Functional implications of microvascular heterogeneity for oxygen uptake and utilization

Abstract

In the vascular system, an extensive network structure provides convective and diffusive transport of oxygen to tissue. In the microcirculation, parameters describing network structure, blood flow, and oxygen transport are highly heterogeneous. This heterogeneity can strongly affect oxygen supply and organ function, including reduced oxygen uptake in the lung and decreased oxygen delivery to tissue. The causes of heterogeneity can be classified as extrinsic or intrinsic. Extrinsic heterogeneity refers to variations in oxygen demand in the systemic circulation or oxygen supply in the lungs. Intrinsic heterogeneity refers to structural heterogeneity due to stochastic growth of blood vessels and variability in flow pathways due to geometric constraints, and resulting variations in blood flow and hematocrit. Mechanisms have evolved to compensate for heterogeneity and thereby improve oxygen uptake in the lung and delivery to tissue. These mechanisms, which involve long‐term structural adaptation and short‐term flow regulation, depend on upstream responses conducted along vessel walls, and work to redistribute flow and maintain blood and tissue oxygenation. Mathematically, the variance of a functional quantity such as oxygen delivery that depends on two or more heterogeneous variables can be reduced if one of the underlying variables is controlled by an appropriate compensatory mechanism. Ineffective regulatory mechanisms can result in poor oxygen delivery even in the presence of adequate overall tissue perfusion. Restoration of endothelial function, and specifically conducted responses, should be considered when addressing tissue hypoxemia and organ failure in clinical settings.

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks

“…The heterogeneity of hemodynamic variables in the microcirculation has long been recognized 21,34 and has significant functional implications, for instance with regard to oxygen transport 35 . Such heterogeneity is inevitable as a consequence of known geometrical and developmental constraints on network structure, and compensatory mechanisms (structural adaptation and acute flow regulation) are needed to achieve adequate uniformity of perfusion throughout a tissue despite the underlying heterogeneity 36 .…”

“…The heterogeneity of hemodynamic variables in the microcirculation has long been recognized 21,34 and has significant functional implications, for instance with regard to oxygen transport. 35 Such heterogeneity is inevitable as a consequence of known geometrical are needed to achieve adequate uniformity of perfusion throughout a tissue despite the underlying heterogeneity. 36 Responses to changes in wall shear stress are a key part of these compensatory mechanisms.…”

Devices for assessing microcirculation

“…Microcirculation not only regulates and distributes oxygen (O 2 ), removes carbon dioxide (CO 2 ), and delivers nutrients and hormones but also plays a key role in the immune response, thermoregulation, and coagulation control. Of note, the heterogeneity of its anatomical structure throughout the body is related to the diversity of the functions to be achieved [6 ▪▪ ].…”

“…Microcirculation not only regulates and distributes oxygen (O 2 ), removes carbon dioxide (CO 2 ), and delivers nutrients and hormones but also plays a key role in the immune response, thermoregulation, and coagulation control. Of note, the heterogeneity of its anatomical structure throughout the body is related to the diversity of the functions to be achieved [6 Oxygen transport, in microcirculation, is reached by both convection and diffusion. The former depends on microcirculatory blood flow and O 2 content, which are determined by arteriolar tone and capillary hematocrit, respectively.…”

Heterogeneous ATP patterns in microvascular networks

“…For example, it has been observed experimentally and numerically that the partitioning of RBCs in downstream bifurcations is affected by the flow in upstream bifurcations [38,39]. Due to the complex structure of microvascular networks, a heterogeneous distribution of cells is observed [40,41], affecting chemical signalling as well as oxygen transport [42,43]. These observations constitute a motivation for analysing ATP signalling in a vascular network.…”