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Erschienen 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

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

Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy | Ausgabe 7/2011

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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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Schumacher HR (2003) Aspiration and injection therapies for joints. Arthritis Rheum 49:413–420PubMedCrossRef Schumacher HR (2003) Aspiration and injection therapies for joints. Arthritis Rheum 49:413–420PubMedCrossRef
34.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Lidocaine cytotoxicity to the bovine articular chondrocytes in vitro: changes in cell viability and proteoglycan metabolism
verfasst von
Tsuyoshi Miyazaki
Shigeru Kobayashi
Kenichi Takeno
Takafumi Yayama
Adam Meir
Hisatoshi Baba
Publikationsdatum
01.07.2011
Verlag
Springer-Verlag
Erschienen in
Knee Surgery, Sports Traumatology, Arthroscopy / Ausgabe 7/2011
Print ISSN: 0942-2056
Elektronische ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-010-1369-9

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