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Many people are sensitive to cold, resulting in poor blood circulation. There is evidence that hesperidin results in increased peripheral circulation and skin temperature. A transglycosylated hesperidin, α-glucosylhesperidin, is more bioabsorbable than hesperidin. In the present study, biomechanical studies were performed on the effects of long-term feeding of α-glucosylhesperidin on the contractile response (diameter response) and stiffness of femoral arteries excised from rabbits. Animals in the normal (non-treated), low, and high groups were fed 0, 150 and 4500 mg/day, respectively, of α-glucosylhesperidin for about 24 weeks. The feeding of α-glucosylhesperidin did not change arterial stiffness nor mean blood flow rate in the femoral artery; however, it increased mean aortic blood pressure and decreased arterial diameter at 100 mmHg in the high group. The diameter responses developed by 10-5 M of norepinephrine were significantly lower in the high and low groups than in non-treated group. This result indicates that, due to the long-term feeding of α-glucosylhesperidin, arterial contraction induced by the neurotransmitter of sympathetic nerves decreases. It was estimated that blood flow in such muscular arteries as the femoral artery is maintained at normal by α-glucosylhesperidin even under the conditions of autonomic imbalance and cold intolerance.

To substantiate the occurrence of flow-dependent concentration or depletion of atherogenic lipoproteins, which has been theoretically predicted to take place at a blood/endothelium boundary, we have studied the effects of perfusion pressure and wall shear rate on the accumulation and uptake of microspheres by cultured vascular endothelial cells in a monolayer. The study was carried out by flowing a cell culture medium containing fetal calf serum and fluorescent microspheres through a parallel-plate flow chamber having a cultured bovine aortic endothelial cell (BAEC) monolayer on one wall of the chamber. The microspheres had a nominal diameter of 19 nm, approximately the same as that of low-density lipoproteins, and thus served as models and tracers of plasma proteins and lipoproteins. Experiments were carried out in steady flow in the physiological range of wall shear rate and water filtration velocity at the monolayer, while monitoring the intensity of fluorescence of the spheres accumulated at and taken up by the endothelial cells. It was found that in a perfusate containing only fluorescent microspheres, due to increased phagocytic activity of the endothelial cells, the intensity of fluorescence which reflected the number of the microspheres taken up by the endothelial cells, increased almost linearly with time and independently of wall shear rate. However, with perfusates containing fetal calf serum, this abnormal phenomenon did not occur, and the intensity of fluorescence increased with increasing perfusion pressure and decreasing wall shear rate. It was also found that the number of fluorescent microspheres accumulated at and taken up by the BAEC monolayer was shear-dependent only at low wall shear rates, and increased sharply when the flow rate was reduced to zero. These results provided solid experimental evidence that flow-dependent concentration or depletion of macromolecules occurs at the luminal surface of the endothelium at physiological wall shear rates and water filtration velocities, and strongly supports the hypothesis that flow-dependent concentration polarization of lipoproteins plays an important role in the localization of atherosclerosis and intimal hyperplasia in man by facilitating the uptake of atherogenic lipoproteins by endothelial cells.

Flow-dependent concentration or depletion of atherogenic low density lipoproteins which has been theoretically predicted to occur at a blood/endothelium boundary may play an important role in the genesis, progression, and regression of atherosclerosis in man and intimal hyperplasia in vascular grafts implanted in the arterial system in man and experimental animals. Hence to explore such a possibility, we have studied the effect of a steady shear flow on concentration polarization of plasma proteins and lipoproteins at the luminal surface of a cultured bovine aortic endothelial cell (BAEC) monolayer which served as a model of the vessel wall of an artery or an implanted vascular graft. The study was carried out by circulating a cell culture medium containing fetal calf serum or bovine plasma lipoproteins in steady flow through a parallel-plate flow cell in which a cultured BAEC monolayer was installed, over the physiologic ranges of wall shear rate and water filtration velocity at the BAEC monolayer. The water (cell culture medium) filtration velocity at the BAEC monolayer was determined to provide a measure of the change in concentration of plasma protein particles at the luminal surface of the BAEC monolayer. It was found that for perfusates containing plasma proteins and/or lipoproteins, water filtration velocity varied as a function of flow rate, being lowest in the absence of flow. Water filtration velocity increased or decreased as flow rate increased or decreased from an arbitrarily set non-zero value, indicating that surface concentration of protein particles varied as a direct function of flow rate, and the process was reversible. It was also found that at particle concentrations equivalent to those found in a culture medium containing serum at 20% by volume, plasma lipoproteins which were much smaller in number and lower in concentration but larger in size than albumin, showed almost the same effect as observed with serum which contained both lipoproteins and albumin, indicating that the substance responsible for this phenomenon is not albumin but lipoprotein whose diffusivity is much smaller than that of albumin. The results strongly support our hypothesis that flow-dependent concentration polarization of lipoproteins occurs at a blood endothelium boundary, and this in turn promote the localization of various vascular diseases which develop in our arterial system.

