Effect of distigmine combined with propiverine on bladder activity in rats with spinal cord injury

Abstract

It is not uncommon for patients with spinal cord injury to have both detrusor overactivity during the storage phase and detrusor underactivity during the voiding phase. However, there has been no information about the efficacy of combined treatment with cholinesterase inhibitors and anti-muscarinic agents for this condition. Therefore, the effect of co-administration of distigmine bromide (a cholinesterase inhibitor) and propiverine hydrochloride (an anti-muscarinic agent) on bladder activity was examined in rats with spinal cord injury. Rats were anesthetized with isoflurane and the lower thoracic spinal cord was transected. The bladder was emptied by abdominal compression twice a day for 14 days after surgery. A total of 4 weeks after surgery, the animals were anesthetized with urethane, and the effect of intravenous injection of distigmine (0.01-1 mg/kg) followed by propiverine (1 mg/kg) on continuous cystometry parameters was examined. After injection of distigmine (0.1 and 1 mg/kg), the maximum bladder contraction pressure was significantly increased, and the duration of bladder contraction and the interval between bladder contractions were significantly prolonged. The baseline bladder pressure was not changed by injection of distigmine. After the addition of propiverine, the interval between bladder contractions was significantly further prolonged without any change of the maximum contraction pressure, baseline pressure or duration of bladder contraction. The residual volume after voiding bladder contraction was less than 0.1 mL in all animals. In conclusion, co-administration of distigmine with propiverine might improve both bladder underactivity during the voiding phase and bladder overactivity during the storage phase.