Oh Seung-June, Paick Sung Hyun, Lim Dae Jung, Lee Eunsik, Lee Sang Eun
Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Neurourol Urodyn. 2005;24(3):288-94. doi: 10.1002/nau.20113.
We investigated the invitro effects of local anesthetics on the contractility of the human bladder.
By measuring the invitro isometric contractions of human bladder strips, we determined the effects of tetracaine, bupivacaine, lidocaine, and ropivacaine on the basal spontaneous contractions and contractions induced by various stimuli, namely, KCl (60 mM), carbachol (CCh), and electrical field stimulation (EFS). The effect of local anesthetic agents on Ca(2+)-independent sustained tonic contraction (SuTC) of the detrusor was also investigated.
Local anesthetics increased phasic and tonic spontaneous contractile activity dose dependently in the concentration range 1-500 muM, but abolished phasic activity at higher concentrations. Local anesthetic agents inhibited nerve-mediated contraction (EFS, 0.8 msec) in a concentration-dependent manner (ropivacaine > tetracaine = bupivacaine > lidocaine), and inhibited non-nerve mediated contractions induced by KCl, long pulse EFS (direct muscle stimulation, 100 msec), and CCh. Inhibitory potency on non-nerve mediated contraction was for long pulse EFS: ropivacaine = tetracaine > bupivacaine = lidocaine and for KCl- and CCh-induced contractions: ropivacaine > tetracaine > bupivacaine = lidocaine. Higher concentrations of local anesthetics were needed to inhibit non-nerve-mediated bladder contraction than nerve-mediated contraction. SuTC was suppressed by all local anesthetics concentration dependently.
Our study demonstrates that local anesthetics have inhibitory effects on the contraction of human bladder as induced by different stimulants and concentrations. Their effects and differences suggest that they may be considered potentially useful as diagnostic and therapeutic agents for bladder dysfunction.
我们研究了局部麻醉药对人膀胱收缩性的体外作用。
通过测量人膀胱条带的体外等长收缩,我们确定了丁卡因、布比卡因、利多卡因和罗哌卡因对基础自发收缩以及由各种刺激诱导的收缩的影响,这些刺激包括氯化钾(60 mM)、卡巴胆碱(CCh)和电场刺激(EFS)。还研究了局部麻醉药对逼尿肌钙(2+)非依赖性持续强直性收缩(SuTC)的影响。
在1 - 500 μM浓度范围内,局部麻醉药剂量依赖性地增加了相性和强直性自发收缩活动,但在较高浓度时消除了相性活动。局部麻醉药以浓度依赖性方式抑制神经介导的收缩(EFS,0.8毫秒)(罗哌卡因>丁卡因=布比卡因>利多卡因),并抑制由氯化钾、长脉冲EFS(直接肌肉刺激,100毫秒)和CCh诱导的非神经介导的收缩。对非神经介导收缩的抑制效力,对于长脉冲EFS:罗哌卡因=丁卡因>布比卡因=利多卡因,对于氯化钾和CCh诱导的收缩:罗哌卡因>丁卡因>布比卡因=利多卡因。抑制非神经介导的膀胱收缩比抑制神经介导的收缩需要更高浓度的局部麻醉药。所有局部麻醉药均浓度依赖性地抑制SuTC。
我们的研究表明,局部麻醉药对不同刺激物和浓度诱导的人膀胱收缩具有抑制作用。它们的作用和差异表明,它们可能被认为是用于膀胱功能障碍的潜在诊断和治疗药物。