Theoretical Models of Blood Flow Regulation

Abstract

In normal tissues, blood supply is closely matched to tissue demand for wide ranges of oxygen demand and arterial pressure. This suggests that multiple mechanisms regulate blood flow. Theoretical models can be used to analyze these interacting mechanisms. One proposed mechanism for metabolic flow regulation involves the saturation-dependent release of ATP by red blood cells, which triggers an upstream conducted response signal and arteriolar vasodilation. To analyze this mechanism, oxygen and ATP levels are calculated along a flow pathway of seven representative segments, including two vasoactive arteriolar segments. The conducted response signal is dependent on ATP concentration. Arteriolar tone depends on the conducted response signal, local wall shear stress and wall tension. Arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model can account for increases in perfusion consistent with experimental findings at low and moderate oxygen consumption rates despite the opposing effects of the myogenic and shear-dependent responses. Autoregulation, the maintenance of nearly constant blood flow as arterial pressure varies, is assessed in the presence or absence of the myogenic, shear-dependent and/or metabolic responses. The model results indicate that the combined effects of myogenic and metabolic regulation overcome the vasodilatory effect of the shear-dependent response to generate autoregulatory behavior. Capillary recruitment has been shown to increase the capacity for oxygen delivery during exercise. In the model, capillary density is assumed to depend on small arteriole diameter. The model predicts a significant increase in the range over which perfusion can be regulated when recruitment is included. Oscillations in diameter and tone are predicted under certain conditions, suggesting a novel mechanism for vasomotion. The conditions that give rise to oscillations are analyzed. It is shown that the appearance of oscillations depends in a complex way on a number of system parameters. In summary, the theoretical model provides a quantitative assessment of the myogenic, shear-dependent and metabolic responses that affect blood flow regulation and identifies a role for capillary recruitment and vasomotion in the control of blood flow.