The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint

Osman Çevik; Özlem Öz Gergin; Karamehmet Yildiz; Adnan Bayram; Özlem Canöz; Mehmet Halici; Münevver Baran; Arzu Yay; Sait Polat

doi:10.1016/j.bjane.2018.06.008

Scientific Article

The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint

Os efeitos condrotóxicos e apoptóticos de levobupivacaína e bupivacaína na articulação do joelho de coelhos

Osman Çevik; Özlem Öz Gergin; Karamehmet Yildiz; Adnan Bayram; Özlem Canöz; Mehmet Halici; Münevver Baran; Arzu Yay; Sait Polat

http://dx.doi.org/10.1016/j.bjane.2018.06.008 Braz J Anesthesiol, vol.68, n6, p.605-612, 2018

PDF

Downloads: 0

Abstract

Abstract Background: A single dose injection or continuous infusion of local anesthetics into the joint space is considered to be a well-defined analgesia technique. The aim of this study was to investigate the chondrotoxic and apoptotic effects of single-dose intra-articular injection of levobupivacaine and bupivacaine on rabbit knee joint tissues. Materials and methods: The animals were allocated into two groups each containing 20 rabbits. 0.5% levobupivacaine (Group L) and 0.5% bupivacaine (Group B) were applied intra-articularly to the left posterior joints of rabbits. At the same time, normal saline was applied to the right posterior leg knee joints of rabbits in both groups and used as a control (Group S). At the end of the 7th and 28th days after the intraarticular injections, ten randomly chosen rabbits in each group were killed by applying intraperitoneal thiopental. Sections of cartilage tissue samples were stained for light microscopic examinations and the TUNEL method was used to investigate apoptotic cells. Results: As a result of immunofluorescence microscopic examination, the number of apoptotic cells in Group B at day 7 and day 28 were both significantly higher than Group L and S (p < 0.05). Also, the number of apoptotic cells in Group L at day 7 and day 28 were both significantly higher than Group S (p < 0.05). Conclusions: We found that bupivacaine is more chondrotoxic than other anesthetic agent and increases the number of apoptotic cells. These results indicated that bupivacaine caused high chondrotoxic damage and it led to more apoptotic activation than levobupivacaine.

Keywords

Apoptosis, Bupivacaine, Chondrotoxicity, Levobupivacaine, Local anesthetic

Resumo

Resumo Justificativa: Uma injeção em dose única ou infusão contínua de anestésicos locais no espaço articular é considerada uma técnica de analgesia bem definida. O objetivo deste estudo foi investigar os efeitos condrotóxicos e apoptóticos da injeção intra-articular com dose única de levobupivacaína e bupivacaína em tecidos articulares do joelho de coelho. Material e métodos: Os animais foram alocados em dois grupos, cada um contendo 20 coelhos. Levobupivacaína a 0,5% (Grupo L) e bupivacaína a 0,5% (Grupo B) foram aplicadas intra-articularmente nas articulações posteriores esquerdas de coelhos. Ao mesmo tempo, solução salina normal foi aplicada nas articulações do joelho da perna posterior direita de coelhos em ambos os grupos e usada como controle (Grupo S). Ao fim do 7° e 28° dias após as injeções intra-articulares, 10 coelhos escolhidos aleatoriamente em cada grupo foram mortos por aplicação de tiopental intraperitoneal. Seções de amostras de tecido cartilaginoso foram coradas para exames de microscopia de luz, e o método TUNEL foi usado para investigar células apoptóticas. Resultados: Como resultado do exame microscópico de imunofluorescência nos dias 7 e 28, o número de células apoptóticas no Grupo B foi significativamente maior que nos grupos L e S (p < 0,05). Além disso, o número de células apoptóticas nos dias 7 e 28 foi significativamente maior no Grupo L do que no Grupo S (p < 0,05). Conclusões: Demonstramos que a bupivacaína é mais condrotóxica do que o outro agente anestésico e aumenta o número de células apoptóticas. Esses resultados indicaram que a bupivacaína causou intensa lesão condrotóxica e levou a uma ativação apoptótica maior do que a levobupivacaína.

Palavras-chave

Apoptose, Bupivacaína, Condrotoxicidade, Levobupivacaína, Anestésico local

References

Zeidan A, Kassem R, Nahleh N. Intraarticular tramadol bupivacaine combination prolongs the duration of postoperative analgesia after outpatient arthroscopic knee surgery. Anesth Analg. 2008;107:292-9.

Fester EW, Noyes FR. Postoperative chondrolysis of the knee: 3 case reports and a review of the literature. Am J Sports Med. 2009;37:1848-54.

