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利多卡因对体外培养的大鼠胚胎致畸作用的评估。

Assessment of teratogenic effects of lidocaine in rat embryos cultured in vitro.

作者信息

Fujinaga M

机构信息

Department of Anesthesia, Stanford University School of Medicine, California, USA.

出版信息

Anesthesiology. 1998 Dec;89(6):1553-8. doi: 10.1097/00000542-199812000-00035.

Abstract

BACKGROUND

Lidocaine has been reported to cause neural tube closure defects in vitro in mice at clinically relevant concentrations. However, no studies have been conducted to further investigate this potentially hazardous effect of lidocaine. This study was aimed to reassess teratogenic effects of lidocaine in vitro in rats.

METHODS

Sprague-Dawley rat embryos were explanted at 8:00 AM on gestational day 9 and were cultured in medium containing various concentrations of lidocaine. (Embryos in the control group were cultured without lidocaine). After 50 h of culture, they were evaluated for growth size and morphology, including the neural tube closure.

RESULTS

In the presence of 250 microM of lidocaine, embryos showed a increased incidence of situs inversus compared with control group but were otherwise normal. At 375 microM, embryos showed slight growth retardation but no significant morphologic abnormalities. At 500 microM, all viable embryos showed severe morphologic abnormalities. However, morphologic abnormalities were so-called nonspecific types and neural tube closure defects were not observed.

CONCLUSIONS

Results from the current study indicate that lidocaine causes teratogenic effects in vitro in rats only at concentrations much higher than clinically relevant concentrations. Furthermore, lidocaine did not cause neural tube closure defects at any concentrations evaluated.

摘要

背景

据报道,利多卡因在体外实验中,在临床相关浓度下可导致小鼠神经管闭合缺陷。然而,尚未开展进一步研究来探究利多卡因的这种潜在有害作用。本研究旨在重新评估利多卡因在体外对大鼠的致畸作用。

方法

在妊娠第9天上午8点取出斯普拉格-道利大鼠胚胎,培养于含有不同浓度利多卡因的培养基中。(对照组胚胎在无利多卡因的情况下培养)。培养50小时后,评估其生长大小和形态,包括神经管闭合情况。

结果

在存在250微摩尔利多卡因的情况下,与对照组相比,胚胎出现内脏反位的发生率增加,但其他方面正常。在375微摩尔时,胚胎显示出轻微的生长迟缓,但无明显形态学异常。在500微摩尔时,所有存活胚胎均出现严重形态学异常。然而,形态学异常为所谓的非特异性类型,未观察到神经管闭合缺陷。

结论

本研究结果表明,利多卡因仅在远高于临床相关浓度时才会在体外对大鼠产生致畸作用。此外,在评估的任何浓度下,利多卡因均未导致神经管闭合缺陷。

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