Oeyen Anne Lene, Kircher Jörn, Vogl Melanie, Ickert Irina, Osada Nani, Krauspe Rüdiger, Bittersohl Bernd, Herten Monika
Department of Orthopedic and Trauma Surgery, Caritas-Klinik Maria Heimsuchung Berlin-Pankow, Berlin, Germany.
Department of Orthopedic Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Arthrosc Sports Med Rehabil. 2021 Dec 23;4(2):e459-e469. doi: 10.1016/j.asmr.2021.11.004. eCollection 2022 Apr.
The purposes of this in vitro study were to investigate whether the addition of dexamethasone can compensate for any cytotoxic effects of the amide-type local anesthetics (LA) bupivacaine and ropivacaine and whether morphine and morphine-6-glucuronide (M6G) may be a safe alternative for peritendinous application.
Biopsies of human biceps tendons ( = 6) were dissected and cultivated. Cells were characterized by the expression for tenocyte markers, collagen I, biglycan, tenascin C, scleraxis, and RUNX via reverse transcriptase-polymerase chain reaction and immunohistochemistry. Tenocytes were incubated with bupivacaine, ropivacaine, morphine, M6G, or a saline control with and without addition of dexamethasone for 15, 60, or 240 min. Cell viability was determined by quantifying the presence of adenosine-triphosphate.
Significant time-dependent cytotoxic effects were observed for LA after all exposure times. After 15, 60, and 240 minutes, cell viability decreased to 81.1%, 49.4% and 0% ( < .001) for bupivacaine and to 81.4%, 69.6%, and 9.3% ( < .001) for ropivacaine compared to saline control. Dexamethasone did not compensate for these cytotoxic effects. Cell viability was not affected after 15, 60-min exposures to morphine and M6G but decreased significantly ( < .001) after 240 minutes compared to saline control. However, in combination with dexamethasone, tenocyte viability was significantly increased at all times for morphine ( < .01) and at 15 and 60 minutes for M6G ( < .01).
The results showed that amide-type LA have a time-dependent cytotoxic effect on human tenocytes in vitro, which could not be compensated for by dexamethasone, whereas morphine and M6G had no cytotoxic effects on tenocytes after 15 and 60 minutes. The addition of dexamethasone to morphine and M6G had a positive effect on viability, which increased significantly compared to the opioids.
It is known that amide-type local anesthetics used for local joint analgesia have chondrotoxic side-effects. The combined application of morphine and dexamethasone may be a safe alternative.
本体外研究的目的是调查添加地塞米松是否可以补偿酰胺类局部麻醉药布比卡因和罗哌卡因的任何细胞毒性作用，以及吗啡和吗啡 - 6 - 葡萄糖醛酸苷（M6G）是否可能是腱鞘周围应用的安全替代物。
解剖并培养人肱二头肌肌腱活检组织（n = 6）。通过逆转录 - 聚合酶链反应和免疫组织化学，根据肌腱细胞标志物、I型胶原蛋白、双糖链蛋白聚糖、肌腱蛋白C、硬骨素和RUNX的表达对细胞进行表征。将肌腱细胞与布比卡因、罗哌卡因、吗啡、M6G或生理盐水对照一起孵育，添加或不添加地塞米松，孵育15、60或240分钟。通过定量三磷酸腺苷的存在来测定细胞活力。
在所有暴露时间后，均观察到局部麻醉药具有显著的时间依赖性细胞毒性作用。与生理盐水对照相比，在15、60和240分钟后，布比卡因组细胞活力分别降至81.1%、49.4%和0%（P <.001），罗哌卡因组分别降至81.4%、69.6%和9.3%（P <.001）。地塞米松不能补偿这些细胞毒性作用。在15、60分钟暴露于吗啡和M6G后，细胞活力未受影响，但与生理盐水对照相比，240分钟后显著降低（P <.001）。然而，与地塞米松联合使用时，吗啡在所有时间点均显著提高肌腱细胞活力（P <.01），M6G在15和60分钟时显著提高（P <.01）。
结果表明，酰胺类局部麻醉药在体外对人肌腱细胞具有时间依赖性细胞毒性作用，地塞米松不能补偿该作用，而吗啡和M6G在15和60分钟后对肌腱细胞无细胞毒性作用。向吗啡和M6G中添加地塞米松对细胞活力有积极影响，与阿片类药物相比显著提高。
已知用于局部关节镇痛的酰胺类局部麻醉药具有软骨毒性副作用。吗啡和地塞米松联合应用可能是一种安全的替代方法。
