TAHSİN BEYZA BEYZADEOĞLU, Gamze KÖSE TORUN, Işın D. EKİCİ, Halil BEKLER, Cemil YILMAZ

Cytotoxicity of local anesthetics to rats' articular cartilage: an experimental study

Amaç: Çalışmamızın amacı bupivakain, levobupivakain ve tramadolün eklem kıkırdağı ve kondrositler üzerindeki etkisini in vivo ve in vitro olarak deneysel sıçan modelinde araştırmaktı. Çalışma planı: 250-300 g ağırlığında 30 adet Sprague Dawley cinsi sıçan randomize olarak 3 gruba ayrıldı. Bupivakain (Grup 1), levobupivakain (Grup 2) ve tramadol (Grup 3) sağ dizlerine, %0.9 serum fizyolojik ise sol dizlerine enjekte edildi. Her gruptan sıçanların 5’inin yaşamı 48. saatte, 5’inki ise 10. günde sonlandırıldı. Örnekler fikse ve dekalsifiye edilerek, hematoksilen&eosin ve toluidin mavisi ile boyandı. Tüm örnekler ICRS osteoartrit ve kıkırdak histopatolojik sınıflama sistemine göre değerlendirildi. Sıçanların eklem kıkırdak hücreleri kültür edilip hücre kültür kaplarına ekildi. Ekilmiş kıkırdak hücre örnekleri (104 hücre/ml) %0.5’lik üç farklı (sırasıyla bupivakain, levobupivakain ve tramadol) anestezik ajan içinde inkübe edildi. Örneklerdeki hücre sayısını ölçmek için, CellTiter 96® Nonradioactivity Cell Proliferation (MTS) assay kullanıldı. Bulgular: Levobupivakain enjekte edilen grupta, 10. gün yaşamları sonlandırılan sıçanlarda, 48. saatte sonlandırılanlara kıyasla istatistiksel olarak belirgin yüksek OARSI derecesi, OA evresi ve skorları bulundu. (p

Lokal anesteziklerin sıçanların eklem kıkırdağına sitotoksik etkisi: Deneysel çalışma

Objective: The aim of this study was to evaluate the effects of both in vivo and in vitro bupivacaine, levobupivacaine and tramadol on articular cartilage and chondrocytes in experimental rat models. Methods: Thirty mature Sprague Dawley rats weighing 230-300 g were randomized into 3 groups. Bupivacaine (Group 1), levobupivacaine (Group 2) and tramadol (Group 3) were injected into the right knee joints and a physiological 0.9% saline into the left. From each group, 5 rats were executed 48 hours following drug administration after 5 and 10 days. The specimens were fixed, decalcified and stained with hematoxylin & eosin and toluidine blue. All samples were histopathologically evaluated according to the recommendation of ICRS’ osteoarthritis and cartilage histopathology grading and staging system. Articular cartilage cells of the rats were cultured and seeded into cell culture flasks. Cartilage cell seeded samples (104 cells/ml) were incubated in three different anesthetic agents (0.5%); bupivacaine, levobupivacaine, and tramadol, respectively. CellTiter 96® Non-Radioactive Cell Proliferation (MTS) assay was used to determine the cell density on the samples. Results: Statistically significant higher OARSI grades and OA stage and scores were detected when comparing the group injected with levobupivacaine and executed after 10 days with the levobupivacaine injected group killed after 48 hours (p

___

1. Beyzadeoglu T, Yilmaz C, Bekler H, Gokce A, Sayin MM. Intraarticular tramadol plus pericapsular incisional bupivacaine provides better analgesia than intraarticular plus pericapsular incisional bupivacaine after outpatient arthroscopic partial meniscectomy. Knee Surg Sports Traumatol Arthrosc 2007;15:564-8.
2. Goodwin RC, Amjadi F, Parker RD. Short-term analgesic effects of intra-articular injections after knee arthroscopy. Arthroscopy 2005;21:307-12.
3. Kirdemir P, Marsan A, Gogus N, Tabak Y, Tekin M. Comparison between the analgesic effects of intraarticular neostigmine, tramadol and tenoxicam. [Article in Turkish] Acta Orthop Traumatol Turc 2001;35:358-62.
4. Marret E, Gentili M, Bonnet MP, Bonnet F. Intra-articular ropivacaine 0.75% and bupivacaine 0.50% for analgesia after arthroscopic knee surgery: a randomized prospective study. Arthroscopy 2005;21:313-6.
5. Rasmussen S, Lorentzen JS, Larsen AS, Thomsen ST, Kehlet H. Combined intra-articular glucocorticoid, bupivacaine and morphine reduces pain and convalescence after diagnostic knee arthroscopy. Acta Orthop Scand 2002;73: 175-8.
6. Talu GK, Ozyalçin S, Koltka K, Ertürk E, Akinci O, Aflik M, et al. Comparison of efficacy of intraarticular application of tenoxicam, bupivacaine and tenoxicam: bupivacaine combination in arthroscopic knee surgery. Knee Surg Sports Traumatol Arthrosc 2002;10:355-60.
7. Uysalel A, Keçik Y, Kirdemir P, Sayin M, Binnet M. Comparison of intraarticular bupivacaine with the addition of morphine or fentanyl for analgesia after arthroscopic surgery. Arthroscopy 1995;11:660-3.
8. Akinci SB, Saricao¤lu F, Atay OA, Doral MN, Kanbak M. Analgesic effect of intra-articular tramadol compared with morphine after arthroscopic knee surgery. Arthroscopy 2005; 21:1060-5.
9. Allen GC, St Amand MA, Lui AC, Johnson DH, Lindsay MP. Postarthroscopy analgesia with intraarticular bupivacaine/ morphine. A randomized clinical trial. Anesthesiology 1993;79:475-80.
10. Jacobson E, Assareh H, Cannerfelt R, Anderson RE, Jakobsson JG. The postoperative analgesic effects of intraarticular levobupivacaine in elective day-case arthroscopy of the knee: a prospective, randomized, double-blind clinical study. Knee Surg Sports Traumatol Arthrosc 2006;14:120-4.
11. Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 2006;14:13-29.
12. Dogan N, Erdem AF, Erman Z, Kizilkaya M. The effects of bupivacaine and neostigmine on articular cartilage and synovium in the rabbit knee joint. J Int Med Res 2004;32:513-9.
13. Gomoll AH, Kang RW, Williams JM, Bach BR, Cole BJ. Chondrolysis after continuous intra-articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder. Arthroscopy 2006;22:813-9.
14. Gomoll AH, Yanke AB, Kang RW, Chubinskaya S, Williams JM, Bach BR, et al. Long-term effects of bupivacaine on cartilage in a rabbit shoulder model. Am J Sports Med 2009;37:72-7.
15. Chu CR, Izzo NJ, Papas NE, Fu FH. In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy 2006;22:693-9.
16. Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med 2007;35:1628-34.
17. Baker JF, Byrne DP, Walsh PM, Mulhall KJ. Human chondrocyte viability after treatment with local anesthetic and/or magnesium: results from an in vitro study. Arthroscopy 2011; 27:213-7.
18. Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis Rheum 2000;43:1916-26.