Precapillary servo control of blood pressure and postcapillary adjustment of flow to tissue metabolic status. A new paradigm for local perfusion regulation.

Abstract

There are several shortcomings in current understanding of how the microvasculature maintains tissue homeostasis. Presently unresolved issues include (1) integration of the potentially conflicting needs for capillary perfusion and hydrostatic pressure regulation, (2) an understanding of signal transmission pathways for conveying information about tissue energetic status from undersupplied tissue sites to the arterioles, (3) accounting for the experimentally observed interrelations between precapillary and postcapillary resistances, and (4) an explanation of how precise local adjustment of perfusion to metabolic demands is achieved. A novel conceptualization of how local microvascular control mechanisms are coordinated is proposed, according to which blood flow is adjusted to the metabolic needs of the tissue by the venules. Arteriolar action is merely called on for controlling capillary pressure through myogenic response and shear stress-induced vasodilation. A mathematical model of this theory is introduced and evaluated using well-established experimental data from the literature on regulating mechanisms of microvessel diameters exclusively. The model results demonstrate the suggested mode of microvascular operation to be functional and efficient under conditions present in vivo. Moreover, the predicted vascular responses are large enough to cover the entire range observed in exercising skeletal muscle during adjustment of perfusion to higher performance levels. Precapillary pressure regulation combined with postcapillary adjustment of perfusion to tissue metabolic status is suitable to resolve the above shortcomings in our current understanding of microvascular control. With mathematical modeling based on experimental data, this mode of microvascular operation is shown to be functional and effective in controlling muscle microcirculation.