A standardized model for in vivo investigations of anticholinergic effectson bladder function, salivation and electromyographic characteristics of the detrusor

Purpose: The objective was to investigate the influence of two anticholiner gics, propiverine and tolterodine, on bladder contraction in a standardized in vivo model taking neurogenic innervation into account. In addition, sta ndardized salivary flow measurements enabled the evaluation of hyposalivati on, the most predominant anticholinergic side effect. Furthermore, the detr usor electromyogram (EMG) was evaluated. Materials and Methods: 10 male mini pigs were anaesthesized. The carotic ar tery was cannulated for blood pressure control and the jugular vein for adm inistration of propiverine 0.4 mg/kg b.w. and L(+) tolterodine 0.06 mg/kg b .w. For stimulation-induced salivary flow measurements, both lingual nerves were exposed and a cuff electrode placed around the nerves. After exposure of the bladder, 2 electrodes were implanted under the serosa of the bladde r dome to record the detrusor EMG and a cystostomy was performed to assess cystometrographic measurements. A bilateral ureterocutaneostomy was perform ed in order to maintain a constant bladder volume during the trial. The ure thra was then ligated to initiate isovolumetric bladder contraction during sacral anterior root stimulation (SARS). Results: In all experiments, reproducible intravesical pressure values (pve s) and salivary flow rates were elicited for each animal during electrostim ulation before administration of the drug. Bladder pressure: After administ ration of propiverine, the neurostimulation-induced rise in pves dropped to 64% of the initial value. After administration of tolterodine, pves declin ed to 60%. Salivation: After propiverine, salivary flow dropped to 61%. inh ibition of salivary flow under tolterodine was about 56%. Similar results w ere obtained in detrusor EMG recordings. Both propiverine and tolterodine i ncreased the heart rate temporarily by a median of 18%. No change in ECG re cordings was noted after administration of the test substances. Conclusions: The in vivo model presented herein allows comparative studies of pharmacological effects on bladder function. Both drugs have similar eff ects on bladder inhibition in mini pigs. Hyposalivation was comparable in b oth drugs.