EFFECTS OF LEUKOCYTE-CAPILLARY PLUGGING ON THE RESISTANCE TO FLOW IN THE MICROVASCULATURE OF CREMASTER MUSCLE FOR NORMAL AND ACTIVATED LEUKOCYTES

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). IIA-V was calculated from simulta neous 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 tim es systemic resulted in insignificant transient increases in R(A-V) of 5 to 10%. The effect of WBC activation was studied by their incubatio n in N-formyl-methionyl-leucyl-phenylalanine (FMLP) to activate (and s tiffen) the polymorphonulear WBCs (PMNs) or phorbal myristate acetate (PMA) to activate all WBCs in the bolus. Compared with normal WBCs, in fusions of mixtures of RBCs and activated WBCs had no significant effe ct on the transient increase in resistance as the bolus traversed the capillary network. However, mixtures with either normal or FMLP-treate d WBCs increased the steady state RA-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 x 10(6) normal or FMLP-activated WBCs resulted in a 25% increase in R(A-V) above baselin e. With PMA activation, cumulative infusions of only 5 x 10(6) WBCs in the RBC suspension also resulted in a 25% increase in R(A-V), which w as three times the increase obtained for an equal number of FMLP activ ated WBCs. Following the cumulative infusion of 12 x 10(6) PMA-activat ed WBCs, R(A-V) increased inordinately to approximately 250% of baseli ne. These substantially greater increases in capillary plugging and RA -V With PMA activation were in accord with the threefold greater numbe r 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 microvascul ature compared to normal WBCs, and the extent of this effect is strong ly dependent on the number of activated WBCs in the circulation. (C) 1 996 Academic Press, Inc.