The effect of intravesical ketoprofen on acetylcholine-evoked urinary bladder contractility and detrusor overactivity in the anesthetized rabbit model.

Abstract

Intraurethral procedures such as the transurethral resection of the prostate can generate detrusor overactivity and bladder irritability. The rabbit model of detrusor overactivity has proven to be an excellent model to study the effects of drugs on detrusor overactivity. Using this model, we evaluated the responses to intravesical ketoprofen. In this model, each rabbit is anesthetized and the right external carotid artery is cannulated for blood pressure monitoring. A catheter is inserted through the femoral artery and is used for administration of acetylcholine (Ach). The bladder is exposed and catheterized for bladder pressure monitoring and drug addition and the proximal urethra is ligated. Cystometry is performed, the bladder drained, and 20 ml buffer placed in the bladder. After 30 min Ach is injected proximal to the vesical artery and the response of the bladder and blood pressure is recorded. Ach administration is repeated at 10-min intervals until three consistent responses are obtained. The bladder is drained and 20 ml of ketoprofen (100 microM final concentration) is placed in the bladder. Ach injections are repeated as given above at 10 min intervals and observed for 4 h. At the end of the experiment, a second cystometry is performed. The following is a summary of the results: Ketoprofen had no effect on either micturition pressure or the intravesical volume at micturition. Ketoprofen administration resulted in a progressive 50% decrease in the response to Ach. Ketoprofen mediated a progressive decrease in detrusor overactivity amplitude and frequency, reaching a maximum at 120-180 min.