Lidocaine cytotoxicity to the bovine articular chondrocytes in vitro: changes in cell viability and proteoglycan metabolism

Purpose A lot of studies on the effect of intra-articular injections are clinical, but many questions on the effect of lidocaine to articular chondrocytes remain unanswered. This study was performed to determine the effects of varying concentrations and exposure times of lidocaine on the viability a...

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Published in:Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA sports traumatology, arthroscopy : official journal of the ESSKA, 2011-07, Vol.19 (7), p.1198-1205
Main Authors: Miyazaki, Tsuyoshi, Kobayashi, Shigeru, Takeno, Kenichi, Yayama, Takafumi, Meir, Adam, Baba, Hisatoshi
Format: Article
Language:English
Subjects:
Anesthetics, Local - toxicity
Animals
Arthritis
Blood
Cartilage
Cartilage, Articular - cytology
Cartilage, Articular - drug effects
Cattle
Cell culture
Cell Survival - drug effects
Chondrocytes - drug effects
Chondrocytes - metabolism
Cytotoxicity
Dose-Response Relationship, Drug
Experimental Study
Glycosaminoglycans - metabolism
In Vitro Techniques
Injections
Joints
Knee
Lactic acid
Lactic Acid - metabolism
Lidocaine - toxicity
Male
Measurement
Medicine
Medicine & Public Health
Metabolism
Metatarsus
Microscopy, Electron, Transmission
Orthopedics
Osteoarthritis
Proteoglycans - metabolism
Sports
Surgery
Time Factors
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Summary:Purpose A lot of studies on the effect of intra-articular injections are clinical, but many questions on the effect of lidocaine to articular chondrocytes remain unanswered. This study was performed to determine the effects of varying concentrations and exposure times of lidocaine on the viability and proteoglycan metabolism of chondrocytes in vitro. Method Cartilage was obtained from metatarsal joints of adult bovines. Chondrocytes in alginate beads were cultured in medium containing 6% fetal calf serum at 370 mOsmol at cell densities of 4 million cells/ml. They were then cultured for 24 h under 21% oxygen with 0.125, 0.25, 0.5, and 1% lidocaine and without lidocaine as control. The cell viability profile across intact beads was determined by manual counting using fluorescent probes and transmission electron microscopy. Result Lactate production was measured enzymatically as a marker of energy metabolism. Glycosaminoglycan (GAG) accumulation was measured using a modified dimethylmethylene blue assay. Cell viability decreased in a time- and dose-dependent manner in the concentration range of 0.125–1.0% lidocaine under the confocal microscope. Under the electron microscope, apoptosis increased as the concentration of lidocaine increased. GAG accumulation/tissue volume decreases as the concentration of lidocaine increased. However, GAG produced per million cells and the rate of lactate production per live cell were significantly higher for cells cultured at 0.5 and 1% lidocaine than the control group. Bovine chondrocytes cultured in alginate beads under high oxygen pressure are negatively influenced by increasing concentrations of lidocaine. Conclusion Cell viability and proteoglycan production (GAG accumulation/tissue volume) decreased as the concentration of lidocaine increased. These data suggest caution in prolonged exposure of cartilage to high concentration lidocaine. Repeated joint injection of lidocaine potentially worsens osteoarthrosis by accelerating cartilage degradation. Level of evidence Therapeutic studies—investigating the results of treatment, Level III.
ISSN:0942-2056
1433-7347
DOI:10.1007/s00167-010-1369-9