Intrinsic microvascular control of tissue oxygen delivery

A systems analysis of intrinsic regulation of oxygen delivery in skeletal muscle is presented. The model includes the following: microvasculature divided into resistance (arteriolar), exchange (capillary) and capacitance (venous) sections; transcapillary O 2 flux is a function of capillary P O 2 , cell P O 2 , and effective capillary density; resting intracellular P O 2 (5 mm Hg) operating at the critical oxygen tension, i.e., cells on brink of hypoxia; nonlinear relationship between mitochondrial O 2 utilization and cell P O 2 ; nonlinear hemoglobin dissociation curve; and integral control of cell P O 2 via metabolic modulation of arteriolar and precapillary sphincter tone. Basically, flow regulation by the arterioles minimizes changes in capillary P O 2 when the system is stressed, whereas the precapillary sphincters regulate the number of open capillaries and thereby determine oxygen diffusion parameters (diffusion distance and surface area). In the absence of arteriolar and sphincter feedback, an important consequence of the low cell P O 2 is that cellular hypoxia occurs whenever the O 2 availability: demand ratio is reduced. The greater sensitivity of the sphincters to metabolic control relative to that of the arterioles is the basis for the following simulation results: (1) following slight to moderate reductions in the availability: demand ratio, tissue oxygen delivery is maintained primarily by increased extraction of O 2 from blood; (2) with more severe reduction of this ratio, arteriolar flow control becomes more important in maintaining adequate tissue oxygenation; (3) in response to a step decrease in arterial pressure, the degree of blood flow autoregulation increases as the initial venous oxygen concentration decreases. These results suggest that as metabolic stresses become greater the major locus of intrinsic microvascular control moves from the normally more powerful sphincters to the upstream arterioles.