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ANESTHETIC PHARMACOLOGY

Tolerance to Isoflurane Does Not Occur in Developing Xenopus laevis Tadpoles

Pavle S. Milutinovic, MS^*, Jing Zhao, MD, and James M. Sonner, MD

From the *The University of Pittsburg School of Medicine, Pittsburgh, Pennsylvania; Peking Union Medical College, Peking, China; and The Department of Anesthesia and Perioperative Care, University of California, San Francisco, California.

Address correspondence to Dr. James M. Sonner, Department of Anesthesia and Perioperative Care, Room S-455i, University of California, San Francisco, CA 94143-0464. Address e-mail to sonnerj{at}anesthesia.ucsf.edu.

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 EC₅₀ were small and not in a consistent direction. Control animals had an anesthetic EC₅₀ of 0.594% ± 0.003% isoflurane. Tadpoles exposed to 1.52% isoflurane had a lower EC₅₀ than controls (by 16%), whereas tadpoles raised under 0.59% and 0.98% isoflurane had higher EC₅₀s 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.

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