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• W2079247263 abstract "To investigate the mechanism by which rare cases of spinal local anesthetic (LA) neurotoxicity occur, we have tested the hypotheses that LAs elevate cytoplasmic calcium (Ca2+(cyt)), that this is associated with a neurotoxic effect, and that lidocaine and bupivacaine differ in their neurotoxicity.Neurons of the ND7 cell culture line, derived from dorsal root ganglion, were loaded with fura-2 and analyzed by digitized video fluorescence microscopy during 60 min LA exposure, allowing determination of Ca2+(cyt) and time of necrotic cell death (plasma membrane lysis) at the single neuron level.Lidocaine 0.1% and bupivacaine 0.025% caused minimal changes in Ca. Lidocaine 0.5-5% and bupivacaine 0.125-0.625% caused an early, small (less than threefold), concentration-dependent increase in Ca2+(cyt) that was transient and returned to near baseline within 10 min. Lidocaine 2.5% and 5% then caused a sustained, greater than ten-fold increase in Ca2+(cyt) and death in some neurons during the 60 min exposure period. Pretreatment with thapsigargin eliminated the initial transient increase in Ca2+(cyt), consistent with endoplasmic reticulum (ER) as its source, and increased neuronal death with 5% lidocaine, suggesting that lidocaine neurotoxicity can be increased by failure of ER to take up elevated Ca2+(cyt). The later sustained increase in Ca2+(cyt) seen with 2.5 and 5% lidocaine was prevented in Ca2+ -free medium, and restored when Ca2+ was added back to the buffer in the presence of lidocaine, suggesting that higher concentrations of lidocaine increase influx of Ca2+ through the plasma membrane.In this model, lidocaine greater than 2.5% elevates Ca2+(cyt) to toxic levels. Bupivacaine and lower concentrations of lidocaine transiently alter Ca2+(cyt) homeostasis for several minutes, but without an immediate neurotoxic effect within 60 min." @default.
• W2079247263 created "2016-06-24" @default.
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• W2079247263 date "2002-12-01" @default.
• W2079247263 modified "2023-09-26" @default.
• W2079247263 title "Effect of Local Anesthetic on Neuronal Cytoplasmic Calcium and Plasma Membrane Lysis (Necrosis) in a Cell Culture Model" @default.
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• W2079247263 doi "https://doi.org/10.1097/00000542-200212000-00019" @default.
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