Bupivacaine-induced muscle injury. The role of extracellular calcium.

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.