Chu Constance R, Izzo Nicholas J, Papas Nicole E, Fu Freddie H
Cartilage Restoration Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania 15232, USA.
Arthroscopy. 2006 Jul;22(7):693-9. doi: 10.1016/j.arthro.2006.05.006.
Intra-articular use of 0.5% bupivacaine is common in arthroscopic surgery. This study was conducted to test the hypotheses that (1) 0.5% bupivacaine is toxic to articular chondrocytes, and (2) the intact articular surface protects chondrocytes from the effects of short-term exposure to 0.5% bupivacaine.
Freshly isolated bovine articular chondrocytes were prepared into alginate bead cultures and were treated with 0.5% bupivacaine solution or 0.9% saline for 15, 30 or 60 minutes, washed, and returned to growth media. Chondrocytes were recovered from alginate 1 hour, 1 day, and 1 week after bupivacaine exposure; they were fluorescently labeled to identify apoptotic and dead cells and were analyzed by flow cytometry. Twelve osteochondral cores were harvested from bovine knees. The superficial 1 mm of cartilage was removed from 6 cores (top-off). Intact and top-off cores were submerged in 0.9% saline or 0.5% bupivacaine solution for 30 minutes and then maintained in chondrocyte growth media for 24 hours. Live-cell/dead-cell fluorescent imaging was assessed using confocal microscopy.
Greater than 99% chondrocyte death/apoptosis was observed in all bupivacaine-exposed alginate bead cultures compared with 20% cell death in saline-treated controls (P < .05). Osteochondral cores with intact surfaces treated with 0.5% bupivacaine showed 42% dead chondrocytes. When the articular surface was removed, 0.5% bupivacaine resulted in increased cell death, with 75% dead chondrocytes (P < .05).
Results show that 0.5% bupivacaine solution is cytotoxic to bovine articular chondrocytes and articular cartilage in vitro after only 15 to 30 minutes' exposure. The intact bovine articular surface has some chondroprotective effects.
Because healthy chondrocytes are important for maintenance of the cartilage matrix, chondrocyte loss may contribute to cartilage degeneration. This study shows a cytotoxic effect of 0.5% bupivacaine solution on bovine articular chondrocytes in vitro. Although these results cannot be directly extrapolated to the clinical setting, the data suggest that caution should be exercised in the intra-articular use of 0.5% bupivacaine.
0.5%布比卡因在关节镜手术中常用于关节腔内。本研究旨在验证以下假设：（1）0.5%布比卡因对关节软骨细胞有毒性；（2）完整的关节表面可保护软骨细胞免受短期暴露于0.5%布比卡因的影响。
将新鲜分离的牛关节软骨细胞制备成藻酸盐珠培养物，用0.5%布比卡因溶液或0.9%生理盐水处理15、30或60分钟，冲洗后放回生长培养基中。在布比卡因暴露后1小时、1天和1周从藻酸盐中回收软骨细胞；对其进行荧光标记以识别凋亡和死亡细胞，并通过流式细胞术进行分析。从牛膝关节采集12个骨软骨芯。从6个芯中去除表面1mm的软骨（顶部切除）。将完整和顶部切除的芯浸入0.9%生理盐水或0.5%布比卡因溶液中30分钟，然后在软骨细胞生长培养基中培养24小时。使用共聚焦显微镜评估活细胞/死细胞荧光成像。
与生理盐水处理的对照组中20%的细胞死亡相比，在所有暴露于布比卡因的藻酸盐珠培养物中观察到超过99%的软骨细胞死亡/凋亡（P <.05）。用0.5%布比卡因处理的表面完整的骨软骨芯显示42%的软骨细胞死亡。当去除关节表面时，0.5%布比卡因导致细胞死亡增加，75%的软骨细胞死亡（P <.05）。
结果表明，仅暴露15至30分钟后，0.5%布比卡因溶液在体外对牛关节软骨细胞和关节软骨具有细胞毒性。完整的牛关节表面具有一定的软骨保护作用。
由于健康的软骨细胞对维持软骨基质很重要，软骨细胞的丢失可能导致软骨退变。本研究显示0.5%布比卡因溶液在体外对牛关节软骨细胞具有细胞毒性。尽管这些结果不能直接外推至临床情况，但数据表明在关节腔内使用0.5%布比卡因时应谨慎。
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