Nouette-Gaulain Karine, Sirvent Pascal, Canal-Raffin Mireille, Morau Didier, Malgat Monique, Molimard Mathieu, Mercier Jacques, Lacampagne Alain, Sztark François, Capdevila Xavier
Laboratoire de Physiologie Mitochondriale, Unité INSERM U688, Université Victor Ségalen Bordeaux 2, Bordeaux, France.
Anesthesiology. 2007 May;106(5):1026-34. doi: 10.1097/01.anes.0000265164.29630.b4.
Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca(2+) release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.
Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.
Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 microg/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.
Bupivacaine, levobupivacaine, and ropivacaine injected via femoral nerve block catheters induce a deleterious effect in mitochondrial energy, whereas only levobupivacaine disturbs calcium homeostasis.
长效局部麻醉药会导致肌肉损伤。此外，长效局部麻醉药在分离的线粒体中可作为氧化磷酸化的解偶联剂，并增强肌浆网Ca(2+)释放。本研究的目的是评估局部麻醉药经神经周围注射对体内线粒体能量代谢和细胞内钙稳态的影响。
将股神经阻滞导管插入成年雄性Wistar大鼠体内。大鼠被随机分组，并以8小时的间隔接受七次注射（1毫升/千克）的布比卡因、左旋布比卡因、罗哌卡因或等渗盐水。在最后一次注射后8小时处死大鼠。从股神经旁迅速解剖出腰大肌。测定肌肉中局部麻醉药的浓度。在皂素处理的肌纤维中测量氧化能力。测量氧气消耗率，并测定线粒体三磷酸腺苷合成率。评估线粒体呼吸链复合物的酶活性。分析局部钙释放事件（钙火花）以及皂素处理的肌纤维中肌浆网钙含量。
最后一次注射后8小时，腰大肌中局部麻醉药浓度低于0.3微克/克组织。接受局部麻醉药治疗的大鼠肌肉中的三磷酸腺苷合成和三磷酸腺苷与氧气的比率显著降低。观察到呼吸链所有酶活性总体下降（约50%）。左旋布比卡因增加了钙火花的幅度和频率，而肌浆网钙含量较低。
通过股神经阻滞导管注射布比卡因、左旋布比卡因和罗哌卡因会对线粒体能量产生有害影响，而只有左旋布比卡因会扰乱钙稳态。
