Skip to main content
Top
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 7/2011

01-07-2011 | Experimental Study

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

Authors: Tsuyoshi Miyazaki, Shigeru Kobayashi, Kenichi Takeno, Takafumi Yayama, Adam Meir, Hisatoshi Baba

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 7/2011

Login to get access

Abstract

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.
Literature
1.
go back to reference Bojescul JA, Wilson G, Taylor DC (2005) Idiopathic chondrolysis of the ankle. Arthroscopy 21:224–227PubMedCrossRef Bojescul JA, Wilson G, Taylor DC (2005) Idiopathic chondrolysis of the ankle. Arthroscopy 21:224–227PubMedCrossRef
2.
go back to reference Chiang N, Schwab JM, Fredman G et al (2008) Anesthetics impact the resolution of inflammation. PloS ONE 3:e1879PubMedCrossRef Chiang N, Schwab JM, Fredman G et al (2008) Anesthetics impact the resolution of inflammation. PloS ONE 3:e1879PubMedCrossRef
3.
go back to reference Chu CR, Izzo NJ, Coyle CH et al (2008) The in vivo effects of bupivacaine on articular chondrocytes. J Bone Joint Surg 90B:814–820 Chu CR, Izzo NJ, Coyle CH et al (2008) The in vivo effects of bupivacaine on articular chondrocytes. J Bone Joint Surg 90B:814–820
4.
go back to reference Chunekamrai S, Krook LP, Lust G et al (1989) Changes in articular cartilage after intra-articular injections of methylprednisolone acetate into equine joints. Am J Vet Res 50:1733–1741PubMed Chunekamrai S, Krook LP, Lust G et al (1989) Changes in articular cartilage after intra-articular injections of methylprednisolone acetate into equine joints. Am J Vet Res 50:1733–1741PubMed
5.
go back to reference Dogan N, Erdem AF, Erman Z et al (2004) The effects of bupivacaine and neostigmine on articular cartilage and synovium in the rabbit knee joint. J Int Med Res 32:513–519PubMed Dogan N, Erdem AF, Erman Z et al (2004) The effects of bupivacaine and neostigmine on articular cartilage and synovium in the rabbit knee joint. J Int Med Res 32:513–519PubMed
6.
go back to reference Dragoo JL, Korotkova T, Kanwar R et al (2008) The effect of local anesthetics administered via pain pump on chondrocyte viability. Am J Sports Med 36:1484–1488PubMedCrossRef Dragoo JL, Korotkova T, Kanwar R et al (2008) The effect of local anesthetics administered via pain pump on chondrocyte viability. Am J Sports Med 36:1484–1488PubMedCrossRef
7.
go back to reference Enobakhare BO, Bader DL, Lee DA (1996) Quantification of sulfated glycosaminoglycans in chondrocyte/alginate culture, by use of 1,9-dimethylmethylene blue. Anal Biochem 243:189–191PubMedCrossRef Enobakhare BO, Bader DL, Lee DA (1996) Quantification of sulfated glycosaminoglycans in chondrocyte/alginate culture, by use of 1,9-dimethylmethylene blue. Anal Biochem 243:189–191PubMedCrossRef
8.
go back to reference Foster AH, Carlson BM (1980) Mycotoxicity of local anesthetics and regeneration of the damaged muscle fibers. Anesth Analg 59:727–736PubMedCrossRef Foster AH, Carlson BM (1980) Mycotoxicity of local anesthetics and regeneration of the damaged muscle fibers. Anesth Analg 59:727–736PubMedCrossRef
9.
go back to reference Friederich P, Schmitz TP (2002) Lidocaine-induced cell death in a human model of neuronal apoptosis. Eur J Anaesthesiol 19:564–570PubMed Friederich P, Schmitz TP (2002) Lidocaine-induced cell death in a human model of neuronal apoptosis. Eur J Anaesthesiol 19:564–570PubMed
10.
go back to reference Gray M, Pizzanelli A, Grodzinsky A et al (1988) Mechanical and physiochemical determinants of the chondrocyte biosynthetic response. J Orthop Res 6:777–792PubMedCrossRef Gray M, Pizzanelli A, Grodzinsky A et al (1988) Mechanical and physiochemical determinants of the chondrocyte biosynthetic response. J Orthop Res 6:777–792PubMedCrossRef
11.
go back to reference Grimshaw MJ, Mason RM (2000) Bovine articular chondrocyte function in vitro depends upon oxygen tension. Osteoarthr Cartil 8:386–392PubMedCrossRef Grimshaw MJ, Mason RM (2000) Bovine articular chondrocyte function in vitro depends upon oxygen tension. Osteoarthr Cartil 8:386–392PubMedCrossRef
12.
go back to reference Grouselle M, Tueux O, Dabadie P et al (1990) Effect of local anaesthetics on mitochondrial membrane potential in living cells. Biochem J 271:269–272PubMed Grouselle M, Tueux O, Dabadie P et al (1990) Effect of local anaesthetics on mitochondrial membrane potential in living cells. Biochem J 271:269–272PubMed
13.
go back to reference Guo JF, Jourdian GW, Maccallu DK (1989) Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res 19:277–297PubMedCrossRef Guo JF, Jourdian GW, Maccallu DK (1989) Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res 19:277–297PubMedCrossRef
