A model analysis of lactate accumulation during muscle ischemia

Purpose: The mechanistic basis of the relationship between tissue [O-2] and tissue or blood lactate (LA) concentration during tissue hypoxia are not f ully understood. However, blood and tissue lactate accumulation are still u sed as indicators of tissue hypoxia in critically III patients. To investig ate this relationship, we applied a previously developed mathematical model of human bioenergetics to simulate the integrated responses (cellular, tis sue, and whole body) to moderate (10% to 45%) and severe (50% to 80%) reduc tions in muscle blood flow. Materials and Methods: Model simulations of muscle ischemia predicted metab olite concentration changes in muscle, splanchnic bed, and other tissues, a nd were compared with experimental data in humans for model validation. Results: In general, simulations closely predicted the pattern of change in substrates and control metabolites to that observed experimentally. Specif ically, simulations showed that most of the increase in muscle LA productio n during moderate ischemia was due to an increase in pyruvate (PY) and not to the change in redox state induced by a small decrease in O-2 consumption . However, during severe ischemia, changes in [LA]/[PY] ratio in venous blo od corresponded very closely to changes in tissue redox state. Because both blood [LA] and [LA]/[PY] tracked changes in tissue redox state very well, these can be used reliably as indices of tissue hypoxia during severe muscl e ischemia. Conclusions: Based on the simulations, the commonly used threshold value fo r Venous [LA]/[PY] = 14 as evidence of tissue hypoxia seems appropriate dur ing severe ischemia. Copyright (C) 1999 by W.B. Saunders Company.