons between stress incontinence in women and sphincter mechanisms incompetence in the female dog. Veterinary Record 141(24): 620-625. ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: comparisons, women, urinary incontinence, sphincters, bladder, urethra, stresses, physiopathology, treatment.

Kaewsakhorn, T., M. Gower, W. Kisseberth, C. Capen, M. Calverley, and N. Inpanbutr (2004). Effects of calcitriol and medium chain triglyceride (mct) on cell growth of the canine transitional cell carcinoma of the urinary bladder (tcc) in vitro. FASEB Journal 18(4-5): Abst. 68.8. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: calcitriol , cell biology, cell proliferation, pharmacology, tumor biology, bladder transitional cell carcinoma, neoplastic disease, urologic disease, therapy, western blot, genetic techniques, laboratory techniques, drug regimen.

Konety, B.-R., T.-S. Griffith, S.-J. Sirintrapun, J.-M. Rippentrop, A.-H. Stolpen, B.-R. De-Young, T.-L. Ratliff, and R.-D. Williams (2003). Effect of intra-prostatic injection of adenovirus-trail in vivo in the dog prostate. Journal of Urology 169(4 Supplement): 212. ISSN: 0022-5347.
NAL Call Number: 448.8 J8234
Descriptors: methods and techniques, molecular genetics, biochemistry and molecular biophysics, reproductive system, reproduction , h and e staining, hematoxylin eosin staining, histology and cytology techniques, laboratory techniques, intra prostatic injection, clinical techniques, pelvic computed tomography, imaging and microscopy techniques, radical prostatectomy, therapeutic and prophylactic techniques, periprostatic inflammation.

Marcovich, R., A.L. Williams, B.D. Seifman, and J.S.J. Wolf (2000). Development of a canine model to assess the biochemical stress response to laparoscopic and open surgery. Journal of Endourology 14(Supplement 1): A3. ISSN: 0892-7790.
Descriptors: urinary system, chemical coordination and homeostasis, methods and techniques, pneumoperitoneum, laparoscopic nephrectomy, open nephrectomy, biochemical stress response, surgical stress response, meeting abstract

Nanri, M., N. Mori, T. Kirimoto, T. Uji, and M. Kiniwa (2004). The effect of propiverine hydrochloride in a canine urinary frequency model associated with bladder hyperactivity. Journal of Pharmacological Sciences 94(Supplement 1): 265P. ISSN: 1347-8613.
Descriptors: pharmacology, urinary system, chemical coordination and homeostasis, veterinary medicine, medical sciences, bladder hyperactivity, urologic disease, lower urinary tract dysfunction, urologic disease, micturition interval

Olson, M.E. and R. Hjelm (2008). Canine bladder tissue responses to injectable stabilized non-animal hyaluronic acid/dextranomer (NASHA/Dx) gel. European Journal of Obstetrics, Gynecology, and Reproductive Biology 138(1): 114-5. ISSN: 0301-2115.
Descriptors: biocompatible materials administration and dosage, dextrans administration and dosage, foreign body migration pathology, foreign body reaction pathology, hyaluronic acid administration and dosage, urinary bladder drug effects, dogs, foreign bodies, gels, injections, microspheres, models, animal, urinary incontinence, stress drug therapy.

Pomeroy, M.J. and J.L. Robertson (2004). The relationship of age, sex, and glomerular location to the development of spontaneous lesions in the canine kidney: analysis of a life-span study. Toxicologic Pathology 32(2): 237-242. ISSN: 0192-6233.
Abstract: It is well documented that the presence of spontaneous renal disease and renal dysfunction increases with age in many species of mammals. Such alterations in renal structure and function may significantly affect the interpretation of long-term toxicology studies. The purpose of the present study was to assess the temporal evolution of selected renal lesions (cysts, interstitial inflammation, interstitial fibrosis, and glomerulosclerosis) in laboratory Beagle dogs, an important animal model in chronic toxicology studies. We examined representative sections of the kidneys from 159 purpose-bred and laboratory housed Beagle dogs and analyzed the extent and distribution of spontaneous lesions using the World Health Organization classification system for renal lesions. All dogs examined had renal lesions of varying severities. In the youngest dogs (up to 2 years of age), the density and severity of lesions were minimal, but were more severe by middle age (defined as 3-7 years). The density and severity of interstitial fibrosis and inflammation progressed with advancing age (p<0.0001 for both) in both sexes. The density of tubular cysts increased linearly with advancing age in females (p=0.0006), but not in males (p=0.49). The cortical distribution of glomeruli and advancing age of dogs were significantly related to the development of glomerulosclerosis. As age increased, the presence of glomerulosclerosis increased (p=0.0008). These data indicate that the development of renal lesions is progressive over the lifetime of a genetically similar population of laboratory Beagle dogs maintained under optimal standard environmental conditions. This information may be useful in the interpretation of compound effects during chronic toxicology studies in the dog.
Descriptors: breed, Beagle, age differences, aging, cysts pathological, fibrosis, glomerulus, inflammation, kidney diseases, lifespan, sex differences.

