Oxygen Mediated Blood Flow Regulation in Microvascular Networks

The human microcirculation is a complex branching system composed of over 35,000 km of blood vessels ranging in diameter from 4 – 300 µm. Blood flow distribution in microvascular networks is dynamically controlled via intrinsic and extrinsic regulatory mechanisms that match the delivery of blood to meet the nutritive demands of all cells in the body. In skeletal muscle, aerobic metabolism requires adequate oxygen to be delivered throughout the tissue and appropriately distributed between heterogeneous regions of variably oxidative fibres. Numerous mechanisms have been identified for the modulation of blood flow at the arteriolar level but little consensus exists regarding how oxygen sensing contributes to vascular control and the resulting targeted distribution of flow to capillary networks. The integrated nature of vascular control presents numerous challenges for studying blood vessels and blood flow both in vitro and in vivo. Current techniques leverage a variety of imaging modalities which allow for observation of intact vasculature in animal models to be combined with quantitative in vivo measurements. Our recent work has established the complex interplay between blood flow, vascular structure, flow distribution, oxygen saturation, and tissue metabolism by combining in vivo measurements with mathematical models. We will discuss how these techniques are used to study oxygen delivery and how novel experimental approaches are being developed to interrogate mechanisms of oxygen mediated blood flow regulation.