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.
Showing the most recent 10 out of 27 publications
