PROPOFOL REDUCES NEURONAL TRANSMISSION DAMAGE AND ATTENUATES THE CHANGES IN CALCIUM, POTASSIUM, AND SODIUM DURING HYPERTHERMIC ANOXIA IN THE RAT HIPPOCAMPAL SLICE

Background: Propofol reduces cerebral blood flow, cerebral metabolic r ate for oxygen, and intracranial pressure and is being increasingly us ed in neuroanesthesia. In vivo studies have yielded conflicting result s on its ability to protect against ischemic brain damage, In the curr ent study, an in vitro model was used to examine the mechanism of prop ofol's action on anoxic neuronal transmission damage. Methods: A presy naptic pathway was stimulated In the rat hippocampal slice to elicit a postsynaptic population spike in the CAI region, The effects of propo fol (20 mu g/ml), its solvent intralipid or no drug, on the population spike before, during, and 60 min after anoxia at 37 degrees C or 39 d egrees C were examined, Intracellular adenosine triphosphate (ATP), Na , and K were measured in dissected CAI regions at 37 degrees C and 39 degrees C after 5 min of anoxia; Ca-45 influx was measured after 10 mi n of anoxia. Results: Propofol did not improve recovery after 5, 6, or 7 min of anoxia at 37 degrees C, Recovery of the population spike aft er 6 min of anoxia at 37 degrees C was 62 +/- 11% with propofol, 35 +/ - 15% with intralipid, and 44 +/- 10% in untreated tissue (NS), After 5 min of anoxia at 39 degrees C, there was significantly better recove ry of the population spike with propofol (76 +/- 12%) than with intral ipid (11 +/- 6%) or no drug (13; +/- 5%), Propofol, but not intralipid , reduced the population spike amplitude before anoxia. At 37 degrees C, anoxia caused significant changes in ATP (62% of normoxic concentra tion), Ca (115%), Na (138%), and K (68%). Both propofol and intralipid significantly attenuated the changes in ATP (78% and 82% of normoxic concentration) and Ca (104% and 103%), Na changes were attenuated by p ropofol (95%) but not intralipid; K concentration was not affected by either drug. At 33 degrees C, for most parameters, anoxia caused more marked changes: ATP was 23% of nonmoxic concentration, Ca 116%, Na 185 %, and K 48%. Both propofol and intralipid attenuated the decrease in ATP (56% of normoxic); propofol, but not intralipid, significantly att enuated the changes in Ca (100%), Na (141%), and K (63%). Conclusions: Propofol improved electrophysiologic recovery from anoxia during hype rthermia but not normothermia. At 37 degrees C propofol attenuated the changes in ATP, Na, and Ca, however, this did not result in improved recovery. At 39 degrees C the changes in ATP, Na, and K caused by anox ia were greater than at 37 degrees C; this could explain why electroph ysiologic damage was worsened. Improved recovery with propofol at 39 d egrees C may be explained by its attenuation of the changes in Ca, Na, and K at this temperature. The decrease in ATP was attenuated by both propofol and intralipid and therefore cannot explain the improved rec overy.