Early ultrastructural changes in skeletal muscle exposed to the local anaesthetic bupivacaine (Marcaine)

Abstract

The local anaesthetic drug bupivacaine is known to produce a degeneration in mammalian muscle fibres which is followed by regeneration. In an attempt to define the site of action of this drug and the cell type responsible for the subsequent fibre regeneration, first lumbircal muscles of rats were exposed in vitro to concentrations of 10(-2), 5 X 10(-3), and 10(-3)M bupivacaine for periods ranging from 5 min to 3 h. An electron microscopic study of muscles exposed to 10(-2) and 5 X 10(-3)M bupivacaine revealed an initial supercontraction followed by evidence of severe and probably irreversible injury to plasma membrane, sarcoplasmic reticulum and mitochondria. Myonuclei showed signs of injury early, but satellite cells were found relatively resistant. The basal lamina remained intact throughout and myelinated axons did not suffer damage. However, both endothelial cells of capillaries and fibrocytes showed degenerative changes. Muscles exposed to 10(-3)M bupivacaine showed little change after incubation for 3 h. It is concluded that increased intracellular levels of Ca++ ions may play a part in the pathogenesis of muscle injury induced by bupivacaine and that their source may be the sarcoplasmic reticulum. The role of the satellite cell in the regeneration that follows this injury was not clearly established.