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Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy 12/2011

01.12.2011 | Experimental Study

Bupivacaine, ropivacaine, and morphine: comparison of toxicity on human hamstring-derived stem/progenitor cells

verfasst von: Florian Haasters, Hans Polzer, Wolf Christian Prall, Maximilian Michael Saller, Julia Kohler, Stefan Grote, Wolf Mutschler, Denitsa Docheva, Matthias Schieker

Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy | Ausgabe 12/2011

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Abstract

Purpose

Bupivacaine, ropivacaine, and morphine are commonly administered intraarticularly after anterior cruciate ligament (ACL) reconstruction. However, their effects on human tendon stem/progenitor cells (TSPC) have not been studied. Therefore, this study investigates the cytotoxicity of these analgetics on TSPC.

Methods

Cells were isolated from human hamstring grafts of 3 female (age 15, 16 and 59) and 2 male patients (age 16 and 47). Cells were incubated using 0.5% bupivacaine, 0.5/0.75% ropivacaine, and 0.025% morphine. Cell viability was assessed after 0.5, 2, and 6 h using live/dead assay. Metabolic activity and apoptosis were measured by WST- and Annexin-V-FACS-assay after 2 h.

Results

Cell viability remained unchanged after 0.5 h in all groups, while treatment with bupivacaine and 0.5/0.75% ropivacaine resulted in a complete cell loss after 6 h. Contrarily, morphine showed no cytotoxic effect. Cell viability and metabolism were significantly reduced after treatment with bupivacaine (22.1; 8.3%) and 0.75% ropivacaine (56.5; 23.8%), while 0.5% ropivacaine and morphine showed no significant difference compared with controls. Apoptosis was significantly induced after incubation with bupivacaine (58.1%) and 0.75% ropivacaine (26.2%), whereas 0.5% ropivacaine only led to a slight induction compared with morphine and controls.

