Capillary recruitment in response to tissue hypoxia and its dependence on red blood cell deformability

The effect of reduced red blood cell (RBC) deformability on microvessel recruitment attendant to a reduction in tissue PO₂ was studied in rat cremaster muscle using indicator-dilution techniques. Transit times (TT) of fluorescently labeled RBCs (TT(RBC)) and plasma (TT(Pl)) between functionally paired arterioles and venules were obtained from their dispersion throughout the microvascular network. Changes in PO₂ were effected by superfusing the tissue with Ringer solution deoxygenated to different levels. Arteriolar blood flow (Q) was measured with the two-slit technique, and the vascular volume (V) occupied by. RBCs and plasma was computed from the product of Q x TT during bolus infusions of rat and less deformable human RBCs to obtain V(RBC) and fluorescently labeled albumin to obtain V(Pl). Measurements of TT(RBC) and TT(Pl) permitted computation of an average flow-weighted tissue (microvascular) hematocrit (H(M)) relative to systemic values (H(S)). During infusions of autologous rat RBCs, Q and total V increased threefold in response to hypoxia, whereas normalized RBC TT (TT(RBC)/TT(Pl)) and normalized tissue hematocrit (H(M)/H(S)) did not show a significant trend, indicating an increase in the number of pathways through which the RBCs can traverse the network because of spatial recruitment of capillaries. In contrast, during infusions of human RBCs, TT(RBC)/TT(Pl) and H(M)/H(S) decreased significantly in response to hypoxia. Although Q exhibited an increase similar to that during rat RBC infusions, V(RBC) exhibited a smaller increase compared with V(Pl), suggesting that reduced RBC deformability leads to a redistribution of RBCs through larger-diameter pathways within the network and exclusion of these RBCs from pathways normally recruited during hypoxia. Hence, reduced RBC deformability may adversely affect capillary recruitment and physiological mechanisms that ensure adequate delivery of oxygen to tissue.