14.
go back to reference Hansen BP, Beck CL, Beck EP et al (2007) Postarthoroscopic glenohumeral chondrolysis. Am J Sports Med 35:1628–1634PubMedCrossRef Hansen BP, Beck CL, Beck EP et al (2007) Postarthoroscopic glenohumeral chondrolysis. Am J Sports Med 35:1628–1634PubMedCrossRef
15.
go back to reference Karpie JC, Chu CR (2007) Lidocaine exhibits dose- and time- dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med 35:1621–1627PubMedCrossRef Karpie JC, Chu CR (2007) Lidocaine exhibits dose- and time- dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med 35:1621–1627PubMedCrossRef
16.
go back to reference Kellner K, Liebsch G, Klimant I et al (2002) Determination of oxygen gradients in engineered tissue using a fluorescent sensor. Biotechnol Bioeng 80:73–83PubMedCrossRef Kellner K, Liebsch G, Klimant I et al (2002) Determination of oxygen gradients in engineered tissue using a fluorescent sensor. Biotechnol Bioeng 80:73–83PubMedCrossRef
17.
go back to reference Kobayashi S, Meir A, Urban J (2008) The effect of cell density on the rate of glycosaminoglycan accumulation by disc and cartilage cells in vitro. J Orthop Res 26:493–503PubMedCrossRef Kobayashi S, Meir A, Urban J (2008) The effect of cell density on the rate of glycosaminoglycan accumulation by disc and cartilage cells in vitro. J Orthop Res 26:493–503PubMedCrossRef
18.
go back to reference Lee RB, Urban JP (1997) Evidence for a negative Pasteur effect in articular cartilage. Biochem J 321:95–102PubMed Lee RB, Urban JP (1997) Evidence for a negative Pasteur effect in articular cartilage. Biochem J 321:95–102PubMed
19.
go back to reference Lo IK, Sciore P, Chung M et al (2009) Local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner. Arthroscopy 25:707–715PubMedCrossRef Lo IK, Sciore P, Chung M et al (2009) Local anesthetics induce chondrocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner. Arthroscopy 25:707–715PubMedCrossRef
20.
go back to reference Malda J, Rouwkema J, Martens DE et al (2004) Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: measurement and modeling. Biotechnol Bioeng 86:9–18PubMedCrossRef Malda J, Rouwkema J, Martens DE et al (2004) Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: measurement and modeling. Biotechnol Bioeng 86:9–18PubMedCrossRef
21.
go back to reference Manjo G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3–15 Manjo G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3–15
22.
go back to reference McArthur SD, Gardner DL (1992) Articular cartilage fibrillation and permeability to light green SF dye. A method for the detection of pre-microscopic disease? J Bone Joint Surg 74B:668–672 McArthur SD, Gardner DL (1992) Articular cartilage fibrillation and permeability to light green SF dye. A method for the detection of pre-microscopic disease? J Bone Joint Surg 74B:668–672
23.
go back to reference McCarty DJ (1979) Synovial fluid. In: McCarty DJ (ed) Arthritis and allied conditions. Lea and Febiger, Philadelphia, pp 51–69 McCarty DJ (1979) Synovial fluid. In: McCarty DJ (ed) Arthritis and allied conditions. Lea and Febiger, Philadelphia, pp 51–69
24.
go back to reference Negoro K, Kobayashi S, Taneno K et al (2008) Effect of osmolarity on glycosaminoglycan production and cell metabolism of articular chondrocyte under three dimensional culture system. Clin Exp Rheumatol 26:527–533 Negoro K, Kobayashi S, Taneno K et al (2008) Effect of osmolarity on glycosaminoglycan production and cell metabolism of articular chondrocyte under three dimensional culture system. Clin Exp Rheumatol 26:527–533
25.
go back to reference Obradovic B, Meldon JH, Freed LE et al (2000) Glycosaminoglycan deposition in engineered cartilage: experiments and mathematical model. AIChE J 46:1860–1871CrossRef Obradovic B, Meldon JH, Freed LE et al (2000) Glycosaminoglycan deposition in engineered cartilage: experiments and mathematical model. AIChE J 46:1860–1871CrossRef
26.
27.
go back to reference Petty DH, Jazrawi LM, Estrada LS et al (2004) Glenohumeral chondrolysis after shoulder arthotoscopy: case reports and review of the literature. Am J Sports Med 32:509–515PubMedCrossRef Petty DH, Jazrawi LM, Estrada LS et al (2004) Glenohumeral chondrolysis after shoulder arthotoscopy: case reports and review of the literature. Am J Sports Med 32:509–515PubMedCrossRef
28.
go back to reference Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg 90A:986–991CrossRef Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg 90A:986–991CrossRef
29.
