Karabulut A K, Reisli R, Uysal I I, Celik J B, Ziylan T
Selcuk University, Meram Faculty of Medicine, Department of Anatomy, Konya, Turkey.
Eur J Anaesthesiol. 2004 Sep;21(9):715-24. doi: 10.1017/s0265021504009081.
We have investigated the toxic and teratogenic effects of certain non-depolarizing muscle relaxants on embryonic development in cultured rat embryos.
Rat embryos of 9.5 days were explanted and cultured in vitro for 48 h in rat serum. Whole rat serum was used as a culture medium for the control group while different concentrations of atracurium, cis-atracurium, rocuronium and mivacurium were added to rat serum for the experimental groups. Dose-dependent effects of these agents on embryonic developmental parameters were compared using morphological and biochemical methods. Each embryo was evaluated for the presence of any malformations.
When compared to the control embryos, the muscle relaxants significantly decreased all growth and developmental parameters dose dependently with an increase in overall dismorphology. Among these malformations, maxillary deformity was most frequently observed. These effects were observed in much lower doses with atracurium and cis-atracurium compared to those with rocuronium and mivacurium.
Our results suggest that non-depolarizing muscle relaxants cause dose-dependent toxicity on rat embryos at concentrations much greater than those in clinical practice. Although, these agents seems to have a low potential for causing developmental toxicity during organogenesis, because of the lower toxic effects observed with rocuronium and mivacurium, these agents may be preferred when recurrent administrations are necessary for parturients.
我们研究了某些非去极化肌松药对培养的大鼠胚胎发育的毒性和致畸作用。
取9.5日龄的大鼠胚胎,在大鼠血清中进行体外培养48小时。对照组使用全大鼠血清作为培养基,实验组则在大鼠血清中添加不同浓度的阿曲库铵、顺式阿曲库铵、罗库溴铵和米库氯铵。使用形态学和生化方法比较这些药物对胚胎发育参数的剂量依赖性影响。评估每个胚胎是否存在任何畸形。
与对照胚胎相比,肌松药显著降低了所有生长和发育参数,且呈剂量依赖性,整体畸形增加。在这些畸形中,上颌畸形最为常见。与罗库溴铵和米库氯铵相比,阿曲库铵和顺式阿曲库铵在低得多的剂量下就观察到了这些效应。
我们的结果表明,非去极化肌松药在远高于临床实践中的浓度下对大鼠胚胎产生剂量依赖性毒性。虽然这些药物在器官发生期间似乎引起发育毒性的可能性较低,但由于罗库溴铵和米库氯铵观察到的毒性作用较低,当产妇需要反复给药时,这些药物可能更受青睐。