Kim Dae Kyung, Jankowski Ron J, Pruchnic Ryan, de Miguel Fernando, Yoshimura Naoki, Honda Masashi, Furuta Akira, Chancellor Michael B
Department of Urology, Eulji University, Daejeon, Republic of Korea.
Urology. 2009 Feb;73(2):437-41. doi: 10.1016/j.urology.2008.06.019. Epub 2008 Aug 13.
Lidocaine cytotoxicity has been reported in some cell types, which could affect its use as a local anesthetic in cell-based therapy. We evaluated the in vitro and in vivo effect of lidocaine on rat muscle-derived progenitor cells (MDCs).
MDCs were isolated from rat skeletal muscle and purified using the preplate technique. For in vitro tests, the MDCs underwent either 2 hours of, or continuous, exposure to lidocaine (50 microM-5 mM). After 72 hours of incubation, cell viability was measured using the methylthiazololetetrazolium assay. For the in vivo tests, periurethral injection of either phosphate-buffered saline, MDCs (1 x 10(6) cells/20 microL), or 2% lidocaine plus MDCs was performed in pudendal nerve-transected rats. The leak point pressure (LPP) was measured at 4 weeks after the injection.
Lidocaine concentrations of < or = 500 microM had no effect on MDCs with continuous exposure. MDCs in 1 mM lidocaine showed decreased survival and no MDCs in 5 mM lidocaine survived. With a 2-hour exposure, only MDCs in the 5-mM lidocaine group showed decreased survival. Rats with nerve transection and phosphate-buffered saline injection showed significantly lower LPPs than the controls. The LPP was restored to a significantly greater level after MDCs only or lidocaine plus MDC injection. No statistically significant difference in LPP restoration was found between the MDC-only and lidocaine plus MDC injections.
Cytotoxicity to lidocaine was minimal at a physiologic concentration in vitro. The functional recovery of LPP by MDC treatment was not affected by lidocaine preinfiltration. Taken together, our data indicate that lidocaine can be applied as a local anesthetic in periurethral MDC injection without decreasing the efficacy of the therapy.
已有报道称利多卡因对某些细胞类型具有细胞毒性,这可能会影响其在基于细胞的治疗中作为局部麻醉剂的使用。我们评估了利多卡因对大鼠肌肉来源祖细胞(MDCs)的体外和体内作用。
从大鼠骨骼肌中分离出MDCs,并使用预板技术进行纯化。对于体外试验,将MDCs暴露于利多卡因(50微摩尔/升至5毫摩尔/升)2小时或持续暴露。孵育72小时后,使用甲基噻唑基四氮唑蓝法测量细胞活力。对于体内试验,在阴部神经切断的大鼠中进行尿道周围注射磷酸盐缓冲盐水、MDCs(1×10⁶个细胞/20微升)或2%利多卡因加MDCs。在注射后4周测量漏点压力(LPP)。
持续暴露时,利多卡因浓度≤500微摩尔/升对MDCs无影响。1毫摩尔/升利多卡因中的MDCs存活率降低,5毫摩尔/升利多卡因中无MDCs存活。暴露2小时时,仅5毫摩尔/升利多卡因组的MDCs存活率降低。神经切断并注射磷酸盐缓冲盐水的大鼠的LPP显著低于对照组。仅注射MDCs或利多卡因加MDCs后,LPP恢复到显著更高水平。仅注射MDCs与利多卡因加MDCs注射之间在LPP恢复方面未发现统计学上的显著差异。
在体外生理浓度下,利多卡因的细胞毒性极小。MDC治疗对LPP的功能恢复不受利多卡因预浸润的影响。综上所述,我们的数据表明利多卡因可作为尿道周围MDC注射的局部麻醉剂,而不会降低治疗效果。