Conclusions

Clinically administered concentrations of bupivacaine (0.5%) and ropivacaine (0.75%) have a significant cytotoxic effect on human TSPC in vitro, while ropivacaine in a concentration of 0.5% has a mild but not significant effect on apoptosis and cell metabolism. In contrast, morphine does not affect cell survival, metabolism, or apoptosis. Knowing that morphine provides comparable to even prolonged pain reduction after ACL reconstruction, the presented in vitro study suggests morphine as a potentially less toxic analgetic drug for intraarticular application in clinical practice.
Literatur
1.
Zurück zum Zitat Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227PubMedCrossRef Bi Y, Ehirchiou D, Kilts TM, Inkson CA, Embree MC, Sonoyama W, Li L, Leet AI, Seo BM, Zhang L, Shi S, Young MF (2007) Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nat Med 13:1219–1227PubMedCrossRef
2.
Zurück zum Zitat Brandsson S, Karlsson J, Morberg P, Rydgren B, Eriksson BI, Hedner T (2000) Intraarticular morphine after arthroscopic ACL reconstruction: a double-blind placebo-controlled study of 40 patients. Acta Orthop Scand 71:280–285PubMedCrossRef Brandsson S, Karlsson J, Morberg P, Rydgren B, Eriksson BI, Hedner T (2000) Intraarticular morphine after arthroscopic ACL reconstruction: a double-blind placebo-controlled study of 40 patients. Acta Orthop Scand 71:280–285PubMedCrossRef
3.
Zurück zum Zitat Bullough R, Finnigan T, Kay A, Maffulli N, Forsyth NR (2008) Tendon repair through stem cell intervention: cellular and molecular approaches. Disabil Rehabil 30:1746–1751PubMedCrossRef Bullough R, Finnigan T, Kay A, Maffulli N, Forsyth NR (2008) Tendon repair through stem cell intervention: cellular and molecular approaches. Disabil Rehabil 30:1746–1751PubMedCrossRef
4.
Zurück zum Zitat Chu CR, Izzo NJ, Coyle CH, Papas NE, Logar A (2008) The in vitro effects of bupivacaine on articular chondrocytes. J Bone Joint Surg Br 90:814–820PubMedCrossRef Chu CR, Izzo NJ, Coyle CH, Papas NE, Logar A (2008) The in vitro effects of bupivacaine on articular chondrocytes. J Bone Joint Surg Br 90:814–820PubMedCrossRef
5.
Zurück zum Zitat Chu CR, Izzo NJ, Papas NE, Fu FH (2006) In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy 22:693–699PubMedCrossRef Chu CR, Izzo NJ, Papas NE, Fu FH (2006) In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy 22:693–699PubMedCrossRef
6.
Zurück zum Zitat Convery PN, Milligan KR, Quinn P, Sjovall J, Gustafsson U (2001) Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint. Br J Anaesth 87:570–576PubMedCrossRef Convery PN, Milligan KR, Quinn P, Sjovall J, Gustafsson U (2001) Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint. Br J Anaesth 87:570–576PubMedCrossRef
7.
Zurück zum Zitat Dogan N, Erdem AF, Erman Z, Kizilkaya M (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, Kizilkaya M (2004) The effects of bupivacaine and neostigmine on articular cartilage and synovium in the rabbit knee joint. J Int Med Res 32:513–519PubMed
8.
Zurück zum Zitat Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRef Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRef
9.
Zurück zum Zitat Ekdahl M, Wang JH, Ronga M, Fu FH (2008) Graft healing in anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 16:935–947PubMedCrossRef Ekdahl M, Wang JH, Ronga M, Fu FH (2008) Graft healing in anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 16:935–947PubMedCrossRef
10.
Zurück zum Zitat Feinstein DL, Murphy P, Sharp A, Galea E, Gavrilyuk V, Weinberg G (2001) Local anesthetics potentiate nitric oxide synthase type 2 expression in rat glial cells. J Neurosurg Anesthesiol 13:99–105PubMedCrossRef Feinstein DL, Murphy P, Sharp A, Galea E, Gavrilyuk V, Weinberg G (2001) Local anesthetics potentiate nitric oxide synthase type 2 expression in rat glial cells. J Neurosurg Anesthesiol 13:99–105PubMedCrossRef
11.
Zurück zum Zitat Fuson RL, Sherman M, Van Vleet J, Wendt T (1997) The conduct of orthopaedic clinical trials. J Bone Joint Surg Am 79:1089–1098PubMed Fuson RL, Sherman M, Van Vleet J, Wendt T (1997) The conduct of orthopaedic clinical trials. J Bone Joint Surg Am 79:1089–1098PubMed
