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A992
October 17, 2011
8:00:00 AM - 11:00:00 AM
Room Hall B2 Area G
Effects of Local Anesthetics on Human Cells Mitochondrial Metabolism from Patients with Mitochondrial Disease
Karine Nouette-Gaulain, M.D.,Ph.D., Emilie GIRAUD, Ph.D., Caroline Espil-Tarris, M.D., Didier Lacombe, M.D.,Ph.D., Xavier Capdevila, M.D.,Ph.D., Rodrigue Rossignol, Ph.D.
Université Segalen Bordeaux 2, Bordeaux, France
Introduction:

The local anesthetic-induced myotoxicity is explained partially by the interaction between the local anesthetics (LA) and energy mitochondrial metabolism (1). Nevertheless, the effect of LA on patient with mitochondrial diseases cells is not described and the risk remains to evaluate. This question is important because the muscle biopsies are performed with LA wound infiltration. The objective of this work was to evaluate the effect of increasing doses of lidocaine and ropivacaine on the energy mitochondrial metabolism, on oxidative stress, on cells from different patients with mitochondria diseases.

Methods:

Human cell lines from patients with mitochondria diseases (Leber, BMM, OPA3, FMM) and from control patients (C1 and C2) were investigated. Cells were treated during one hour with different concentrations of lidocaine or ropivacaine (1 µM, 100 µM, 500 µM, 1 mM, 3 mM). We analyzed cell proliferation (numbered after treatment), oxygen consumption ( SeaHorse), oxidative stress (CM-H2DCFDA by fluorometry) and the potential of mitochondrial membrane (measured using fluorometry with TMRM). The morphology of the mitochondrial network was observed using fluorescence microscopy (Mitotracker - Zeiss Vivatome). Data are expressed as mean ± SD

Results

After one hour of 100µM ropivacaïne treatment, oxidative phosphorylation decoupling is significantly increased in cells from patients with mitochondrial diseases in comparison with controls (oxygen consumption: Leber 143.6 % ±15.6 vs C1 108.9 % ± 15 %, P=0.04). The membrane potential is significantly decreased (Leber 84.4 % ± 0.6 % vs C1 91 % ± 1.5 %, P=0.002), the production of reactive oxygen species is significantly increased (Leber 292 % ± 1.8 vs C1 129.1 % ± 7, P=0.002). On the other hand, according to the mitochondrial disease, these differences are more or less observed. After one hour of 100µM lidocaine treatment, significant differences between cells from patients with mitochondrial disease (Leber) and from control patients were not observed.

Discussion

The LA toxicity is enhanced in cells from patients with mitochondrial diseases. This toxicity is essentially observed with the ropivacaine, very often used for wound infiltrations during the muscle biopsies. The interpretation of the results should integrate the type of LA used during biopsy. Additional experiments will permit to characterize more precisely the differences observed between the two local anesthetics.

Copyright © 2011 American Society of Anesthesiologists