Department of Orthopaedic Surgery and Sports Medicine, Detroit Medical Center, 3990 John R Street, PO Box 137, Detroit, MI 48201, USA.
Ascension Providence Hospital, 16001 W Nine Mile Rd, Southfield, MI 48075, USA.
Knee. 2020 Dec;27(6):1746-1752. doi: 10.1016/j.knee.2020.10.019. Epub 2020 Nov 13.
A multitude of chemical agents are currently used intra-articularly to decrease pain after orthopaedic procedures including total knee arthroplasty. However, the possible deleterious effects of these injectable chemicals on chondrocyte viability have not been weighed against their potential benefits. Using a human osteoarthritic chondrocyte model, the purpose of this study was to assess the potential for cartilage damage caused by bupivacaine, Toradol, Duramorph, and acetaminophen from surgical local anesthesia.
Human distal femur and proximal tibia cross sections were obtained during total knee arthroplasty and divided into control group and experimental groups treated by bupivacaine, Toradol, Duramorph, and acetaminophen respectively. Chondrocytes obtained from enzymatically digested cartilage were cultured using a 3D alginate bead culture method to ensure lower rates of dedifferentiation. Chondrocyte bead cultures were exposed to the study chemicals. The gene expression and chondrocyte viability were measured by RT-PCR and flow cytometry, respectively.
Compared with untreated group bupivacaine treatment led to the greatest cellular apoptosis with 30.5 ± 11% dead cells (P = 0.000). Duramorph and acetaminophen did not result in a significant increase in cell death. Bupivacaine treatment led to an increase in Caspase 3 gene expression (P = 0.000) as well as the acetaminophen treatment (P = 0.001) when compared to control.
Our data demonstrated that Duramorph and Toradol were not cytotoxic to human chondrocytes and may be better alternatives to the frequently used and more cytotoxic bupivacaine. Acetaminophen did not result in increased cell death; however, it did show increased caspase 3 gene expression and caution should be considered.
目前有许多化学药物被用于减少骨科手术后的疼痛，包括全膝关节置换术。然而，这些可注射化学物质对软骨细胞活力的潜在有害影响尚未与其潜在益处进行权衡。本研究使用人骨性关节炎软骨细胞模型，旨在评估布比卡因、托烷司琼、杜冷丁和对乙酰氨基酚这 4 种外科局部麻醉用药物对软骨造成损伤的可能性。
在全膝关节置换术中获得人远端股骨和近端胫骨的横截面，并将其分为对照组和实验组，实验组分别接受布比卡因、托烷司琼、杜冷丁和对乙酰氨基酚治疗。从酶消化的软骨中获得的软骨细胞使用 3D 藻酸盐珠培养方法进行培养，以确保较低的去分化率。将软骨细胞珠暴露于研究用化学物质中。通过 RT-PCR 和流式细胞术分别测量基因表达和软骨细胞活力。
与未处理组相比，布比卡因处理导致细胞凋亡最多，有 30.5 ± 11%的死亡细胞（P = 0.000）。杜冷丁和对乙酰氨基酚处理未导致细胞死亡显著增加。与对照组相比，布比卡因处理导致 Caspase 3 基因表达增加（P = 0.000），对乙酰氨基酚处理也导致 Caspase 3 基因表达增加（P = 0.001）。
我们的数据表明，杜冷丁和托烷司琼对人软骨细胞没有细胞毒性，可能是更常用且更具细胞毒性的布比卡因的更好替代品。对乙酰氨基酚并未导致细胞死亡增加；然而，它确实显示 Caspase 3 基因表达增加，因此应谨慎考虑。