Chu CR, Izzo NJ, Coyle CH. The in vitro effects of bupivacaine on articular chondrocytes. J Bone Jt Surg Br. 2008;90:814-20.

Casati A, Putzu M. Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?. Best Pract Res Clin Anaesthesiol. 2005;19:247-68.

Zink W, Seif C, Bohl JRE. The acute myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blockades. Anesth Analg. 2003;97:1173-9.

Park CJ, Park SA, Yoon TG. Bupivacaine induces apoptosis via ROS in the Schwann cell line. J Dent Res. 2005;84:852-7.

Borazan M, Karalezli A, Oto S. Induction of apoptosis of rabbit corneal endothelial cells by preservative-free lidocaine hydrochloride 2%, ropivacaine 1%, or levobupivacaine 0.75%. J Cataract Refract Surg. 2009;35:753-8.

Grishko V, Xu M, Wilson G. Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine. J Bone Joint Surg Am. 2010;92:609-18.

Beyzadeoğlu T, Torun Köse G, Ekinci ID. Cytotoxicity of local anesthetics to rats' articular cartilage: an experimental study. Acta Orthop Traumatol Turc. 2012;46:201-7.

Natori S, Selzner M, Valentino KL. Apoptosis of sinusoidal endothelial cells occurs during liver preservation injury by a caspase-dependent mechanism. Transplantation. 1999;68:89-96.

Gomoll AH, Kang RW, Williams JM. Chondrolysis after continuous intra-articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder. Arthroscopy. 2006;22:813-9.

Dragoo JL, Korotkova T, Kanwar R. The effect of local anesthetic administered via pain pump on chondrocyte viability. Am J Sports Med. 2008;36:1484-8.

Chu CR, Izzo NJ, Papas NE. In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy. 2006;22:693-9.

Nouette-Gaulain K, Sirvent P, Canal-Raffin M. Effects of intermittent femoral nerve injections of bupivacaine, levobupivacaine and ropivacaine on mitochondrial energy metabolism and intracellular calcium homeostasis in rat psoas muscle. Anesthesiology. 2007;106:1026-34.

Boselli E, Duflo F, Debon R. The induction of apoptosis by local anesthetics: a comparison between lidocaine and ropivacaine. Anesth Analg. 2003;96:755-6.

Unami A, Shinohara Y, Ichikawa T. Biochemical and microarray analyses of bupivacaine induced apoptosis. J Toxicol Sci. 2003;28:77-94.

Lee HT, Xu H, Siegel CD. Local anesthetics induce human renal cell apoptosis. Am J Nephrol. 2003;23:129-39.

Doğan N, Erdem AF, Erman Z. The effects of bupivacaine and neostigmine on articular cartilage and synovium in the rabbit knee joint. J Int Med Res. 2004;32:513-9.

Kuwata K, Sato S, Era S. Cross relaxation times of normal and biochemically induced osteoarthritic rabbit knee cartilages. Jpn J Physiol. 1997;47:291-7.

Kockx MM, Muhring J, Knaapen MW. RNA synthesis and splicing interferes with DNA in situ end labeling techniques used to detect apoptosis. Am J Pathol. 1998;152:885-8.

Mountz JD, Zhou T. Apoptosis and autoimmunity. A textbook of rheumatology: arthritis and allied conditions. 2001.

Amaniti E, Drampa F, Kouzi-Koliakos K. Ropivacaine myotoxicity after single intramuscular injection in rats. Eur J Anesth. 2006;23:130-5.

Stahelin BJ, Marti U, Solioz M. False positive staining in the TUNEL assay to detect apoptosis in liver and intestine is caused by endogenous nucleases and inhibited by diethylpyrocarbonate. Mol Pathol. 1998;51:204-8.

Webb ST, Ghosh S. Intraarticular bupivacaine: potentially chondrotoxic?. Br J Anaesth. 2009;102:439-41.

Fulkerson JP, Damiano P. Effect of prostaglandin E2 on adult pig articular cartilage slices in culture. Clin Orthop Relat Res. 1983;179:266-9.

Gomoll AH, Yanke AB, Kang RW. Long-term effects of bupivacaine on cartilage in a rabbit shoulder model. Am J Sports Med. 2009;37:72-7.

The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint

Os efeitos condrotóxicos e apoptóticos de levobupivacaína e bupivacaína na articulação do joelho de coelhos

Osman Çevik; Özlem Öz Gergin; Karamehmet Yildiz; Adnan Bayram; Özlem Canöz; Mehmet Halici; Münevver Baran; Arzu Yay; Sait Polat

Abstract

Keywords

Resumo

Palavras-chave

References

Links

Share

Braz J Anesthesiol