Comparison of the effects of endotoxin on limb, respiratory, and cardiac muscles

Abstract

Recent work has shown that endotoxin administration produces reductions in respiratory muscle contractility and an increase in indexes of free radical-mediated lipid peroxidation within these muscles. It is not known, however, whether endotoxin-induced lipid peroxidation occurs only in the respiratory muscles or is a widespread phenomenon affecting all striated muscles. We therefore examined the effects of administration of a range of doses of endotoxin on the isometric force-generating ability and lipid peroxidation of three muscles: the diaphragm (Dia), a leg muscle [i.e., the flexor halluces longus (FHL)], and papillary cardiac muscle (Card). Studies were performed on hamsters divided into groups injected over 2 days with either saline or low, medium, or high doses of endotoxin. The animals were killed on the third study day, force generation by the three muscles was examined in vitro, and the muscles were assayed for 8-isoprostane, an index of lipid peroxidation. We found that endotoxin produced significant reductions in both FHL and Dia force generation, but Card force generation was unaffected. Changes in 8-isoprostane largely paralleled alterations in force, with endotoxin eliciting marked increases in Dia and FHL 8-isoprostane levels but no change in Card 8-isoprostane. These findings suggest that 1) lipid peroxidation and muscle dysfunction in response to endotoxin administration are not limited to the respiratory muscles but also occur in limb skeletal muscle and 2) cardiac muscle appear to be resistant to this particular mechanism of endotoxin-induced dysfunction.