Aggregation Of Human Red Blood Cells Research Articles

Effects of amphiphilic star-shaped poly(ethylene glycol) polymers with a cholic acid core on human red blood cell aggregation

Elevated red blood cell (RBC) aggregation increases low-shear blood viscosity and is closely related to several pathophysiological diseases such as atherosclerosis, thrombosis, diabetes, hypertension, cancer, and hereditary chronic hemolytic conditions. Non-ionic linear polymers such as poly(ethylene glycol) (PEG) and Pluronic F68 have shown inhibitory effects against RBC aggregation. However, hypersensitivity reactions in some individuals, attributed to a diblock component of Pluronic F68, have been reported. Therefore, we investigated the use of an amphiphilic star-shaped PEG polymer based on a cholic acid core as a substitute for Pluronics to reduce RBC aggregation. Cholic acid is a natural bile acid produced in the human liver and therefore should assure biocompatibility. Cholic acid based PEG polymers, termed CA(PEG)4, were synthesized by anionic polymerization. Size exclusion chromatography indicated narrow mass distributions and hydrodynamic radii less than 2nm were calculated. The effects of CA(PEG)4 on human RBC aggregation and blood viscosity were investigated and compared to linear PEGs by light transmission aggregometry. Results showed optimal reduction of RBC aggregation for molar masses between 10 and 16kDa of star-shaped CA(PEG)4 polymers. Cholic acid based PEG polymers affect the rheology of erythrocytes and may find applications as alternatives to linear PEG or Pluronics to improve blood fluidity.

In vitro effects of polyethylene glycol in University of Wisconsin preservation solution on human red blood cell aggregation and hemorheology

Addition of hydroxyethyl starch (HES) to UW (University of Wisconsin) solution increases viscosity of the solution and red blood cell (RBC) aggregation. Recently, it was suggested that HES could be replaced by a new colloid, polyethylene glycol (PEG), in UW solution. The aim of this study was to see whether and how PEG affected RBC aggregation, and whether RBC aggregation parameters had any correlation with the molecular weight and concentration of PEG. After giving informed consent and signing consent documents, 12 healthy volunteers were enrolled in the study. Blood samples obtained from these volunteers were mixed with the test solutions with blood/solutions ratios of 5:1 and 1:1. Human RBC aggregation was investigated with an automatic hemorheological analyzer. Blood viscosity was measured with a cone-plate viscometer. Morphological characters of RBC aggregates were evaluated by light microscopy. It was found that viscosity was not affected by the Colloid-free UW solution. PEG20kDa (1 and 10 g/L) and PEG35kDa (1 g/L) had little effect on RBC aggregation, while PEG20kDa (30 g/L) and PEG35kDa (10 and 30 g/L) had a significant hyperaggregating effect on RBC. In conclusion, PEGs had a potential hyperaggregating effect on human RBC. This effect is correlated with PEG molecular weight and concentration. The use of large molecular weight and high concentration PEG in UW solution accounts for extended and accelerated aggregation of erythrocytes. The use of low concentration PEG35kDa (1 g/L) would be the optimal choice.

Effects of Polyethylene Glycol and Hydroxyethyl Starch in University of Wisconsin Preservation Solution on Human Red Blood Cell Aggregation and Viscosity

University of Wisconsin (UW) preservation solution is considered an effective flush and cold storage liquid. However, recent studies have provided evidence of the hyperaggregating effect on human red blood cells (RBC) of hydroxyethyl starch (HES), one of the components of the UW solution. In contrast, preservation solutions containing polyethylene glycol (PEG) have been found to be effective for organ preservation. The aim of this study was to compare the effects of HES (50 g/L); PEG 20 kDa (50 and 30 g/L), and PEG35 kDa (1.05 g/L) added to UW on the rheologic parameters of human RBC at 4°C. Sedimentation rate was measured by the Westergren procedure and blood viscosity evaluated at high shear rates using a cone/plate viscometer. Alterations in RBC morphology and aggregation were evaluated by light microscopy. RBC sedimentation and viscosity were not affected by the inversion of Na + and K + concentrations in UW, but were increased by HES. PEGs appeared to reduce RBC deformability with concomitant inhibition of RBC aggregation. These results were consistent with reduced viscosity for PEG-containing solutions. In conclusion, the use of PEG did not change the physiologic function of human RBCs and thus may be an alternative to HES in UW liquids.

Efficacy of Polyethylene Glycols in University of Wisconsin Preservation Solutions: A Study of Isolated Perfused Rat Liver

Recent reports argue that the performance of University of Wisconsin (UW) solution is limited by the presence of hydroxyethyl starch (HES) as an additive, since HES could be responsible for human red blood cell aggregation. We investigated the effect on rat liver preservation of replacing HES in UW solution by polyethylene glycols (PEG20 and PEG35) at two concentrations. An isolated perfused rat liver model was used. Six groups of preserved livers (n = 7 for each group) were compared to controls (nonpreserved livers, n = 7). The following preservation solutions were assayed: UW without oncotic supply, UW-HES (0.25 mmol/L), UW-PEG20 (0.03 and 0.25 mmol/L), and UW-PEG35 (0.03 and 0.25 mmol/L). After 24-hour cold storage, the livers were perfused for 120 minutes at 37°C with oxygenated Krebs-Henseleit solution. During perfusion, transaminase release, portal and bile flows, and bromosulfophthalein (BSP) clearance were assessed. Results showed that the omission of oncotic supply in UW statistically increased ALT and AST release in perfusate and decreased bile and portal flows. PEG addition in UW solution, especially PEG35 at 0.25 mmol/L, effectively protected the rat liver graft from the onset of hypothermic ischemia/reperfusion damage. In conclusion, data reported here reveal that oncotic supply is essential for liver preservation and that HES can be effectively replaced by PEG in UW solution.