Leukocyte deformability and dynamics in the microcirculation in the low flow state

The functional behavior of the leukocyte (white blood cell, WBC) in the microcirculation is often accompanied by undersirable effects on microvascular blood flow which arise from capillary plugging by the less deformable WBCs (compared to red blood cells, RBC's) and their preferential adhesion to the endothelium (EC) of postcapillary venules, which is an essential step in the inflammatory process. Both of these processes may adversely affect microvascular flow as pressure gradients are diminished in the low flow state, although the details of whether plugging or adhesion has a greater effect remains to be determined. To address this question, measurements of the transit time of fluorescently labelled WBCs and RBCs throughout successive microvascular divisions (obtained by indicator dilution techniques under fluorescence microscopy of cremaster muscle) were performed and suggest that the process of cell entrapment within the capillary orifice may proceed to a greater extent without compromising the total throughput of the microvascular network. As capillaries become plugged, alternate pathways for flow are recruited to satisfy tissue metabolic demands. Stimulating WBC-EC adhesion in the normal flow state suggests that microvascular flow is adversely affected by WBC-EC adhesion to a greater extent than capillary plugging by rigid WBCs. Adhesion of as few as 12 WBCs per 100 μm along the length of a 40 μm diameter venule is sufficient to raise flow resistance two-fold. The adverse effects of both capillary plugging and venular obstruction may be exacerbated by reductions in WBC deformability attendant to WBC activation during inflammation. Thus, the relative roles of capillary plugging and WBC-EC adhesion need to be delineated in terms of both flow reductions and the magnitude of the inflammatory process.