Distinct roles of red-blood-cell-derived and wall-derived mechanisms in metabolic regulation of blood flow.

OBJECTIVE A theoretical model is used to analyze combinations of RBC-derived and wall-derived (RBC-independent) mechanisms for metabolic blood flow regulation, with regard to their oxygen transport properties. METHODS Heterogeneous microvascular network structures are derived from observations in rat mesentery and hamster cremaster. The effectiveness of metabolic blood flow regulation using combinations of RBC-dependent and RBC-independent mechanisms is simulated in these networks under conditions of reduced oxygen delivery and increased oxygen demand. RESULTS Metabolic regulation by a wall-derived mechanism results in higher predicted total blood flow rate and number of flowing vessels, and lower tissue hypoxic fraction, than regulation by combinations of RBC-derived and wall-derived signals. However, a combination of RBC-derived and wall-derived signals results in a higher predicted median tissue PO2 than either mechanism acting alone. CONCLUSIONS Model results suggest complementary roles for RBC-derived and wall-derived mechanisms of metabolic flow regulation, with the wall-derived mechanism responsible for avoiding hypoxia, and the RBC-derived mechanism responsible for maintaining PO2 levels high enough for optimal tissue function.