Zhenze Wang

Nitric oxide transport in normal human thoracic aorta: effects of hemodynamics and nitric oxide scavengers.

Despite the crucial role of nitric oxide (NO) in the homeostasis of the vasculature, little quantitative information exists concerning NO transport and distribution in medium and large-sized arteries where atherosclerosis and aneurysm occur and hemodynamics is complex. We hypothesized that local hemodynamics in arteries may govern NO transport and affect the distribution of NO in the arteries, hence playing an important role in the localization of vascular diseases. To substantiate this hypothesis, we presented a lumen/wall model of the human aorta based on its MRI images to simulate the production, transport and consumption of NO in the arterial lumen and within the aortic wall. The results demonstrated that the distribution of NO in the aorta was quite uneven with remarkably reduced NO bioavailability in regions of disturbed flow, and local hemodynamics could affect NO distribution mainly via flow dependent NO production rate of endothelium. In addition, erythrocytes in the blood could moderately modulate NO concentration in the aorta, especially at the endothelial surface. However, the reaction of NO within the wall could only slightly affect NO concentration on the luminal surface, but strongly reduce NO concentration within the aortic wall. A strong positive correlation was revealed between wall shear stress and NO concentration, which was affected by local hemodynamics and NO reaction rate. In conclusion, the distribution of NO in the aorta may be determined by local hemodynamics and modulated differently by NO scavengers in the lumen and within the wall.

Comparative study of Newtonian and non-Newtonian simulations of drug transport in a model drug-eluting stent

To elucidate the difference between Newtonian and shear thinning non-Newtonian assumptions of blood in the analysis of DES drug delivery, we numerically simulated the local flow pattern and the concentration distribution of the drug at the lumen-tissue interface for a structurally simplified DES deployed in a curved segment of an artery under pulsatile blood flow conditions. The numerical results showed that when compared with the Newtonian model, the Carreau (shear thinning) model could lead to some differences in the luminal surface drug concentration in certain areas along the outer wall of the curved vessel. In most areas of the vessel, however, there were no significant differences between the 2 models. Particularly, no significant difference between the two models was found in terms of the area-averaged luminal surface drug concentration. Therefore, we believe that the shear thinning property of blood may play little roles in DES drug delivery. Nevertheless, before we draw the conclusion that Newtonian assumption of blood can be used to replace its non-Newtonian one for the numerical simulation of drug transport in the DES implanted coronary artery, other more complex mechanical properties of blood such as its thixotropic behavior should be tested.

Bioinspired helical graft with taper to enhance helical flow

Helical flow has been introduced to improve the hemodynamic performance of vascular devices such as arterial grafts, stents and arteriovenous shunts to overcome the flow induced thrombus formation and intimal hyperplasia. However, the quite low intensity of helical flow in the existing devices may limit their function. To obtain desirably high intensity, inspired by the helical flow and tapered configuration of the arterial system, we proposed a new conceptual design of the medical devices, which take the form of a tapered helical shape. We demonstrated its effectiveness in arterial grafts by numerically comparing the hemodynamic performance of helical grafts with different smooth tapers. The results show that the helicity density quantifying the helical flow enlarges sharply with the increase of the taper under both steady and pulsatile flow conditions. Moreover, the amplified helical flow induced by the taper would lead to highly elevated wall shear stress, remarkably reduced oscillating shear index and relative residence time at both the grafts and the anastomosis of the host vessel. The present findings therefore indicated that the new helical graft with taper would significantly enhance the helical flow in the grafts and host vessel, which may reduce the possibility of thrombus formation in the graft and intimal hyperplasia in the host vessel and hence improve the graft patency. In addition, the concept of helical shape with taper may also be applied to design arterial stents and arteriovenous shunts to obtain better hemodynamic performance.

Regional specific modulation of the glycocalyx and smooth muscle cell contractile apparatus in conduit arteries of tail-suspended rats

