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ANESTHETIC PHARMACOLOGY

Alterations in Spinal, but Not Cerebral, Cerebrospinal Fluid Na⁺ Concentrations Affect the Isoflurane Minimum Alveolar Concentration in Rats

Michael J. Laster, DVM^*, Yi Zhang, MD, Edmond I. Eger, II, MD^*, Dimitry Shnayderman, BS^*, and James M. Sonner, MD^*

From the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; and Department of Anesthesiology, Fuwai Hospital and Cardiovascular Institute, Beijing, China.

Address correspondence and reprint requests to Edmond I Eger, II, MD, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464. Address e-mail to egere{at}anesthesia.ucsf.edu.

BACKGROUND: Previous studies demonstrated that MAC (the minimum alveolar concentration of an inhaled anesthetic that produces immobility in 50% of subjects exposed to noxious stimulation) for halothane directly correlates with the central nervous system concentration of Na⁺. However, those studies globally altered Na⁺ concentrations, and thus did not distinguish effects on the spinal cord from cerebral effects. This is an important distinction because the cord appears to be the primary site for mediation of the immobility produced by inhaled anesthetics. Accordingly, in the present study, we examined the effect of altering intrathecal versus intracerebroventricular concentrations of Na⁺ on MAC.

METHODS: In rats prepared with chronic indwelling catheters or stylets, we infused solutions deficient in Na⁺ and with an excess of Na⁺ into the lumbar subarachnoid and intracerebroventricular spaces and measured MAC for isoflurane before, during, and after infusion.

RESULTS: MAC of isoflurane correlated directly with concentrations of Na⁺ infused intrathecally but did not correlate with concentrations infused intracerebroventricularly.

CONCLUSION: The results are consistent with a mediation or modulation of MAC by Na⁺ channels. These might include voltage-gated or ligand-gated channels or other Na-sensitive targets (e.g., pumps, transporters, exchangers).

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