Ultrastructural changes in skeletal muscle mitochondria in gram-negative sepsis

Energy metabolism during sepsis is incompletely understood, but alterations in mitochondrial structure and function appear important. We measured time-dependent changes in mitochondrial structure during sepsis using serial skeletal muscle biopsies in anesthetized baboons injected with 10(10) CFU/kg of live Escherichia 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 organelles became enlarged with distorted cristae and developed electron lucent areas within the matrix. With advanced injury the inner membrane became fragmented. Quantitative morphometric analysis showed a 50% increase in mean cristal membrane surface density by 24 h (p < .05) accompanied by a 100% increase in intermembrane space (p < .01). Matrix volume density decreased progressively (p < .01). These changes in mitochondrial ultrastructure occur within 12 h after the onset of the bacterial insult. This damage, including destruction or reorganization of both membrane and matrix proteins, is severe enough to compromise oxidative metabolism in muscle in Gram-negative sepsis.