Date Published: January 24, 2019
Publisher: Public Library of Science
Author(s): Hyeonji Hong, Jae Min Song, Eunseop Yeom, Adélia Sequeira.
In studying blood flow in the vessels, the characteristics of non-Newtonian fluid are important, considering the role of viscosity in rheology. Stenosis, which is an abnormal narrowing of the vessel, has an influence on flow behavior. Therefore, analysis of blood flow in stenosed vessels is essential. However, most of them exist as simulation outcomes. In this study, non-Newtonian fluid was observed in stenosed microchannels under the pulsatile flow condition. A polydimethylsiloxane channel with 60% stenosis was fabricated by combining an optic fiber and a petri dish, resembling a mold. Three types of samples were prepared by changing the concentrations of xanthan gum, which induces a shear thinning effect (phosphate buffered saline (PBS) solution as the Newtonian fluid and two non-Newtonian fluids mimicking normal blood and highly viscous blood analog). The viscosity of the samples was measured using a Y-shaped microfluidic viscometer. Thereafter, velocity profiles were analyzed under the pulsatile flow condition using the micro-particle image velocimetry (PIV) method. For the Newtonian fluid, the streamline was skewed more to the wall of the channel. The velocity profile of the non-Newtonian fluid was generally blunter than that of the Newtonian fluid. A highly oscillating wall shear stress (WSS) during the pulsatile phase may be attributed to such a bluntness of flow under the same wall shear rate condition with the Newtonian fluid. In addition, a highly viscous flow contributes to the variation in the WSS after passing through the stenosed structures. A similar tendency was observed in simulation results. Such a variation in the WSS was associated with plaque instability or rupture and damage of the tissue layer. These results, related to the influence on the damage to the endothelium or stenotic lesion, may help clinicians understand relevant mechanisms.
Since the characteristics of pulsatile blood flow in the vessels are complex and unsteady, it is not easy to comprehend hemodynamic features completely.[1, 2] To understand blood flow, studies using Newtonian fluids, such as mixtures of glycerol and water models, have been widely conducted.[3–8] The results on Newtonian fluids may be reasonable for large-scale channels mimicking arteries. However, the non-Newtonian behavior of the blood increases the viscosity at a low shear strain rate.[9, 10] Blood viscosity influences flow resistance, and an increased viscosity is a biological parameter related to cardiovascular disease. Therefore, Newtonian blood flow may insufficiently illustrate actual cardiovascular flow at low shear rate regions, such as downstream of stenosis in small-diameter vessels.
To identify the viscosity of the three working fluid samples, a Y-shaped microchannel proposed in a previous study was used. As shown in Fig 2A, the Y-shaped channel was composed of two inlets and one outlet. The downstream of the channel has a 3000-μm width and 50-μm height. The reference fluid and sample were delivered by syringe pumps into each inlet of the channel. The interfacial line was developed behind the junction of the Y-shaped microchannel where the two fluids meet. The flow image including an interfacial line (region of interest) was captured using a high-speed camera connected with the microscope. Fig 2A presents the actual images when the flow rates of the reference fluid and sample were fixed at 3.5 mL/h and 1.0 mL/h, respectively. The width ratio between the sample and reference fluid was determined by the pressure ratio determined by the flow rate and the viscosity of the fluids.
The velocity profile of the Newtonian fluid was skewed toward the wall at the opposite side of the stenosed wall; such a skewness was not as intense in the non-Newtonian fluids. These findings imply that a Newtonian fluid can be easily skewed by geometric structures because its pressure loss is higher than that of a non-Newtonian fluid under the same flow condition in the curved geometry.[1, 12] Nevertheless, the shear thinning fluid was influenced by the stenosed structure. As shown in Fig 8, the velocity profile did not tend to be much skewed but seemed to be blunter at the post-stenosis region, since the pressure drop from upstream to downstream was smaller in the non-Newtonian model. Furthermore, the kinetic energy at the post-stenosis region drops owing to the effect of viscosity.[12, 25] From that, the bluntness is associated with the increase in blood viscosity, while the profile has a relatively high velocity at the vessel wall. The velocity profile arising from the increased viscosity can alter the flow resistance because the frictional force can hinder RBCs from moving.[38, 39] Moreover, it may induce production of cholesterol and low-density lipoproteins.[11, 40] In Fig 7, the non-Newtonian fluids having a higher viscosity showed blunter shapes also at the stenotic apex than the Newtonian fluid. Therefore, for highly viscous fluids, a relatively high WSS around the stenosis region may be attributed to such a bluntness of flow under the same WSR condition with Newtonian fluids (Fig 10). A high WSS is associated with an increased risk of fibrous cap rupture. Therefore, plaque remodeling may occur owing to a high WSS, which can result in acute coronary syndrome from rupture of the cap.[42–44]
Through the experiment and simulation, the velocity profiles and WSS variations were observed in the stenosed microchannel along the phases of pulsatile flow using both Newtonian and non-Newtonian fluids. The blood analog flow can be affected by pulsatile flows and stenosed shapes. Such fluctuations may be related to potential heart attacks.[19, 25] Moreover, the increase in the WSS and the oscillating WSS in highly viscous fluids can damage the blood cells, endothelium, or stenotic lesions, since it is relevant to endothelial cell morphology and nitric oxide production.[25, 52–54] While this study cannot directly explain the mechanism related to vascular pathology, the lesion is associated with WSS and flow behavior caused by stenotic structure and pulsatile flow with regard to viscosity variations in blood analog fluids.