The human red blood cell (RBC) is known to be susceptible to oxidant d
amage, with both structural and functional properties altered conseque
nt to oxidant attack. Such oxidant-related alterations may lead to cha
nges of RBC theologic behavior (i.e., deformability, aggregability). T
wo different models of oxidant stress were used in this study to gener
ate superoxide anions either internal or external to the RBC. Our resu
lts indicate that generation of superoxide within the RBC by phenazine
methosulfate decreases RBC deformability without effects on cell aggr
egation. Conversely, superoxide generated externally by the xanthine o
xidase-hypoxanthine system primarily affects RBC aggregability: the sh
ear rate necessary to disaggregate RBC was markedly increased while th
e extent of aggregation decreased slightly. Increased disaggregation s
hear rate (i.e., greater aggregate strength) as a result of superoxide
radical damage may adversely affect the dynamics of blood flow in low
-shear portions of the circulation, and may also play a role in the no
-reflow phenomena encountered after ischemia-reperfusion. (C) 1997 Els
evier Science Inc.