The differential effects of volatile anesthetics on electrophysiological and biochemical changes during and recovery after hypoxia in rat hippocampal slice CA1 pyramidal cells.

摘要

Two volatile agents, isoflurane and sevoflurane have similar anesthetic properties but different potencies; this allows the discrimination between anesthetic potency and other properties on the protective mechanisms of volatile anesthesia. Two times the minimal alveolar concentration of an anesthetic is approximately the maximally used clinical concentration of that agent; this concentration is 2% for isoflurane and 4% for sevoflurane. We measured the effects of isoflurane and sevoflurane on cornus ammonis 1 (CA1) pyramidal cells in rat hippocampal slices subjected to 10 min of hypoxia (95% nitrogen 5% carbon dioxide) and 60 min of recovery. Anesthetic was delivered to the gas phase using a calibrated vaporizer for each agent. At equipotent anesthetic concentrations, sevoflurane (4%) but not isoflurane (2%), enhanced the initial hyperpolarization (6.7 vs. 3.4 mV), delayed the hypoxic rapid depolarization (521 vs. 294 s) and reduced peak hypoxic cytosolic calcium concentration (203 vs. 278 nM). While both agents reduced the final membrane potential at 10 min of hypoxia compared with controls, 4% sevoflurane had a significantly greater effect than 2% isoflurane (-24.4 vs. -3.5 mV). The effect of these concentrations of isoflurane and sevoflurane was not different for sodium, potassium or ATP concentrations at 10 min of hypoxia, the only difference at 5 min of hypoxia was that ATP was better maintained with 4% sevoflurane (2.2 vs. 1.3 nmol/mg). If the same absolute concentration (4%) of isoflurane and sevoflurane is compared then the cellular changes during hypoxia are similar for both agents and they both improve recovery. We conclude that an anesthetic's absolute concentration and not its anesthetic potency correlates with improved recovery of CA1 pyramidal neurons. The mechanisms of sevoflurane-induced protection include delaying and attenuating the depolarization and the increase of cytosolic calcium and delaying the fall in ATP during hypoxia.