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October 20, 2009
3:00 PM - 4:30 PM
Room Room 356
Subthalamic Neurons Recorded in Humans Are Differentially Altered by Propofol and Remifentanil
  **   Bruce MacIver, M.Sc., Ph.D., John Brock-Utne, M.D., Ph.D. F.R.C.P., Richard Jaffe, M.D., Ph.D.
Anesthesia, Stanford University School of Medicine, Stanford, California
Introduction: Neurons of the subthalamic nucleus (STN) exhibit discharge activity that is correlated with normal movement and motor abnormalities in Parkinson's disease (PD). In rat brain slices, STN neurons are unique in that they spontaneously discharge single spikes in the absence of synaptic input and appear to lack GABA-mediated tonic currents. In studies of human PD patients receiving STN electrode implants we compared the effects of low-dose propofol or remifentanil on neuronal discharge activity. To further characterize the target sites for propofol and remifentanil, we studied the actions of these agents on spontaneous spike firing in rat STN brain slices.

Methods: Following IRB approval, patients undergoing DBS implant surgery were given bolus injections of either propofol (0.3 mg/Kg) or remifentanil (0.8 µg/Kg) and STN action potential discharge activity was recorded before (2 min) and after (10 to 15 min) injections. Following IRB approval, 400 µm thick brain slices were prepared from male Sprague-Dawley rats (P 20 to 25). Slices were maintained in submerged chambers at 22°C and continuously perfused with artificial cerebrospinal fluid (ACSF). Action potential discharge activity and synaptic currents were monitored with extracellular glass microelectrodes filled with ASCF or using whole cell patch clamp recordings with standard procedures.

Results: In human studies using either propofol or remifentanil only minor effects on discharge activity of STN neurons were observed, including no change in spike amplitude, rise time or undershoot potential. However, action potentials of STN neurons with short inter-spike intervals (less than 10 ms) were markedly reduced and longer intervals were evident in the presence of propofol, even though overall discharge rates (5 s bin widths) remained stable. Similarly, little overall change in discharge frequency was produced by remifentanil, and no change in fast spiking activity was seen, however, discharge patterns became some what more burst-like. Whole cell recordings of STN neurons in rat brain slices demonstrated that propofol prolonged GABA-mediated synaptic currents, similar to effects seen in other types of neurons. This occurred with no change in membrane conductance or evoked action potential discharge responses – consistent with the lack of depression seen in human recordings.

Conclusions: Propofol prolonged GABA-mediated synaptic inhibition and this appeared to contribute to the reduced high frequency activity that we observed in human PD patients. Remifentanil, in contrast, did not appear to increase the duration of inhibition, and may even depress inhibition somewhat, leading to increased burst firing. Neither agent appeared to produce tonic depression of STN discharge in patients. Thus both propofol and/or remifentanil could be useful as sedatives during DBS implant surgeries.

Supported by Stanford Anesthesia.

From Proceedings of the 2009 Annual Meeting of the American Society Anesthesiologists.