In vitro and in vivo effect of lidocaine on rat muscle-derived cells for treatment of stress urinary incontinence.

ABSTRACT

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.