MICROVASCULAR RESEARCH 51, 187–201 (1996) ARTICLE NO. 0020 Effects of Leukocyte-Capillary Plugging on the Resistance to Flow in the Microvasculature of Cremaster Muscle for Normal and Activated Leukocytes M. J. EPPIHIMER AND H. H. LIPOWSKY Bioengineering Program, Pennsylvania State University, University Park, Pennsylvania 16802 Received July 10, 1995 The effects of leukocyte (WBC) sequestration in the capillary network on resistance to flow (R A-V ) were obtained during bolus infusions of WBCs in cremaster muscle (hamster). R A-V was calculated from simultaneous measurements of arteriole to venule pressure drop and arteriolar red cell velocity. Bolus infusions of red cells (RBCs) alone resulted in a 5% decrease in R A-V , due to the clearance of circulating WBCs from the network. Infusions of RBCs with leukocrits of one to nine times systemic resulted in insignificant transient increases in R A-V of 5 to 10%. The effect of WBC activation was studied by their incubation in N-formyl-methionyl-leucyl- phenylalanine (FMLP) to activate (and stiffen) the polymorphonulear WBCs (PMNs) or phorbal myristate acetate (PMA) to activate all WBCs in the bolus. Compared with normal WBCs, infusions of mixtures of RBCs and activated WBCs had no significant effect on the transient increase in resistance as the bolus traversed the capillary network. However, mixtures with either normal or FMLP-treated WBCs increased the steady state R A-V in proportion to the cumulative number of WBCs infused, due to residual capillary plugging following washout of the bolus. The cumulative infusion of 20 1 10 6 normal or FMLP-activated WBCs resulted in a 25% increase in R A-V above baseline. With PMA activation, cumulative infusions of only 5 1 10 6 WBCs in the RBC suspension also resulted in a 25% increase in R A-V , which was three times the increase obtained for an equal number of FMLP-activated WBCs. Following the cumulative infusion of 12 1 10 6 PMA-activated WBCs, R A-V increased inordinately to approximately 250% of baseline. These substantially greater increases in capillary plugging and R A-V with PMA activation were in accord with the threefold greater number of stiffened lymphocytes (which do not respond to FMLP) relative to PMNs in the boli. Thus, capillary plugging by activated WBCs may have a far greater detrimental effect on blood flow through the microvasculature compared to normal WBCs, and the extent of this effect is strongly dependent on the number of activated WBCs in the circulation.  1996 Academic Press, Inc. INTRODUCTION Leukocyte (white blood cell, WBC) plugging of capillaries has been suggested as the principal cause of increased resistance to blood flow in ischemic (Engler et al., 1983) and low flow (Bagge et al., 1980) disorders, as well as in response to reductions in WBC deformability attendant to their activation with inflammation (Barraso-Aranda and Schmid-Scho ¨nbein, 1989). Many studies have assessed pressure–flow relation- ships of isolated organs during the perfusion of WBC suspensions (Braide et al., 1984, 1986, 1989; Sutton and Schmid-Schonbein, 1992) and have demonstrated that WBCs may contribute as much as 20% of the total resistance to flow under normal perfusion 187 0026-2862/96 $18.00 Copyright  1996 by Academic Press, Inc. All rights of reproduction in any form reserved.