Sola M, Dahners L, Weinhold P, Svetkey van der Horst A, Kallianos S, Flood D
University of North Carolina, Orthopaedic Research Labs, 134B Glaxo Building. CB# 7546, 101A Mason Farm Rd. Chapel Hill, North Carolina 27599, USA.
University of North Carolina, CB #7055, Bioinformatics Building, Chapel Hill, North Carolina 27599-7055, USA.
Bone Joint J. 2015 Jul;97-B(7):933-8. doi: 10.1302/0301-620X.97B7.35398.
This in vivo controlled laboratory study was performed to evaluate various intra-articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH-balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague-Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live-dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone. Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity.
本体内对照实验室研究旨在评估各种关节内临床注射方案,这些方案的毒性可能低于一些体外研究的结果。我们假设,低浓度、无防腐剂、pH值平衡的药物比高浓度、含防腐剂且pH值不平衡的药物毒性更低,并且单独注射药物的毒性低于联合注射。对12至13周龄的Sprague-Dawley大鼠的左膝进行一次注射,注射八种不同的单一药物,包括低浓度和高浓度的罗哌卡因和曲安奈德,单独注射和联合注射,以及阴性和阳性对照。在1周或5个月时处死大鼠,并进行活死染色以量化软骨细胞的死亡情况。与对照膝关节相比,除pH值平衡的0.2%罗哌卡因与无防腐剂的1mg/ml曲安奈德联合注射外,所有注射在1周和5个月后均导致软骨细胞活力出现统计学显著下降(p<0.001)。1周后,0.2%和0.5%罗哌卡因之间的活力无显著差异;然而,4mg/ml曲安奈德导致的活力低于1mg/ml曲安奈德。尽管许多常用于关节注射的药物具有软骨毒性,但在本体内研究中,将无防腐剂的10mg/ml曲安奈德以1:9的比例稀释于0.2%pH值平衡的罗哌卡因中,毒性较低。