The objective of this project is to create a physiologically accurate and quantifiable model of obstructive uropathy in an animal species with well characterized lower urinary tract function. It is clear that obstructive uropathy can led to bladder and ureteral dysfunction which can adversely influence renal function, but little is known about the pathophysiology of the deleterious effects of obstructive uropathy. Clinicians have neither an accurate method to determine whether obstruction is present, or whether, if present, the obstruction is dangerous and requires correction. Obstructive uropathy will be created in cats by placement of a silicon sleeve around the midurethra to prevent urethral opening ('relaxation') during voiding. The degree of obstruction will be assessed by measurement of the intravesical pressure and urine flow rate over the period of weeks to months, and up to a year. Once the obstructive model is well established, and we have urodynamic, morphologic, pharmacologic and in vitro contractility data, ureteral function in relation to known levels of obstruction will be measured using dynamic renal scans and direct pressure flow ureteral perfusion - at bladder volumes or pressures known to occur in each experimental animal. Kidney function will also be assessed by various methods in animals in which obstructive vesical and ureteral dysfunction are known and has been quantitated. The observations in this regard will be correlated with morphologic studies on the kidney in the same animals. The planned multi-organ multidisciplinary correlative studies will allow us to determine the pathogenetic mechanism(s) responsible for vesical, ureteral and renal dysfunction in obstructive uropathy.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Upstate Medical University
Department
Type
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
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Levin, R M; Monson, F C; Longhurst, P A et al. (1994) Rabbit as a model of urinary bladder function. Neurourol Urodyn 13:119-35
Zhao, Y; Wein, A J; Levin, R M (1993) Role of calcium in mediating the biphasic contraction of the rabbit urinary bladder. Gen Pharmacol 24:727-31
Hess, M E; Barasha, B; Winters, S et al. (1993) Effect of thyroxine on urinary bladder autonomic receptor densities and contractility. Pharmacology 46:248-53
Samadzadeh, S; Tong, Y C; Wein, A J et al. (1992) Influence of the bathing medium on the contractile responses of the rabbit urinary bladder. Pharmacology 45:99-106
Longhurst, P A; Eika, B; Leggett, R E et al. (1992) Urinary bladder function in the tight-skin mouse. J Urol 148:1611-4
Bilgen, A; Wein, A J; Zhao, Y et al. (1992) Effects of anoxia on the biphasic response of isolated strips of rabbit bladder to field stimulation, bethanechol, methoxamine and KCl. Pharmacology 44:283-9
Levin, R M; Haugaard, N; Packard, D et al. (1992) Effect of ryanodine on mitochondrial respiration. Pharmacology 45:117-20
Tammela, T L; Wein, A J; Levin, R M (1992) Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation. J Urol 148:1937-40

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