Salomon, C., D. Casanova, G. Solares, C. Qualls, J. Gonzalez Cotorruelo, and M. Arias (2007). Blood volume expansion with hyperoncotic colloids deteriorates allograft function in a canine model of renal transplantation. Transplantation Proceedings 39(7): 2112-4. ISSN: 0041-1345.
NAL Call Number: RD120.7.T68
Abstract: PURPOSE: We investigated the effects of acute maximal hydratation with hemoce (H) and dextran-40 (D40) on the postoperative graft function, following renal transplantation (RT) in a canine model. METHODS: After induction of anesthesia with pentobarbital (5 mg/kg), 18 beagle dogs were randomized to receive either saline solution to increase the central venous pressure (CVP) to 5 mm Hg (GI); H solution to increase the CVP to 10 mm Hg (GII); or D40 to achieve 15 mm Hg (GIII), before reperfusion. A pulmonary artery catheter was used to measure CVP, mean pulmonary artery pressure, and cardiac output (CO). The surgical procedure consisted of autotransplantation of the dog's left kidney an hour prior to cold ischemia with University of Wisconsin solution, followed by contralateral nephrectomy. Diuresis, creatinine (Cr), and BUN levels were measure at 24 hours before RT, as well as 24, 48, and 72 hours after the procedure. RESULTS: Only in the treated groups did cardiac filling pressures and CO increase as a result of hydration. Only in the GI group did serum Cr and blood urea nitrogen significantly peak at the second postoperative day while it continued to increase at two (GII) and three (GIII) times greater than GI on the third day. Histological examination showed osmotic nephrosis like-lesions only among treated grafts. CONCLUSION: We concluded that maximal hydration with H and D40 colloid deteriorated postoperative graft function after RT. We believe that in the future the effects of any colloid solution should be tested in an animal model in the fashion as we have described, in order to know which one, and at what dose, is the safest to improve kidney allograft outcome.
Descriptors: blood volume physiology, colloids therapeutic use, kidney transplantation physiology, transplantation, homologous physiology, blood pressure, blood urea nitrogen, creatinine blood, dogs, models, animal.

Shau, Y.W., S.H. Pao, N.K. Chou, K.J. Chang, and J.J. Shyu (2009). Renal vascular perfusion index in a canine model. Ultrasound in Medicine and Biology 35(1): 36-43.
NAL Call Number: QC244.U4
Abstract: Decreased renal perfusion plays an important role in the progression toward renal failure. In this study, a novel measure was proposed to quantify renal perfusion using canine model. Serial renal vascular images at different vascular areas including the whole vascular tree, interlobar, arcuate and interlobular vessels were captured. Image processing software was designed to analyze the changes of power Doppler intensity of colored pixels within regions-of-interest (ROI). For a given ROI, the power Doppler vascular index (PDVI) was found to fluctuate with the cardiac cycle. It was also noted that the power Doppler signals generated by arterial vessels have different fluctuating waveforms and different phase compared with the signal derived from venous vessels. A power Doppler correlation-map was developed to differentiate the arteries and veins in the ROI. Using the serial power Doppler images and the derived flow direction information, the interlobular perfusion can be strongly quantified. The renal vascular perfusion index (RVPI) defined as the ratio of PDVI(max) versus PDVI(min) was significantly higher in the interlobular vessel areas than three other areas for seven healthy dogs. The RVPI resembles the systolic/diastolic (S/D) ratio that commonly reflects arterial hemodynamics. RVPI and power Doppler correlation-map reveal more "dynamic" sense of vascular perfusion and provide a novel approach for the examination of renal function in clinical practice.
Descriptors: image processing, computer assisted, kidney ultrasonography, renal circulation physiology, ultrasonography, doppler, color methods, blood flow velocity, dogs, kidney function tests, models, animal, perfusion, renal artery ultrasonography, renal veins ultrasonography.

