Administration of Drugs Using Implantable Micropump.

本文用家兔脊髓，观察了脑啡肽能或γ-氨基丁酸能活动在下尿路神经源性功能障碍中的作用。在脊髓横断急性期，离体腰骶髓脑啡肽能活动显著增加，导致膀胱活动受到强烈抑制。在患有逼尿肌括约肌协同失调（DSD）的慢性脊髓家兔中，GABA拮抗剂（印防己毒素和法克罗芬）从未影响膀胱和括约肌活动。这一发现表明，DSD进一步增强缺乏内源性GABA。通过使用植入的微泵的DSD的热内给药。在接受1 μ g/h巴氯芬的动物中，DSD已改善2周。在5 μ g/h巴克罗芬输注组中，其改善持续8至12周。进一步增加巴克罗芬剂量（10 μ g/h）可将有效期延长至12或16周。因此，在慢性脊髓兔中证实了鞘内注射巴克罗芬的良好治疗效果。然而，这项研究不能在DSD患者中进行，因为伦理问题。鞘内注射GABA激动剂极大地增加了膀胱容量，并取消了病理性膀胱收缩和横纹尿道括约肌活动在慢性脊髓兔。基于这一结果，巴氯芬用于治疗

Using spinal rabbits, the contribution of enkephalinergic or GABA-minergic activity to neurogenic dysfuction of lower urinary tract was evaluated. At acute stage of spinal cord transection, enkephalinergic activity dominantly increased at the isolated lumbosacral cord, resulting in a strong supression of bladder activity. In chronic spinal rabbits with detrusor sphincter dyssynergia (DSD), GABA antagonists (picrotoxin and phacrofen) never affected the bladder and sphincter activity. This finding would indicate that DSD is further enhanced with a lack of endogenous GABA.atment of DSD by the intrathercal administration using an implanted micropump. In animals receiving 1 mug/h baclofen, DSD had been improved for 2 weeks. In 5 mug/h bacrofen infusion group, its improvement was sustained during 8 to 12 weeks. Further increase in bacrofen dose (10 mug/h) prolonged the effective period to 12 or 16 weeks. Thus, an excellent therapeutic effect of intrathecal bacrofen infusion was confirmed in chronic spinal rabbits. However, this study could not be performed in patients with DSD because of ethical problems.The intrathecal injection of GABA agonists extremely increased bladder capacity and abolished both pathologic bladder contraction and striated urethral sphincter activity in chronic spinal rabbits. Based on this result, baclofen was used for the tre