The effect of steady shear flow on concentration polarization of plasma proteins and lipoproteins at the luminal surface of a semipermeable vessel wall was studied experimentally using suspensions of these molecules in a cell culture medium and a semipermeable membrane dialysis tube which served as a model of an implanted vascular graft or an artery. The study was carried out by flowing a cell culture medium containing fetal calf serum or bovine plasma lipoproteins or bovine albumin through a 7.5 mm diameter, 60 mm-long dialysis tube in steady flow under a physiologic mean arterial perfusion pressure of 100 mmHg, and measuring the filtration velocity of water (cell culture medium) at the vessel wall which varied as a consequence of the change in concentration of plasma protein particles at the luminal surface of the semipermeable membrane dialysis tube. It was found that for perfusates containing plasma proteins and/or lipoproteins, filtration velocity of water was the lowest in the absence of flow, and it increased or decreased as the flow rate (hence wall shear rate) increased or decreased from a certain non-zero value, indicating that surface concentration of protein particles varied reversibly as a direct function of flow rate. It was also found that at particle concentrations equivalent to those found in a culture medium containing serum at 5% by volume, plasma lipoproteins which were much smaller in number and lower in concentration but larger in size than albumin, had a much larger effect on the filtration velocity of water than albumin. These findings were very much the same as those previously obtained with a cultured endothelial cell monolayer, strongly suggesting that the flow-dependent variation in filtration velocity of water at a vessel wall results from a physical phenomenon, that is, flow-dependent concentration polarization of low density lipoproteins at the luminal surface of the endothelial cell monolayer.

The structure of pulsatile flow in a rigid aortic bifurcation model was studied by means of a flow visualization technique and three-dimensional laser-Doppler anemometry. The model was made of glass, having the same shape as that of the average human aortic bifurcation. It was installed into a mock circulatory loop that generated physiological pulsatile flow. Flow separation was observed during accelerated and decelerated flow periods. Double helical flow existed inside the flow separation in the early accelerated flow period. In the decelerated flow period, disturbed flow appeared behind the separation zone. Flow was strongly disturbed during the back flow period, and then was gradually stabilized in the forward flow period. The flow separation and the disturbances released from the flow separation zone greatly influenced near-wall velocities along the lateral wall. The wave form of the near-wall velocity in the flow separation zone was much different from that observed in the aortic portion and behind the separation zone; for example, the magnitude of the negative peak velocity in the direction of the tube axis was larger than that of the positive one, and mean velocity in a cycle was very low. This abnormal phasic change of the near-wall velocity may be associated with atherogenesis. The three-dimensional velocity measurement is very useful for the detailed analysis of near-wall velocity patterns.

Effects of wall compliance on the flow characteristics were studied by visualizing pulsatile flow in two straight elastic tubes having different compliance and in a rigid tube. The elastic tubes were made of segmented polyether polyurethane and their compliance was adjusted by varying the wall thickness. Their diameter changes were +/- 3.3 and +/- 4.9% for the pressure pulsation between 20 and 250 mm Hg. An acrylic pipe was used for the rigid model. An air-driven artificial heart was used to generate the pulsatile flow having the mean Reynolds number and frequency parameter of 740 and 11.4, respectively. The flow was visualized by the hydrogen bubble method at every 5% of the pulsatile flow cycle. Velocity distributions along the tube diameter were determined from still images of time lines taken with a CCD camera. The ratio of the wall shear rate in the elastic tubes to that in the rigid tube at each phase correlated well with the radial velocity of tube wall, while it had no significant correlation with the instantaneous tube diameter. These results suggest that the wall compliance either increases or decreases the wall shear rate depending on the phasic relation between the flow and pressure waves. When studying the hemodynamic effects on vascular diseases by model experiments, it may be important to take wall elasticity into account.

Flow characteristics near the end-to-end anastomosis of vascular graft were studied in model tubes by flow visualization techniques. Artery and vascular graft were modelled by an elastic tube fabricated from an elastomeric polymer and a rigid plastic tube, respectively. Anastomotic models were made by connecting these two tubes, which had compliance mismatch at their anastomoses. These model tubes were installed into a mock circulatory loop and flow was visualized using hydrogen bubbles and aluminum powder as the tracer. Flow disturbances including flow separation and eddies were observed near the modelled distal anastomosis (graft-to-artery anastomosis). Peak values of the wall shear rate were high in the proximal anastomotic area (artery-to-graft anastomosis) and low in the distal region. These phenomena were enhanced in the models with increased compliance mismatch. The local abnormal flow observed in the anastomotic zone might cause thrombus formation and subintimal hyperplasia. To improve the patency in small-calibered arterial grafts, it is important to match their compliance to that of natural arteries.