12.
Zurück zum Zitat Gupta A, Bodin L, Holmstrom B, Berggren L (2001) A systematic review of the peripheral analgesic effects of intraarticular morphine. Anesth Analg 93:761–770PubMedCrossRef Gupta A, Bodin L, Holmstrom B, Berggren L (2001) A systematic review of the peripheral analgesic effects of intraarticular morphine. Anesth Analg 93:761–770PubMedCrossRef
13.
Zurück zum Zitat Jaureguito JW, Wilcox JF, Cohn SJ, Thisted RA, Reider B (1995) A comparison of intraarticular morphine and bupivacaine for pain control after outpatient knee arthroscopy. A prospective, randomized, double-blinded study. Am J Sports Med 23:350–353PubMedCrossRef Jaureguito JW, Wilcox JF, Cohn SJ, Thisted RA, Reider B (1995) A comparison of intraarticular morphine and bupivacaine for pain control after outpatient knee arthroscopy. A prospective, randomized, double-blinded study. Am J Sports Med 23:350–353PubMedCrossRef
14.
Zurück zum Zitat Jaureguito JW, Wilcox JF, Thisted RA, Phillips C, Cunningham B, Reider B (2002) The effects of morphine on human articular cartilage of the knee: an in vitro study. Arthroscopy 18:631–636PubMedCrossRef Jaureguito JW, Wilcox JF, Thisted RA, Phillips C, Cunningham B, Reider B (2002) The effects of morphine on human articular cartilage of the knee: an in vitro study. Arthroscopy 18:631–636PubMedCrossRef
15.
Zurück zum Zitat Joshi GP, McCarroll SM, Brady OH, Hurson BJ, Walsh G (1993) Intra-articular morphine for pain relief after anterior cruciate ligament repair. Br J Anaesth 70:87–88PubMedCrossRef Joshi GP, McCarroll SM, Brady OH, Hurson BJ, Walsh G (1993) Intra-articular morphine for pain relief after anterior cruciate ligament repair. Br J Anaesth 70:87–88PubMedCrossRef
16.
Zurück zum Zitat Joshi GP, McCarroll SM, O’Brien TM, Lenane P (1993) Intraarticular analgesia following knee arthroscopy. Anesth Analg 76:333–336PubMed Joshi GP, McCarroll SM, O’Brien TM, Lenane P (1993) Intraarticular analgesia following knee arthroscopy. Anesth Analg 76:333–336PubMed
17.
Zurück zum Zitat Karlsson J, Rydgren B, Eriksson B, Jarvholm U, Lundin O, Sward L, Hedner T (1995) Postoperative analgesic effects of intra-articular bupivacaine and morphine after arthroscopic cruciate ligament surgery. Knee Surg Sports Traumatol Arthrosc 3:55–59PubMedCrossRef Karlsson J, Rydgren B, Eriksson B, Jarvholm U, Lundin O, Sward L, Hedner T (1995) Postoperative analgesic effects of intra-articular bupivacaine and morphine after arthroscopic cruciate ligament surgery. Knee Surg Sports Traumatol Arthrosc 3:55–59PubMedCrossRef
18.
Zurück zum Zitat Lim JK, Hui J, Li L, Thambyah A, Goh J, Lee EH (2004) Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy 20:899–910PubMedCrossRef Lim JK, Hui J, Li L, Thambyah A, Goh J, Lee EH (2004) Enhancement of tendon graft osteointegration using mesenchymal stem cells in a rabbit model of anterior cruciate ligament reconstruction. Arthroscopy 20:899–910PubMedCrossRef
19.
Zurück zum Zitat Marret E, Gentili M, Bonnet MP, Bonnet F (2005) Intra-articular ropivacaine 0.75% and bupivacaine 0.50% for analgesia after arthroscopic knee surgery: a randomized prospective study. Arthroscopy 21:313–316PubMedCrossRef Marret E, Gentili M, Bonnet MP, Bonnet F (2005) Intra-articular ropivacaine 0.75% and bupivacaine 0.50% for analgesia after arthroscopic knee surgery: a randomized prospective study. Arthroscopy 21:313–316PubMedCrossRef
20.
Zurück zum Zitat Møiniche S, Mikkelsen S, Wetterslev J, Dahl JB (1999) A systematic review of intra-articular local anesthesia for postoperative pain relief after arthroscopic knee surgery. Reg Anesth Pain Med 24:430–437PubMed Møiniche S, Mikkelsen S, Wetterslev J, Dahl JB (1999) A systematic review of intra-articular local anesthesia for postoperative pain relief after arthroscopic knee surgery. Reg Anesth Pain Med 24:430–437PubMed
21.
