Continuous bladder infusion methods for studying voiding function in the ambulatory mouse

Abstract

Objectives To develop a method for chronic cannulation of the mouse bladder that would enable repeated intravesical drug delivery and measurement of voiding patterns in unrestrained mice under controlled infusion conditions. Methods Fifteen female mice were anesthetized with halothane and implanted with a 3F polyurethane bladder catheter. The catheter exited from the back through mesh and a polysulfone button into a spring coil that protected the catheter and tethered the mouse. A counterbalanced swivel and infusion pump permitted unencumbered mobility during continuous intravesical perfusion. Results Patent catheterization was consistently achieved for at least 5 weeks. The voiding patterns produced with an infusion pump were stable not only within a study session but also during the course of several weeks. The catheters remained patent but eventually withdrew from the bladder in 9 mice, at which point the mice were killed. The mesh eventually emerged from the skin in 4 animals without evidence of infection and was associated with catheter leakage at the level of mesh exposure. The subcutaneous placement of the mesh and tether assembly adequately transferred torque to the swivel without catheter obstruction. One mouse died unexpectedly during anesthesia; another was killed 1 week after catheter implantation because of an intraperitoneal leak. No bladder stones were identified. The results of the urine cultures were inconclusive. Conclusions Continuous, patent catheterization of the murine bladder can be achieved consistently for a period of 5 weeks. When used in combination with counterbalanced swivel assemblies and electronic balance technology, these methods permit prolonged evaluation of micturition patterns in the awake, ambulatory mouse.