Additive effect of red blood cell rigidity and adherence to endothelial cells in inducing vascular resistance

Abstract

Kaul DK, Koshkaryev A, Artmann G, Barshtein G, Yedgar S. Additive effect of red blood cell rigidity and adherence to endothelial cells in inducing vascular resistance. Am J Physiol Heart Circ Physiol 295: H1788 -H1793, 2008. First published August 29, 2008 doi:10.1152/ajpheart.253.2008.-To explore the contribution of red blood cell (RBC) deformability and interaction with endothelial cells (ECs) to circulatory disorders, these RBC properties were modified by treatment with hydrogen peroxide (H2O2), and their effects on vascular resistance were monitored following their infusion into rat mesocecum vasculature. Treatment with 0.5 mM H2O2 increased RBC/EC adherence without significant alteration of RBC deformability. At 5.0 mM H2O2, RBC deformability was considerably reduced, inducing a threefold increase in the number of undeformable cells, whereas RBC/EC adherence was not further affected by the increased H2O2 concentration. This enabled the selective manipulation of RBC adherence and deformability and the testing of their differential effect on vascular resistance. Perfusion of RBCs with enhanced adherence and unchanged deformability (treatment with 0.5 mM H2O2) increased vascular resistance by about 35% compared with untreated control RBCs. Perfusion of 5.0 mM H 2O2-treated RBCs, with reduced deformability (without additional increase of adherence), further increased vascular resistance by about 60% compared with untreated control RBCs. These results demonstrate the specific effects of elevated adherence and reduced deformability of oxidized RBCs on vascular resistance. These effects can be additive, depending on the oxidation conditions. The oxidation-induced changes applied in this study are moderate compared with those observed in RBCs in pathological states. Yet, they caused a considerable increase in vascular resistance, thus demonstrating the potency of RBC/EC adherence and RBC deformability in determining resistance to blood flow in vivo. erythrocyte rheology; aggregability; adhesion; circulatory disorders RED BLOOD CELLS (RBCs) have special flow-affecting properties that are major determinants of blood flow: deformability, RBC-RBC aggregability, and RBC/endothelial cell (EC) adherence.

Storage-Induced Damage to Red Blood Cell Mechanical Properties Can Be Only Partially Reversed by Rejuvenation

“…3A) and by the percentage of UDC (fig. 3B) in the RBC population [5,18,31,32]. Figure 3A, depicting a representative ER curve, shows that cold storage induced an overall reduction in RBC deformability as shown by the shift of the St-RBC curve to lower ER values (elevation of the presence of low-deformable cells in the population) compared to F-RBC, and this was improved by rejuvenation.…”

“…Accordingly, RBC with ER E 1.1 are defined as ‘undeformable' cells (UDC), namely cells that do not deform under high shear stress (3.0 Pa). As shown and discussed in our previous studies, when considering the potential of reduced RBC deformability to induce microvascular occlusion, the portion of UDC is more clinically relevant than the shift in average values [30,31,32]. …”

“…Although this method does not measure methemoglobin and oxidized forms of hemoglobin (which comprise about 1-3% of the total hemoglobin), it is commonly used when measuring experimentally induced RBC lysis [21,30,31]. The hemolysis level (% hemolysis) was calculated according to the following formula:…”

Deformability of Red Blood Cells and Correlation with ATP Content during Storage as Leukocyte-Depleted Whole Blood

“…Possible mechanisms explaining this association are the 2,3-diphosphoglycerate (2,3-DPG) deficiency of stored red cells, which results in a reduced capacity of the red cells to release oxygen to the tissues, and an increased rigidity of the red cells. This increased rigidity results in elevated adherence to endothelial cells [10], precluding them from readily passing small capillaries [11], and leading to increased vascular resistance [12]. Several randomized clinical trials are under way to clarify this issue [7].…”

Effect of Free Radical Generating System- Adenosine Triphosphate/Ferrous Sulphate/Hydrogen Peroxide on Human Erythrocytes

“…Experimentally induced erythrocyte lysis was determined by measuring hemoglobin optical density (OD) at 540nm [19][20]. The hemolysis level (% hemolysis) was calculated according to the following formula: % Hemolysis =100*(ODT-ODC)/ (ODTotal-ODC) where the ODC denotes OD of supernatant obtained for control (no stress) erythrocytes, ODT denotes OD of supernatant of erythrocytes subjected to oxidative stress and ODTotal correspond to the hemolysis obtained by conventional incubation (10 min) of erythrocytes in water [21].…”