Tomiyama, Y., M. Murakami, Y. Yamazaki, M. Kojima, and M. Akahane (2003). Comparison between cl-316243- and cgp-12177a-induced relaxations in isolated canine ureter. Pharmacology 68(3): 140-146. ISSN: 0031-7012.
NAL Call Number: RM1.P473
Abstract: We compared the effects of CL-316243, a selective beta3-adrenoceptor agonist, and CGP-12177A, a nonconventional partial beta-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 beta3-adrenoceptor antagonist SR58894A and by the nonselective beta-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 X 10-5 mol/l, CGP-20712A (a selective beta1-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 beta-adrenoceptor (possibly, an atypical site/state of the beta3-adrenoceptor) as well as via the typical beta3-adrenoceptor.
Descriptors: biochemistry and molecular biophysics, pharmacology, urinary system, chemical coordination and homeostasis, concentration response curves.

Wuensch, S., M. Gekle, U. Kersting, B. Schuricht, and H. Oberleithner (1995). Phenotypically and karyotypically distinct madin-darby canine kidney cell clones respond differently to alkaline stress. Journal of Cellular Physiology 164(1): 164-171. ISSN: 0021-9541.
NAL Call Number: 444.8 J822
Abstract: We isolated two cell clones from the wild-type Madin-Darby canine kidney cell line (MDCK) that resembles renal collecting duct epithelium. Morphology and karyotypes of the two cell clones were evaluated. The MDCK-C7 cell clone morphologically resembles principal cells (polygonal cell shape, flat), while the MDCK-C11 clone resembles intercalated cells (cuboidal cell shape, high). The diploid chromosome number of MDCK-C7 cells is 83.1 +- 0.2 (n = 139); that for MDCK-C11 cells is 78.8 +- 0.1 (n = 128). Culture of MDCK-C7 cells in alkaline medium (pH 7.7) induced irreversible phenotypical and genotypical alterations. Transformed MDCK-C7F cells are characterized by two abnormal (biarmed) chromosomes. In contrast, MDCK-C11 cells are not phenotypically altered by alkaline stress. In order to elucidate the role of intracellular pH (pH-i) in the transformation process, we measured pH-i under control conditions (pH 7.4), after 5 min exposure to alkaline stress ("acute experiment," pH 7.7) and after incubation of the cells in alkaline medium for two weeks ("chronic experiment," pH 7.7). Under control conditions, MDCK-C7 cells maintained pH, at 7.14 +- 0.01 (n = 154) and MDCK-C11 cells at 7.01 +- 0.01 (n = 147). Acute alkaline stress increased pH-i of both cell types to similar steady-state values. Under chronic alkaline stress, MDCK-C7 cells were unable to maintain intracellular pH within normal limits exhibiting sustained alkalinization, whereas MDCK-C11 cells could successfully regulate pH-i. We conclude that wild-type MDCK cells consist of two genetically distinct subpopulations with different morphology and function. Only the MDCK-C7 clone that resembles the principle cell type of renal collecting duct can be transformed by alkaline stress while the MDCK-C11 clone resists this treatment, due to efficient pH-i control mechanisms.
Descriptors: cell biology, development, genetics, morphology, urinary system, chemical coordination and homeostasis, alkalinization, ph, proliferation, ultrastructure .

Wynn, V.M., E.B. Davidson, R.G. Higbee, J.W. Ritchey, T.D. Ridgway, K.E. Bartels, and M.D. Lucroy (2003). In vitro effects of pulsed holmium laser energy on canine uroliths and porcine cadaveric urethra. Lasers in Surgery and Medicine 33(4): 243-6. ISSN: 0196-8092.
Descriptors: animal model, human lithotripsy procedures, holmium laser energy, canine uroliths, porcine urethra.

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