Zurück zum Zitat Müller M, Burkhardt J, Borchardt E, Buttner-Janz K (2001) Postoperative analgesic effect after intra-articular morphine or ropivacaine following knee arthroscopy - a prospective randomized, doubleblinded study. Schmerz 15:3–9PubMedCrossRef Müller M, Burkhardt J, Borchardt E, Buttner-Janz K (2001) Postoperative analgesic effect after intra-articular morphine or ropivacaine following knee arthroscopy - a prospective randomized, doubleblinded study. Schmerz 15:3–9PubMedCrossRef
22.
Zurück zum Zitat Nouette-Gaulain K, Dadure C, Morau D, Pertuiset C, Galbes O, Hayot M, Mercier J, Sztark F, Rossignol R, Capdevila X (2009) Age-dependent bupivacaine-induced muscle toxicity during continuous peripheral nerve block in rats. Anesthesiology 111:1120–1127PubMedCrossRef Nouette-Gaulain K, Dadure C, Morau D, Pertuiset C, Galbes O, Hayot M, Mercier J, Sztark F, Rossignol R, Capdevila X (2009) Age-dependent bupivacaine-induced muscle toxicity during continuous peripheral nerve block in rats. Anesthesiology 111:1120–1127PubMedCrossRef
23.
Zurück zum Zitat Ouyang HW, Goh JC, Lee EH (2004) Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model. Am J Sports Med 32:321–327PubMedCrossRef Ouyang HW, Goh JC, Lee EH (2004) Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model. Am J Sports Med 32:321–327PubMedCrossRef
24.
Zurück zum Zitat Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am 90:986–991PubMedCrossRef Piper SL, Kim HT (2008) Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am 90:986–991PubMedCrossRef
25.
Zurück zum Zitat Soon MY, Hassan A, Hui JH, Goh JC, Lee EH (2007) An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model: a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration. Am J Sports Med 35:962–971PubMedCrossRef Soon MY, Hassan A, Hui JH, Goh JC, Lee EH (2007) An analysis of soft tissue allograft anterior cruciate ligament reconstruction in a rabbit model: a short-term study of the use of mesenchymal stem cells to enhance tendon osteointegration. Am J Sports Med 35:962–971PubMedCrossRef
26.
Zurück zum Zitat Stein C, Comisel K, Haimerl E, Yassouridis A, Lehrberger K, Herz A, Peter K (1991) Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med 325:1123–1126PubMedCrossRef Stein C, Comisel K, Haimerl E, Yassouridis A, Lehrberger K, Herz A, Peter K (1991) Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med 325:1123–1126PubMedCrossRef
27.
Zurück zum Zitat Vintar N, Rawal N, Veselko M (2005) Intraarticular patient-controlled regional anesthesia after arthroscopically assisted anterior cruciate ligament reconstruction: ropivacaine/morphine/ketorolac versus ropivacaine/morphine. Anesth Analg 101:573–578 (table) Vintar N, Rawal N, Veselko M (2005) Intraarticular patient-controlled regional anesthesia after arthroscopically assisted anterior cruciate ligament reconstruction: ropivacaine/morphine/ketorolac versus ropivacaine/morphine. Anesth Analg 101:573–578 (table)
28.
Zurück zum Zitat Volkmer E, Drosse I, Otto S, Stangelmayer A, Stengele M, Kallukalam BC, Mutschler W, Schieker M (2008) Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone. Tissue Eng Part A 14:1331–1340PubMedCrossRef Volkmer E, Drosse I, Otto S, Stangelmayer A, Stengele M, Kallukalam BC, Mutschler W, Schieker M (2008) Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone. Tissue Eng Part A 14:1331–1340PubMedCrossRef
29.
Zurück zum Zitat Werdehausen R, Fazeli S, Braun S, Hermanns H, Essmann F, Hollmann MW, Bauer I, Stevens MF (2009) Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. Br J Anaesth 103:711–718PubMedCrossRef Werdehausen R, Fazeli S, Braun S, Hermanns H, Essmann F, Hollmann MW, Bauer I, Stevens MF (2009) Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. Br J Anaesth 103:711–718PubMedCrossRef
Metadaten
Titel
Bupivacaine, ropivacaine, and morphine: comparison of toxicity on human hamstring-derived stem/progenitor cells
verfasst von
Florian Haasters
Hans Polzer
Wolf Christian Prall
Maximilian Michael Saller
Julia Kohler
Stefan Grote
Wolf Mutschler
Denitsa Docheva
Matthias Schieker
Publikationsdatum
01.12.2011
Verlag
Springer-Verlag
Erschienen in
Knee Surgery, Sports Traumatology, Arthroscopy / Ausgabe 12/2011
Print ISSN: 0942-2056
Elektronische ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-011-1564-3

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