Department of Orthopaedic Surgery, University of California-San Francisco, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
J Bone Joint Surg Am. 2013 Jan 16;95(2):132-7. doi: 10.2106/JBJS.K.01291.
Local anesthetics are frequently delivered intra-articularly to provide perioperative pain control. Previous studies have shown that the commonly used drugs lidocaine, ropivacaine, and bupivacaine can be toxic to human chondrocytes. The present study was conducted to determine whether the toxic effects of local anesthetics on human chondrocytes also extend to human mesenchymal stem cells.
Human mesenchymal stem cells from three healthy donors were grown in tissue culture and exposed to the following anesthetic treatments for sixty minutes: (1) 1% lidocaine, (2) 2% lidocaine, (3) 0.25% bupivacaine, (4) 0.5% bupivacaine, (5) 0.2% ropivacaine, and (6) 0.5% ropivacaine. The cells were then allowed to recover for twenty-four hours in regular growth media, and viability was measured with use of fluorescent staining for live cells or a luminescence assay for ATP content.
The live cell counts and ATP content were correlated (r2 = 0.79), and 2% lidocaine was found to be significantly more toxic than all doses of bupivacaine and ropivacaine. Treatment with 1% lidocaine resulted in significantly fewer live cells (49%) compared with the control, and the live cell count was also significantly less than that for the other anesthetics. However, the ATP level in the 1% lidocaine group was not significantly lower than those in the other groups. Bupivacaine and ropivacaine did not exhibit significant differences in toxicity compared with the control or with each other.
Ropivacaine and bupivacaine had limited toxicity in human mesenchymal stem cells. However, lidocaine could significantly decrease mesenchymal stem cell viability. Since other studies have shown ropivacaine to be less toxic to chondrocytes than bupivacaine, ropivacaine may be a safer intra-articular anesthetic.
Mesenchymal stem cells likely play a key role in healing following surgical procedures such as microfracture and ligament reconstruction. If local anesthetics are used following joint surgery, selection of an agent with low toxicity toward mesenchymal stem cells, such as ropivacaine, may maximize tissue healing potential.
局部麻醉药常被关节内给药以提供围手术期疼痛控制。先前的研究表明,常用药物利多卡因、罗哌卡因和布比卡因可对人软骨细胞产生毒性。本研究旨在确定局部麻醉药对人软骨细胞的毒性作用是否也延伸至人骨髓间充质干细胞。
从 3 名健康供体中培养人骨髓间充质干细胞,并将其暴露于以下麻醉处理 60 分钟:(1)1%利多卡因,(2)2%利多卡因,(3)0.25%布比卡因,(4)0.5%布比卡因,(5)0.2%罗哌卡因,和(6)0.5%罗哌卡因。然后,将细胞在常规生长培养基中恢复 24 小时,并使用荧光染色法检测活细胞或发光法检测 ATP 含量来测量细胞活力。
活细胞计数和 ATP 含量呈相关性(r2=0.79),并且 2%利多卡因被发现比所有布比卡因和罗哌卡因剂量都更具毒性。1%利多卡因处理导致活细胞数量明显减少(49%),与对照组相比,活细胞计数也明显少于其他麻醉剂。然而,1%利多卡因组的 ATP 水平与其他组无显著差异。与对照组或彼此相比,布比卡因和罗哌卡因的毒性没有显著差异。
罗哌卡因和布比卡因对人骨髓间充质干细胞的毒性有限。然而,利多卡因可显著降低间充质干细胞的活力。由于其他研究表明罗哌卡因对软骨细胞的毒性小于布比卡因,因此罗哌卡因可能是一种更安全的关节内麻醉剂。
骨髓间充质干细胞可能在微骨折和韧带重建等手术程序后的愈合中发挥关键作用。如果在关节手术后使用局部麻醉剂,选择对间充质干细胞毒性较低的药物,如罗哌卡因,可能最大限度地提高组织愈合潜力。