The effect of sildenafil on the elasticity of erythrocytes in homozygous sickle cell disease.

Purpose: One of the features of homozygous sickle cell disease (HbSS) is the impaired elasticity of the erythrocyte membrane that could impede microcirculatory blood flow and cause hypoxia and tissue damage. We investigated the effect of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor that inhibits the breakdown of cyclic guanosine monophosphate (cGMP) resulting in vasodilatation, on the elasticity of HbSS erythrocyte. Materials and Methods: Blood samples from ten HbSS patients in steady state was exposed to different doses (5, 10, 20, and 40 μg/mL) of sildenafil and the elasticity of the erythrocytes measured at native hematocrit with the BioProfiler. An equal number of subjects with normal hemoglobin (HbAA) served as the control group. Results: There was a marginal increase in elasticity with 5 μg/mL of the drug and this became significant (P < 0.05) with the 10 μg/mL dose. Thereafter, gradual nonsignificant decreases were observed with the 20 and 40 μg/mL doses. A similar trend was observed for the control group. The elasticity values for the HbSS subjects at native hematocrit were significantly (P < 0.05) less when compared with the corresponding concentrations for the HbAA controls. This was reversed at a corrected hematocrit of 45%. Conclusion: The result of this study shows that sildenafil caused an initial increase in erythrocyte membrane elasticity in both HbSS and HbAA subjects, and this later decreased with increasing concentration of the drug possibly due to the dual effect of cyclic adenosine monophosphate (cAMP).

Assessment of Hemorheological Deformability of Human Red Cells Exposed to tert-Butyl Hydroperoxide, Verapamil and Ascorbate by Ektacytometer / 대한진단검사의학회지

BACKGROUND: Normal erythrocyte is deformable and this facilitates blood flow in the capillaries. Oxidative stress reduces the deformability of erythrocytes, and influences on blood flow in microcirculation. The objective of this study was to investigate the deformability of erythrocytes exposed to oxidative stress, the protective effects of verapamil and ascorbic acid against oxidative damages in erythrocytes, and the value of the microfluidic ektacytometer, RheoScan-D (RheoMeditech, Korea) in clinical application. METHODS: Effects of oxidative stress on erythrocytes were investigated using tert-butyl hydroperoxide (tBHP). Before exposure to tBHP, the erythrocytes were pretreated with verapamil and ascorbic acid to examine their protective effect against oxidative damages. The deformability of erythrocytes was measured by the microfluidic ektacytometer, RheoScan-D. RESULTS: When treated with tBHP, the deformability of erythrocytes was decreased (P<0.01) and methemoglobin (metHb) formation and mean corpuscular volume (MCV) of erythrocytes were increased (P<0.01, P<0.05) compared to those of the untreated control cells. Compared to the tBHP treated cells, pretreatment with verapamil increased the deformability of erythrocytes (P<0.01) and decreased metHb formation (P<0.01) and MCV (P<0.05). Likewise, pretreatment with ascorbic acid increased the deformability of erythrocytes (P<0.01) and decreased metHb formation (P<0.01). CONCLUSIONS: Oxidative stress reduces the deformability of erythrocytes and the deformability could be one of markers for oxidative damage. Verapamil and ascorbic acid have protective role against tBHP induced oxidative stress. The ektacytometer, RheoScan-D used in this study is convenient for clinical measurement and could be used in various fields of clinical medicine.

Influence of pentoxifylline and dispirin on aggregation and deformability of erythrocytes under in vitro conditions.

Aggregation mechanism and deformability in pentoxifylline- and dispirin-treated erythrocytes are measured and compared with that of normal cells. The aggregation process is analyzed in terms of parameters which are obtained from the sequential recording of the transmitted light signal throughout the aggregate formation and sedimentation process. Erythrocyte deformability is determined by measurement of passage time through cellulose membrane. The variations in aggregation parameters in pentoxifylline-treated samples show that the formed aggregates are of larger size which sediment faster. In dispirin-treated cells, the formation of large size aggregates is delayed. The entire process is completed faster in pentoxifylline-treated compared to that of dispirin-treated cell whereas the normal sample shows an intermediate value. The deformability of erythrocytes treated with these drugs is increased.

Effect of vegetable oil intake on erythrocyte physical properties and hemorheology.

Effects of vegetable oil intake on red cell physical properties and blood flow condition were evaluated. The study was done on two groups of volunteers taking either soybean oil (6 volunteers) or palm oil (another 6 subjects) for a period of eight weeks. The continuous effects were followed up after continuing the vegetable oil intake for another four weeks. Significant reduction in red cell deformability was demonstrated by laser diffractometry in both groups. The palm oil had greater extent in causing reduced red cell deformability as early as four weeks after the oil intake, whereas, such effect was shown in eight weeks after the soybean oil intake. The reducing effect of red cell deformability by palm oil intake was more obvious than that by the soybean oil intake as indicated by the fall of deformability index from the control by 47.6 per cent in palm oil and 21.9 per cent in the soybean oil group. The decrease still persisted and could be investigated on the four weeks' followup. The hematologic parameters measured by the laser-based instrument, the H*1 analyser were all within the normal ranges in both groups. However, the group taking soybean oil showed decreasing hemoglobin levels, which may be a physiological response to facilitate blood flow condition. The platelet volume was increased in both groups, indicating the possibility of adjustment of thrombopoiesis in the subjects although no clinical indication related to this finding was shown. In conclusion, intake of vegetable oil had an effect on red cell deformability. Soybean oil had an advantage over palm oil in having less effect on reducing the red cell deformability.