Effect of Decreased Oxygen Supply on Skeletal Muscle Oxygenation and Oxygen Consumption during Sepsis: Role of Heterogeneous Capillary Spacing and Blood Flow

One of the main aspects of the initial phase of the septic inflammatory response to a bacterial infection is abnormal microvascular perfusion, including decreased functional capillary density (FCD) and increased blood flow heterogeneity. On the other hand, one of the most important phenomena observed in the later stages of sepsis is an increased dependence of tissue O 2 utilization on the convective O 2 supply. This " pathological supply dependency " is associated with organ failure and poor clinical outcomes. Here, a detailed theoretical model of capillary-tissue O 2 transport during sepsis is used to examine the origins of abnormal supply dependency. Using three-dimensional arrays of capillaries with heterogeneous spacing and blood flow, steady-state O 2 transport is simulated numerically during reductions in the O 2 supply. Increased supply dependency is shown to occur in sepsis for both hypoxic hypoxia (decreased hemoglobin O 2 saturation) and stagnant hypoxia (decreased blood flow). For stagnant hypoxia, it is found that a reduction in FCD with decreasing blood flow is necessary to obtain the observed increase in supply dependency. Our results imply that supply dependency observed under normal conditions does not have its origin at the level of individual capillaries. However, in sepsis diffusion limitation and shunting of O 2 by individual capillaries occur to a degree dependent on the heterogeneity of septic injury and the arrangement of capillary networks. Thus, heterogeneous stoppage of individual capillaries is a likely factor in pathological supply dependency.