ULTRASTRUCTURAL-CHANGES IN SKELETAL-MUSCLE MITOCHONDRIA IN GRAM-NEGATIVE SEPSIS

Energy metabolism during sepsis is incompletely understood, but altera tions in mitochondrial structure and function appear important. We mea sured time-dependent changes in mitochondrial structure during sepsis using serial skeletal muscle biopsies in anesthetized baboons injected with 10(10) CFU/kg of live Escherchia coli (LD(100)), Skeletal muscle biopsies were taken before bacterial challenge (0 h controls) and at 12 h, 24 h, and death, By qualitative electron microscopy, the organel les became enlarged with distorted cristae and developed electron luce nt areas within the matrix. With advanced injury the inner membrane be came fragmented. Quantitative morphometric analysis showed a 50% incre ase in mean cristal membrane surface density by 24 h (p < .05) accompa nied by a 100% increase in intermembrane space (p < .01). Matrix volum e density decreased progressively (p < .01), These changes in mitochon drial ultrastructure occur within 12 h after the onset of the bacteria l insult. This damage, including destruction or reorganization of both membrane and matrix proteins, is severe enough to compromise oxidativ e metabolism in muscle in Gram-negative sepsis.