The primary role of the circulatory system, and in particular the microcirculation, is to ensure optimal delivery of oxygen to all living cells, under both steady and time-varying conditions. The structural complexity of the microvasculature can have a profound effect on the distribution of oxygen to the surrounding tissue, especially in disease states or when the demand for oxygen is high. Following earlier work in the field, we have developed a flexible, efficient and highly realistic computational model for simulating microvascular blood flow and oxygen delivery. This model has been used to study both steady-state and time-dependent oxygen delivery, which is of primary interest for understanding physiological functioning. Current studies use this model to understand blood flow and oxygen transport during sepsis and the onset of exercise.

The goal of this ongoing project is to increase understanding of physiological processes relevant to normal and pathological phenomena in skeletal muscle and other tissues. In particular, we are interested in the time-course and spatial distribution of hypoxia and anoxia, which can cause localized tissue damage. The interaction between the structural heterogeneity of the microvasculature and the nonlinearity of certain processes, such as blood flow and oxygen consumption, is expected to have important physiological consequences. In sepsis, microvascular blood flow and autoregulation are disturbed, and our model makes it possible to study the consequences for tissue oxygenation. The onset of aerobic exercise, which greatly increases the oxygen consumption rate, is a time-dependent oxygen transport process in which the heterogeneity of microvascular geometry is expected to be important. We are investigating the consequences for tissue oxygen delivery of the interaction between structural and bio-dynamic complexity in the microcirculation in order to increase basic understanding, explain observed phenomena, and examine new approaches for minimizing tissue damage.

Figure: Calculations of steady-state oxygen transport during sepsis. Shown are capillary and tissue oxygen distributions computed using measured hemodynamics and three-dimensional network geometry reconstructed from experimental data. A region of loalized hypoxia can be seen (dark blue).