Laboratoire de physiopathologie mitochondriale, Université Victor Segalen Bordeaux 2, 33076, Bordeaux, France.
Can J Anaesth. 2010 Sep;57(9):836-42. doi: 10.1007/s12630-010-9347-8. Epub 2010 Jul 20.
Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo, the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively.
Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mL x kg(-1)) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections (1 mL x kg(-1)) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponin-skinned muscle fibres using glutamate-malate or succinate as energy substrates.
In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r(2) = 0.74; P < 0.001) and gracilis muscle (r(2) = 0.52; P < 0.001), and there was a significant decrease in the adenosine diphosphate-stimulated oxygen consumption using glutamate or succinate as substrates in both muscles (P < 0.001).
The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip.
布比卡因诱导的肌毒性与线粒体生物能改变有关。布比卡因治疗持续时间对线粒体产能的影响尚不确定。在这里，我们评估了体内不同布比卡因暴露时间（40、56 或 112 小时）对线粒体代谢的改变，这分别对应于 5、7 或 14 次 0.25%布比卡因的重复注射。
大鼠随机分为 7 组：一组无导管对照；三组通过股神经导管每 8 小时注射生理盐水（1 mL·kg(-1))，分别持续 40、56 和 112 小时；三组通过股神经导管每 8 小时注射 0.25%布比卡因（1 mL·kg(-1))，持续 40、56 和 112 小时。研究了位于布比卡因输注-扩散空间内的腰大肌和股薄肌样本。为了估计线粒体呼吸能力，通过测量柠檬酸合酶活性评估线粒体呼吸链装置的蛋白含量。为了测量线粒体呼吸功能，使用谷氨酸-苹果酸或琥珀酸作为能量底物，通过极化法在皂素处理的肌纤维中测量三磷酸腺苷刺激的耗氧量。
在腰大肌和股薄肌中，生理盐水对这两个线粒体参数没有影响。布比卡因导致腰大肌（r(2) = 0.74；P < 0.001)和股薄肌（r(2) = 0.52；P < 0.001)的柠檬酸合酶活性显著降低，并且两种肌肉中使用谷氨酸或琥珀酸作为底物的三磷酸腺苷刺激的耗氧量也显著降低（P < 0.001)。
靠近导管尖端的肌纤维中布比卡因暴露时间与布比卡因诱导的肌毒性严重程度密切相关。