go back to reference Radwan IA, Saito S, Goto F (2002) The neurotoxicity of local anesthetics on growing neurons: a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg 94:319–324PubMed Radwan IA, Saito S, Goto F (2002) The neurotoxicity of local anesthetics on growing neurons: a comparative study of lidocaine, bupivacaine, mepivacaine, and ropivacaine. Anesth Analg 94:319–324PubMed
30.
go back to reference Roughley PJ (2004) Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 29:2691–2699PubMedCrossRef Roughley PJ (2004) Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 29:2691–2699PubMedCrossRef
31.
go back to reference Saini S, Wick TM (2003) Concentric cylinder bioreactor for production of tissue engineered cartilage: effect of seeding density and hydrodynamic loading on construct development. Biotechnol Prog 19:510–521PubMedCrossRef Saini S, Wick TM (2003) Concentric cylinder bioreactor for production of tissue engineered cartilage: effect of seeding density and hydrodynamic loading on construct development. Biotechnol Prog 19:510–521PubMedCrossRef
32.
go back to reference Sanders TG, Zlatkin MB, Paruchuri BN et al (2007) Chondrolysis of the glenohumeral joint after arthroscopy: findings on radiography and low-field-strength MRI. AJR Am J Roentgenol 188:1094–1098PubMedCrossRef Sanders TG, Zlatkin MB, Paruchuri BN et al (2007) Chondrolysis of the glenohumeral joint after arthroscopy: findings on radiography and low-field-strength MRI. AJR Am J Roentgenol 188:1094–1098PubMedCrossRef
33.
34.
go back to reference Seshadri V, Coyle CH, Chu CR (2009) Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy 25:337–347PubMedCrossRef Seshadri V, Coyle CH, Chu CR (2009) Lidocaine potentiates the chondrotoxicity of methylprednisolone. Arthroscopy 25:337–347PubMedCrossRef
35.
go back to reference Stockwell RA (1991) Cartilage failure in osteoarthritis: relevance of normal structure and function. Clin Anat 4:161–191CrossRef Stockwell RA (1991) Cartilage failure in osteoarthritis: relevance of normal structure and function. Clin Anat 4:161–191CrossRef
36.
go back to reference Todhunter RJ, Fubini SL, Wootton JA et al (1996) Effect of methylpredonisolone acetate on proteoglycan and collagen metabolism of articular cartilage explants. J Rheumatol 23:1207–1213PubMed Todhunter RJ, Fubini SL, Wootton JA et al (1996) Effect of methylpredonisolone acetate on proteoglycan and collagen metabolism of articular cartilage explants. J Rheumatol 23:1207–1213PubMed
37.
go back to reference Urban JP (1994) The chondrocyte: a cell under pressure. Rheumatology 33:901–908CrossRef Urban JP (1994) The chondrocyte: a cell under pressure. Rheumatology 33:901–908CrossRef
38.
go back to reference Venn M, Maroudas A (1977) Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. chemical composition. Ann Rheum 36:121–129CrossRef Venn M, Maroudas A (1977) Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. chemical composition. Ann Rheum 36:121–129CrossRef
39.
go back to reference Verzijl N, DeGroot J, Thorpe SR et al (2000) Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 275:39027–39031PubMedCrossRef Verzijl N, DeGroot J, Thorpe SR et al (2000) Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 275:39027–39031PubMedCrossRef
40.
go back to reference Wilkins RJ, Hall AC (1995) Control of matrix synthesis in isolated bovine chondrocytes by extracellular and intracellular pH. J Cell Physiol 164:474–481PubMedCrossRef Wilkins RJ, Hall AC (1995) Control of matrix synthesis in isolated bovine chondrocytes by extracellular and intracellular pH. J Cell Physiol 164:474–481PubMedCrossRef
41.
go back to reference Williams GM, Klein TJ, Sah RL (2005) Cell density alters matrix accumulation in two distinct fractions and the mechanical integrity of alginate-chondrocyte constructs. Acta Biomater 1:625–633PubMedCrossRef Williams GM, Klein TJ, Sah RL (2005) Cell density alters matrix accumulation in two distinct fractions and the mechanical integrity of alginate-chondrocyte constructs. Acta Biomater 1:625–633PubMedCrossRef
42.
go back to reference Ysart GE, Mason RM (1994) Responses of articular cartilage explant cultures to different oxygen tensions. Biochim Biophys Acta 1221:15–20PubMedCrossRef Ysart GE, Mason RM (1994) Responses of articular cartilage explant cultures to different oxygen tensions. Biochim Biophys Acta 1221:15–20PubMedCrossRef
Metadata
Title
Lidocaine cytotoxicity to the bovine articular chondrocytes in vitro: changes in cell viability and proteoglycan metabolism
Authors
Tsuyoshi Miyazaki
Shigeru Kobayashi
Kenichi Takeno
Takafumi Yayama
Adam Meir
Hisatoshi Baba
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 7/2011
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-010-1369-9

Other articles of this Issue 7/2011

Knee Surgery, Sports Traumatology, Arthroscopy 7/2011 Go to the issue