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IN VITRO PROTECTION AGAINST CEREBRAL HYPOXIABY LOCAL ANESTHETICS

CATHERINE A. WEST-PHELAN, AVITAL SCHURR, LINDA F. LUCAS and BENJAMINE M, RIGOR, Department of Anesthesiology, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.

Numerous studies have been published in recent years on potential antihypoxic drugs and their pharmacology, where many of them employed in vivo models of cerebral ischemia/hypoxia. For faster and less expensive screening of such drugs we have been using the in vitro rat hippocampal slice preparation. In a recent study we demonstrated the depressive effect of lidocaine on synaptic function using this in vitro system. If such depression is the result of metabolic arrest or ion fluxes attenuation, then lidocaine and other similar local anesthetics should exhibit antihypoxic properties.

Rat hippocampal slices were incubated with non-depressive doses of either lidocaine, 2-chloroprocaine or cocaine 60 min prior to their exposure to 15 min hypoxia. The rate of recovery of synaptic function (evoked population spike) following the hypoxic episode was used as an index of hypoxic damage. Slices treated with 0.i mM of any of the three local anesthetics exhibited a significant increase in the recovery rate of synaptic function from hypoxia as conpared to control, untreated slices.

These results indicate that the ability of local aneskhetics to either reduce neuronal Na + influx (and possibly its concomitant Ca 2+ influx) upon hypoxic depolarization, or to conserve ATP via metabolic slow down or both, is responsible for their antihypoxic properties.