Effect of partial outlet obstruction on contractility: comparison between severe and mild obstruction

Abstract

Detrusor dysfunction is one of the most common problems in patients with outflow obstruction secondary to benign prostatic hyperplasia. These patients complain of various symptoms, including urinary frequency, urge incontinence, difficulty in voiding, and retention. The severity of the symptoms is dependent on the stage of disease and/or severity of the obstruction. We compared the changes in the rat detrusor function following both mild and severe models of partial outlet obstruction in the rat. Outflow obstructions were created by ligation of the urethra over which a catheter was placed. The size of the catheter determined whether the severity of obstruction was mild or severe (1.70 mm for mild obstruction and 1.09 mm for severe obstruction). Changes in the bladder weight, length-tension relationships, and the contractile response to field stimulation, pharmacologic agonists, and KCl were studied in bladders isolated from 1 and 2 week obstructed rats. Bladder weights of all obstructed rats increased significantly. The weight of the severe obstructed rats were significantly greater than rats subjected to mild obstruction. In general, passive length-tension curves of obstructed rats were shifted to right. The magnitude of the active tension induced by high KCl was higher in the mild obstruction and lower in the severe obstruction. The maximum response to KCl of mild obstruction was generated at greater lengths than for the other groups. In general, the contractile responses of the mild obstructed bladder body to field stimulation, bethanechol, KCl, and ATP, and of the bladder base to field stimulation, KCl, and methoxamine, were significantly increased when compared to the responses of the control bladder body and base. However in the severe obstructed bladder, the responses to field stimulation, KCl, ATP, and methoxamine were significantly reduced from the responses of the control strips; the response to bethanechol was similar for control and the severe obstructed groups. In conclusion, the severity of outlet obstruction significantly altered the contractile response of the bladder. Mild obstruction induced a mild increase in bladder mass, which was associated with significant increases to all forms of stimulation. Severe outflow obstruction induced a substantial increase in bladder mass and a significantly greater reduction in the response to field stimulation than the response to bethanechol (which was unchanged).