Causes for spatial heterogeneity of perfusion and function

Abstract

In many tissues, including the heart, perfusion and metabolic activity are heterogeneous and spatially correlated. To investigate the underlying mechanisms and cause/effect relations, a mathematical simulation model based on experimental data for microvascular networks was used. Results show that unavoidable geometric heterogeneities of vascular networks cause heterogeneity of blood flow and oxygen levels which cannot be eliminated by increasing metabolic sensitivity of diameter adaptation. Additional adaptation of oxygen demand to local oxygen availability allows increased oxygen extraction and functional capacity. It also establishes a correlation between local oxygen demand and flow rate, as observed experimentally. These findings suggest that stochastic processes of angiogenesis and not pre‐existing heterogeneities of local metabolic demand underlie the observed spatial heterogeneity of perfusion and function.