Autoregulatory Escape in the Gut: A Systems Analysis

In order to determine whether a metabolic feedback mechanism could account for intestinal autoregulation and autoregulatory escape, we have developed a mathematical model of circulatory control in the gut. The model consists of equations describing hemodynamics, oxygen transport, and local and nervous effects on mesenteric arteriolar and precapillary sphincter tone. We assumed the local system controls intracellular Po2 by (1) regulating arteriolar resistance to change blood flow; and (2) opening or closing precapillary sphincters, thereby determining capillary density (the number of open capillaries) and the diffusion parameters (surface area and diffusion distance). Sympathetic activation increases arteriolar and precapillary sphincter tone. In computer simulations the model responded to step changes in arterial pressure by autoregulating blood flow to control O2 delivery. The degree of autoregulation increased whenever the amount of extractable O2 in the blood decreased. This has been observed experimentally in skeletal muscle but not yet in the intestine. In simulations of autoregulatory escape, sustained sympathetic activation caused a fall in mesenteric blood flow, capillary density, and O2 delivery. Capillary density remained depressed, but blood flow and O2 delivery returned toward control. The end of sympathetic activation was followed by hyperemia and an overshoot in capillary density. These results agree with those obtained experimentally. However, our model predicts that as capillary density is depressed by the sympathetic input, the degree of autoregulatory escape and post-stimulation hyperemia will increase. The degree of autoregulation varied greatly with initial flow conditions, yet the escape index hardly changed. This finding could account for the failure of experimental attempts to correlate the degree of autoregulation with the degree of escape. We conclude that the metabolic feedback hypothesis can adequately explain autoregulation and autoregulatory escape; however, a description complete enough to account for intestinal hemodynamics in some experimental conditions (e.g., venous pressure elevation) must also include certain myogenic properties of the intestinal vasculature.