Steer J H, Mastaglia F L, Papadimitriou J M, Van Bruggen I
J Neurol Sci. 1986 Apr;73(2):205-17. doi: 10.1016/0022-510x(86)90131-0.
To investigate the role of extracellular calcium in bupivacaine-induced muscle injury, the effects of the drug on creatine kinase (CK) release and muscle ultrastructure were studied in the isolated rat soleus in the presence and absence of calcium and of the Ca-channel blockers verapamil and nifedipine. Control muscles maintained a constant CK release rate and normal morphology for at least 3 hours. CK release rates increased markedly after exposure to 1.5 mM and 5 mM bupivacaine and electron microscopy showed evidence of damage to mitochondria, sarcoplasmic reticulum and the plasmalemma of muscle fibres with disruption of the Z-lines, I-bands and M-lines of myofibrils. When calcium was omitted from the incubation medium, there was a 3-fold reduction in CK release rates; the morphological changes were less severe initially but by 120 min were comparable to those in muscles incubated with bupivacaine and calcium. Neither 10(-6) M verapamil nor 10(-6) M nifedipine reduced CK release or muscle fibre damage. Verapamil (10(-5) M) reduced CK release but not the severity of muscle damage. The findings indicate that extracellular calcium plays a part in mediating the muscle damage caused by bupivacaine but that other factors must also be involved, and that Ca-channel blockers do not prevent muscle damage.
为研究细胞外钙在布比卡因诱导的肌肉损伤中的作用，在有无钙以及存在钙通道阻滞剂维拉帕米和硝苯地平的情况下，研究了该药物对离体大鼠比目鱼肌肌酸激酶（CK）释放和肌肉超微结构的影响。对照肌肉在至少3小时内维持恒定的CK释放速率和正常形态。暴露于1.5 mM和5 mM布比卡因后，CK释放速率显著增加，电子显微镜显示线粒体、肌浆网和肌纤维质膜受损，肌原纤维的Z线、I带和M线破坏。当孵育培养基中不含钙时，CK释放速率降低了3倍；形态学变化最初较轻，但到120分钟时与用布比卡因和钙孵育的肌肉中的变化相当。10^(-6) M维拉帕米和10^(-6) M硝苯地平均未降低CK释放或肌肉纤维损伤。维拉帕米（10^(-5) M）降低了CK释放，但未减轻肌肉损伤的严重程度。研究结果表明，细胞外钙在介导布比卡因引起的肌肉损伤中起作用，但也必定涉及其他因素，并且钙通道阻滞剂不能预防肌肉损伤。
