Leukocyte sequestration in the microvasculature in normal and low flow states

Techniques of indicator dilution were applied to determine the relative transit times (TTs) of fluorescently labeled leukocytes (TT(WBC)), red blood cells (TT(RBC)), and plasma (TT(pl)) between functionally paired arterioles and venules in hamster cremaster muscle in normal and low flow states. In the normal flow state, paired measurements of TT(WBC)/TT(pl) in arteriovenous (A- V) pairs bounding the true capillaries averaged 0.75 = 0.08 (SE) s and were not significantly different from an average TT(RBC)/TT(pl) of 0.78 ± 0.06 (SE) s as WBCs appeared to traverse the capillary segment through more centralized preferential pathways. In larger-diameter A-V pairs, significantly larger (10%) values of TT(WBC)/TT(pl) were found compared with TT(RBC)/TT(pl) due to margination of WBCs in postcapillary venules. To assess the relative effects of WBC-capillary plugging and WBC adhesion in venules on flow resistance. TT(WBC) was measured in normal and low flow states, with the latter induced by systemic administration of sodium nitroprusside, which resulted in an increase in TT(pl) from a norm of 1.08 ± 0.16 to 2.62 ± 0.44 (SE) s (P < 0.05). With onset of the low flow state, TT(WBC)/TT(pl), the number of plugged capillaries, and the duration of capillary plugs did not change significantly from the norm. In contrast, the rate at which WBC- endothelium (-EC) adhesion increased with successive bolus injections increased approximately eight-fold during hypoperfusion. Estimates of the percentage increase in segmental resistance at the capillary level (due to plugging) and in postcapillary venules (due to EC adhesion) revealed that venous resistance may increase at a threefold greater rate due to WBC sequestration with each successive bolus infusion. Inasmuch as hemodynamic resistance in capillary and venular segments is of the same order of magnitude in the normal flow state, it appears that WBC adhesion in venules may have a far greater deleterious effect on microvascular blood flow in the low flow state.