Is the chronic administration of Propofol really safe?

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591812
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: University of Miyazaki
• Principal Investigator: NARUO Hiroaki University of Miyazaki, Anesthesiology, Assistant, 医学部, 助手 (10274797)
• Project Period (FY): 2004 – 2005
• Keywords: propofol / synaptic transmission / synaptic plasticity / Lymnaea

Research Abstract

The period of quieting down of patient in ICU sometimes reaches a long term, so injured nervous tissue are exposed to propofol for long-term. Following sterile dissection, the central ring ganglia will be isolated and after antibiotic washes and enzyme treatment individual neurons will be extract from the intact brain., General suction pressure will be applied to extract the somata of individual cells and plated on Poly-L-lysine coated dishes containing CM. Soma-soma synapses were prepared by juxtaposing the isolated somata of identified neurons. Specifically, identified presynaptic neuron (visceral dorsal 4 (VD4)) was isolated and paired with its postsynaptic partner (left pedal dorsal 1 (LPeD1)), and synapses were allowed to develop overnight in CM.
1.To test whether propofol affects synaptic transmission between VD4 and LPeD1, synapses were tested in either the absence or the presence of propofol (25μM, 50μM, 100μM). Propofol delivered through a fast perfusion system directly at the contact site suppressed synaptic transmission in a dose dependent manner.(25μM : 84.1%, 50μM : 67.9%, 100μM : 24.4%). These data demonstrate that propofol blocks synaptic transmission between VD4 and LPeD1 dose dependent manner.
2.To test for the effects of propofol on short-term synaptic plasticity, synapse were reconstructed overnight. After a single action potential in VD4 that generated 1:1 EPSPs in LPeD1, a tetanus(8-10 action potentials) was delivered to VD4. Subsequent action potentials in VD4 delivered within a few seconds of the tetanus resulted in postsynaptic potentiation. These experiments will demonstrate that whether propofol affect the genesis of PTP at this synapse or not. It is a stage where the data is being acquired now.