The Effect of Glucose and Poloxamer 188 on Red-Blood-Cell Aggregation

Glucose metabolism disorders contribute to the development of various diseases. Numerous studies show that these disorders not only change the normal values of biochemical parameters but also affect the mechanical properties of blood. To show the influence of glucose and poloxamer 188 (P188) on the mechanical properties of a red-blood-cell (RBC) suspension, we studied the aggregation of the cells. To show the mechanisms of the mechanical properties of blood, we studied the effects of glucose and poloxamer 188 (P188) on red-blood-cell aggregation. We used a model in which cells were suspended in a dextran 70 solution at a concentration of 2 g/dL with glucose and P188 at concentrations of 0–3 g/dL and 0–3 mg/mL, respectively. RBC aggregation was determined using an aggregometer, and measurements were performed every 4 min for 1 h. Such a procedure enabled the incubation of RBCs in solution. The aggregation index determined from the obtained syllectograms was used as a measure of aggregation. Both the presence of glucose and that of P188 increased the aggregation index with the incubation time until saturation was reached. The time needed for the saturation of the aggregation index increased with increasing glucose and P188 concentrations. As the concentrations of these components increased, the joint effect of glucose and P188 increased the weakening of RBC aggregation. The mechanisms of the observed changes in RBC aggregation in glucose and P188 solutions are discussed.

Hemorheological Parameters in Diabetic Patients: Role of Glucose Lowering Therapies

Diabetes mellitus influences several important hemorheological parameters including blood viscosity, erythrocyte aggregation and deformability. In the present study, 159 type-2 diabetic patients and 25 healthy controls were involved. Patient’s age, body weight, body mass index (BMI), smoking habits, physical activity, history of cardiovascular diseases, current antidiabetic therapy and concomitant medication were recorded. Patients were grouped according to their antidiabetic treatment with insulin, or with one or more of the following antidiabetic drugs: metformin, sulfonylureas, acarbose, or no antidiabetic therapy. Hemorheological measurements (hematocrit, erythrocyte aggregation, plasma fibrinogen, whole blood and plasma viscosity), von Willebrand factor activity, and platelet aggregation measurements were performed. Platelet aggregation was investigated with the method of Born. Plasma viscosity and red blood cell aggregation were significatly higher in diabetes. No significant difference was found in hemorheological parameters between different antidiabetic regimens. Whole blood and plasma viscosity and red blood cell aggregation correlated with glucose levels but not with HbA1C levels. In conclusion, plasma and whole blood viscosity, as well as red blood cell aggregation appear to be associated with concurrent hyperglycemia, but not with the quality of glycemic control or the applied antidiabetic treatment. Platelet aggregation induced by ADP or epinephrine does not seem to be associated with diabetes even at subthreshold doses.

Numerical modelling of blood rheology and platelet activation through a stenosed left coronary artery bifurcation

Coronary bifurcations are prone to atherosclerotic plaque growth, experiencing regions of reduced wall shear stress (WSS) and increased platelet adhesion. This study compares effects across different rheological approaches on hemodynamics, combined with a shear stress exposure history model of platelets within a stenosed porcine bifurcation. Simulations used both single/multiphase blood models to determine which approach best predicts phenomena associated with atherosclerosis and atherothrombosis. A novel Lagrangian platelet tracking model was used to evaluate residence time and shear history of platelets indicating likely regions of thrombus formation. Results show a decrease in area of regions with pathologically low time-averaged WSS with the use of multiphase models, particularly in a stenotic bifurcation. Significant non-Newtonian effects were observed due to low-shear and varying hematocrit levels found on the outer walls of the bifurcation and distal to the stenosis. Platelet residence time increased 11% in the stenosed artery, with exposure times to low-shear sufficient for red blood cell aggregation (>1.5 s). increasing the risk of thrombosis. This shows stenotic artery hemodynamics are inherently non-Newtonian and multiphase, with variations in hematocrit (0.163–0.617) and elevated vorticity distal to stenosis (+15%) impairing the function of the endothelium via reduced time-averaged WSS regions, rheological properties and platelet activation/adhesion.

On the use of photoacoustics to detect red blood cell aggregation

The feasibility of detecting red blood cell (RBC) aggregation with photoacoustics (PAs) was investigated theoretically and experimentally using human and porcine RBCs. The theoretical PA signals and spectra generated from such samples were examined for several hematocrit levels and aggregates sizes. The effect of a finite transducer bandwidth on the received PA signal was also examined. The simulation results suggest that the dominant frequency of the PA signals from non-aggregated RBCs decreases towards clinical frequency ranges as the aggregate size increases. The experimentally measured mean spectral power increased by ~6 dB for the largest aggregate compared to the non-aggregated samples. Such results confirm the theoretical predictions and illustrate the potential of using PA imaging for detecting RBC aggregation.

On the use of photoacoustics to detect red blood cell aggregation

The feasibility of detecting red blood cell (RBC) aggregation with photoacoustics (PAs) was investigated theoretically and experimentally using human and porcine RBCs. The theoretical PA signals and spectra generated from such samples were examined for several hematocrit levels and aggregates sizes. The effect of a finite transducer bandwidth on the received PA signal was also examined. The simulation results suggest that the dominant frequency of the PA signals from non-aggregated RBCs decreases towards clinical frequency ranges as the aggregate size increases. The experimentally measured mean spectral power increased by ~6 dB for the largest aggregate compared to the non-aggregated samples. Such results confirm the theoretical predictions and illustrate the potential of using PA imaging for detecting RBC aggregation.

Numerical simulation of spatiotemporal red blood cell aggregation under sinusoidal pulsatile flow

Previous studies on red blood cell (RBC) aggregation have elucidated the inverse relationship between shear rate and RBC aggregation under Poiseuille flow. However, the local parabolic rouleaux pattern in the arterial flow observed in ultrasonic imaging cannot be explained by shear rate alone. A quantitative approach is required to analyze the spatiotemporal variation in arterial pulsatile flow and the resulting RBC aggregation. In this work, a 2D RBC model was used to simulate RBC motion driven by interactional and hydrodynamic forces based on the depletion theory of the RBC mechanism. We focused on the interaction between the spatial distribution of shear rate and the dynamic motion of RBC aggregation under sinusoidal pulsatile flow. We introduced two components of shear rate, namely, the radial and axial shear rates, to understand the effect of sinusoidal pulsatile flow on RBC aggregation. The simulation results demonstrated that specific ranges of the axial shear rate and its ratio with radial shear rate strongly affected local RBC aggregation and parabolic rouleaux formation. These findings are important, as they indicate that the spatiotemporal variation in shear rate has a crucial role in the aggregate formation and local parabolic rouleaux under pulsatile flow.