Milutinovic Pavle S, Zhao Jing, Sonner James M
The University of Pittsburg School of Medicine,Pittsburgh, Pennsylvania, USA.
Anesth Analg. 2009 Jan;108(1):176-80. doi: 10.1213/ane.0b013e31818ca33e.
Tolerance is observed for a variety of central nervous system depressants including ethanol, which is an anesthetic, but has not been convincingly demonstrated for a potent halogenated volatile anesthetic. Failure to demonstrate tolerance to these agents may be the result of inadequate exposure to anesthetic. In this study, we exposed Xenopus laevis tadpoles to surgical anesthetic concentrations of isoflurane for 1 wk.
Xenopus laevis tadpoles were produced by in vitro fertilization, and exposed to isoflurane (0.59%, 0.98%, 1.52%) or oxygen for 1 wk starting from the time of fertilization.
Changes in anesthetic EC(50) were small and not in a consistent direction. Control animals had an anesthetic EC(50) of 0.594% +/- 0.003% isoflurane. Tadpoles exposed to 1.52% isoflurane had a lower EC(50) than controls (by 16%), whereas tadpoles raised under 0.59% and 0.98% isoflurane had higher EC(50)s than control (by 4.7% and 7.4%, respectively).
We provide the first description of week-long exposures of vertebrates to surgical anesthetic concentrations of isoflurane, and the first report of such exposures in developing vertebrates. Tolerance to isoflurane does not occur in developing Xenopus laevis tadpoles. Taken together with studies in other organisms, the development of tolerance to ethanol but not isoflurane suggests that mechanisms shared by these drugs probably do not account for the development of tolerance.
人们观察到对包括乙醇在内的多种中枢神经系统抑制剂存在耐受性,乙醇是一种麻醉剂,但对于强效卤化挥发性麻醉剂,尚未有令人信服的耐受性证明。未能证明对这些药物的耐受性可能是由于麻醉暴露不足所致。在本研究中,我们将非洲爪蟾蝌蚪暴露于手术麻醉浓度的异氟烷中1周。
通过体外受精产生非洲爪蟾蝌蚪,并从受精时起将其暴露于异氟烷(0.59%、0.98%、1.52%)或氧气中1周。
麻醉半数有效浓度(EC50)的变化很小且方向不一致。对照动物的异氟烷麻醉EC50为0.594%±0.003%。暴露于1.52%异氟烷的蝌蚪的EC50低于对照组(低16%),而在0.59%和0.98%异氟烷环境下饲养的蝌蚪的EC50高于对照组(分别高4.7%和7.4%)。
我们首次描述了脊椎动物在手术麻醉浓度的异氟烷下暴露一周的情况,也是首次报道在发育中的脊椎动物中的此类暴露。发育中的非洲爪蟾蝌蚪对异氟烷不存在耐受性。结合其他生物体的研究,对乙醇产生耐受性而对异氟烷不产生耐受性表明,这些药物共有的机制可能无法解释耐受性的产生。