Tolerance to isoflurane does not occur in developing Xenopus laevis tadpoles

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Fig 1

Xenopus laevis tadpoles were produced by in vitro fertilization and raised from conception until one week of age in air (control), or in air with 0.59, 0.98, or 1.52 % atmospheres (% atm) isoflurane. Isoflurane EC₅₀ was determined at one week of age. This figure shows the fraction of tadpoles moving in response to prodding as a function of isoflurane concentration. EC₅₀s are open circles, with horizontal error bars representing the standard error in the EC₅₀.

Fig 2

Xenopus laevis tadpoles were raised from zygotes to one week old tadpoles in air, or in air with 0.59, 0.98, or 1.52 % atmospheres isoflurane. The fraction of tadpoles that were healthly (did not die and had no morphological abnormalities) on days 4, 6, and 7/8 is shown here (some animals were studied on day 7, and some on day 8; these results were pooled and are denoted 7/8). At 4 days, there was no difference in survival among control animals or animals raised in any concentration of isoflurane. Animals exposed to 0.98% isoflurane and 1.52% isoflurane began to die or develop morphological abnormalities by day 6.

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