The glycocalyx is a key mechanosensor on the surfaces of vascular cells (endothelial cells and smooth muscle cells), and recently, we reported that the redistribution of the hemodynamic factors in tail-suspended (TS) hindlimb-unloaded rats induces the dimensional adaptation of the endothelial glycocalyx in a regional-dependent manner. In the present study, we investigated the coverage and gene expression of the glycocalyx and its possible relationship with smooth muscle contractility in the conduit arteries from the TS rats. The coverage of the glycocalyx, determined by the area analysis of the fluorescein isothiocyanate-labeled wheat germ agglutinin (WGA-FITC) staining to the cryosections of rat vessels, showed a 27.2% increase in the common carotid artery, a 13.3 and 8.0% decrease in the corresponding abdominal aorta and the femoral artery after 3 wk of tail suspension. The relative mRNA levels of syndecan-2, 3, 4, glypican-1, smooth muscle protein 22 (SM22), smoothelin (SMTN), and calponin were enhanced to 1.40, 1.53, 1.70, 1.90, 2.93, 2.30, and 5.23-fold, respectively, in the common carotid artery of the TS rat. However, both glycocalyx-related genes and smooth muscle contractile apparatus were totally or partially downregulated in the abdominal aorta and femoral artery of the TS rat. A linear positive correlation between the normalized coverage of glycocalyx and normalized mRNA levels of SM22, SMTN, and calponin exists. These results suggest the regional-dependent adaptation of the glycocalyx in simulated microgravity condition, which may affect its mechanotransduction of shear stress to regulate the contractility of the smooth muscle, finally contributing to postspaceflight orthostatic intolerance.

Influence of proximal drug eluting stent (DES) on distal bare metal stent (BMS) in multi-stent implantation strategies in coronary arteries.

The aim of this study was to investigate the drug distribution in arteries treated with DES-BMS stenting strategy and to analyze the influence of proximal DES on distal segments of BMS. A straight artery model (Straight Model) and a branching artery model (Branching Model) were constructed in this study. In each model, the DES was implanted at the proximal position and the BMS was implanted distally. Hemodynamic environments, drug delivery and distribution features were simulated and analyzed in each model. The results showed that blood flow would contribute to non-uniform drug distribution in arteries. In the Straight Model the proximal DES would cause drug concentration in BMS segments. While in the Branching Model the DES in the main artery has slight influence on the BMS segments in the branch artery. In conclusion, due to the blood flow washing effect the uniformly released drug from DES would distribute focally and distally. The proximal DES would have greater influence on the distal BMS in straight artery than that in branching artery. This preliminary study would provide good reference for atherosclerosis treatment, especially for some complex cases, like coronary branching stenting.

Influence of endoleak positions on the pressure shielding ability of stent-graft after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA)

BackgroundAbdominal aortic aneurysm (AAA) is a kind of dangerous aortic vascular disease, which is characterized by abdominal aorta partial enlargement. At present, endovascular aneurysm repair (EVAR) is one of the main treatments of abdominal aortic aneurysm. However for some patients after EVAR the aneurysm re-expanded and even ruptured, leading to poor postoperative effect. The stent-graft endoleak after EVAR was realized to influence the AAA in-sac pressure and contribute to the aneurysm re-enlargement.MethodsIn order to analyze the influence of endoleaks positions on the pressure shielding ability of stent-graft after EVAR, type I and type III endoleak models were reconstructed based on computed tomography (CT) scan images, and the hemodynamic environment in AAA was numerically simulated.ResultsWhen the endoleak was at the proximal position the pressure shielding ability will be obviously weakened. While, the pressure shielding ability was higher in the systole phase than that in diastole phase when the endoleak located at the middle or distal positions. Unfortunately, when the endoleak located at the proximal position, the pressure shielding ability would be relatively weak in the whole cardiac cycle.ConclusionsThe results revealed that the influence of endoleaks on pressure shielding ability of stent-graft was both location and time specific.

Enhanced Accumulation of LDLs within the Venous Graft Wall May Account for Its Accelerated Atherogenesis

To test the hypothesis that the venous graft when implanted in an arterial bypass might endure a fast infiltra-tion/accumulation of low-density lipoproteins (LDLs) within the vessel and hence the accelerated atherogenesis. we meas-ured measured DiI-LDLs uptake by both arteries and veins under arterial condition. The experimental results showed that that the amount of DiI-LDLs uptake by the venous wall was much higher compared with arterial wall, which was con-sistent with our hypothesis.

A NEW WAY TO OPTIMIZE DRUG RELEASE RATE OF DRUG ELUTING STENT (DES)

Local hemodynamic environment is a determinant factor in drug delivery from a drug eluting stent (DES) to the target arterial tissue. By using a simplified model of a DES, we demonstrated that if a DES had a drug release mode of uniform rate the drug released from the stent will distribute non-uniformly along the stent due to the flowing blood, with a significantly higher drug concentration at the distal part of the stent than that at the proximal one. This may explain why a DES could retard neointimal formation and vascular remodeling in downstream coronary segments. To solve this problem, we thereafter optimized the drug release mode of the DES as an exponential function. The simulation results showed that the optimized drug release mode could lead to a fairly uniform drug concentration distribution along the stent. Therefore, the present study suggested that to achieve a more effective result, optimization of drug eluting strategy (drug release mode) for the DES would be essential.