Scott C. Corbett

In Vitro and Computational Thrombosis on Artificial Surfaces With Shear Stress

Implantable devices in direct contact with flowing blood are associated with the risk of thromboembolic events. This study addresses the need to improve our understanding of the thrombosis mechanism and to identify areas on artificial surfaces susceptible to thrombus deposition. Thrombus deposits on artificial blood step transitions are quantified experimentally and compared with shear stress and shear rate distributions using computational fluid dynamics (CFD) models. Larger steps, and negative (expanding) steps result in larger thrombus deposits. Fitting CFD results to experimental deposit locations reveals a specific shear stress threshold of 0.41 Pa or a shear rate threshold of 54 s(-1) using a shear thinning blood viscosity model. Thrombosis will occur below this threshold, which is specific to solvent-polished polycarbonate surfaces under in vitro coagulation conditions with activated clotting time levels of 200-220 s. The experimental and computational models are valuable tools for thrombosis prediction and assessment that may be used before proceeding to clinical trials and to better understand existing clinical problems with thrombosis.

Effect of pulsatile blood flow on thrombosis potential with a step wall transition.

It is well known that thrombus can be formed at stagnation regions in blood flow. However, studies of thrombus formation have typically focused on steady state flow. We hypothesize that pulsating flow may reduce persistent stagnation at the sites of low shear stress by decreasing exposure time. In this study, a step-wall transition, which is commonly found on implantable devices, is used as a test bed causing a recirculation vortex. Stagnation at such a step is considered using computational fluid dynamics studies and flow visualization experiments. Parametric studies were performed with varying step height, pulsatility, and velocity. The percentage of time along the wall with shear stresses below a threshold for thrombosis and the total length of wall that maintains contact with stagnant flow throughout the cardiac cycle are calculated. Persistent stagnation occurs at the corner of a step-wall transition in all cases and is observed to decrease with a decrease in step height, an increase in mean velocity, and an increase in pulsatility. Under steady flow conditions, a flow reattachment point resulting from recirculation is observed with expanding steps, whereas a flow separation point is observed with contracting steps. Pulsatility decreases persistent stagnation at the flow separation point with contracting steps, whereas it completely eliminates persistent stagnation at the flow reattachment point with expanding steps. The results of this work conclusively show that stagnation can be reduced by increasing pulsatility and flow velocity and by decreasing step height.

Effects of fluid flow shear rate and surface roughness on the calcification of polymeric heart valve leaflet.

Surface defects, blood flow shear rates and mechanical stresses are contributing factors in the calcification process of polymeric devices exposed to the blood flow. A number of experiments were performed to evaluate the effect of surface defects such as roughness and cracks and flow shear rate on the calcification process of a polyurethane material used in the design of prosthetic heart valves. Results showed that polyurethane surface gets calcified and the calcification is more pronounced at the lower shear rates. Roughness and cracks both increase the calcification levels. The results also suggest very little diffusion of calcium to the subsurface indicating that calcification of a polyurethane material, is a surface phenomenon. Based on a simple peeling test, the bond strength between the calcified layer and polyurethane was found to be extremely weak, suggesting that the bonding is in the form of Van-der-Waals. A limited set of experiments with polycarbonate showed that polycarbonate is less prone to calcification compared to polyurethane (p values less than 0.05), indicating its potential application in medical devices exposed to blood flow.

Effect of Blood Viscosity on Thrombosis Potential Near a Step Wall Transition

Thrombosis and hemolysis are two problems encountered when processing blood in artificial organs. Physical factors of blood flow alone can influence the interaction of proteins and cells with the vessel wall, induce platelet aggregation and influence coagulation factors responsible for the formation of thrombus, even in the absence of chemical factors in the blood. These physical factors are related to the magnitude of the shear rate/stress, the duration of the applied force and the local geometry. Specifically, high blood shear rates (or stress) lead to damage (hemolysis, platelet activation), while low shear rates lead to stagnation and thrombosis [1].Copyright

Regurgitant Commissure Flow Through a Closed Polymeric Heart Valve

While heart valve prostheses have been used successfully since 1960, outcomes are far from ideal. The underlying problem with bioprostheses is a limited life from structural changes such as calcification and leaflet wear, leading to valve failure. The underlying problem with mechanical heart valves is the presence of flow disturbances which necessitate anticoagulation. A polyurethane valve has the potential to improve upon the shortcomings of existing valves and ultimately improve patient survival.© 2010 ASME

Calcification of Trileaflet Polyurethane Heart Valve

Heart valve disease is a common type of cardiac disease that causes a large number of mortalities worldwide. Patients with severe heart valve problems are required to undergo heart valve replacement surgeries. Mechanical and bioprosthetic heart valves are the current available prostheses for patients in need of a heart valve replacement surgery. Mechanical heart valves are susceptible to thromboembolism and thrombosis and bioprosthetic valves have a limited life-span because of leaflet wear and calcification. Different polyurethane valves were suggested as an alternative material. However, prior results indicated that tested polyurethanes failed due to calcification. The mechanism for polyurethane calcification is not yet completely understood. Kou Imachi et al. [2], suggested that the calcification is due to entrapment of blood proteins and/or phospholipids in microgaps in the polymer and subsequent attraction of Ca ion, leading to formation of calcium phosphate (Ca3(PO4)2). Bisphosphonates (BP), which are considered to enhance the calcification resistance of polymers once covalently bonded to the material, indicated promising results in some studies. Focus of the present study is the trileaflet polyurethane valve, originally developed in the design of the AbioCor® replacement heart, and has demonstrated excellent durability and hemocompatibility in clinical evaluation. Over the past three years, this valve has been modified and its potential as a replacement valve have been studied [1]. Valve hemodynamic analysis showed that it is comparable to bioprosthetic valve in terms of fluid flow, pressure drop and regurgitation [1]. In order to ensure the suitability of the trileaflet polyurethane valve as a replacement valve its fatigue and calcification resistance are studied. The purpose of this paper is to simulate calcification of trileaflet polyurethane valves in an in vitro accelerated test and compare that with that of tissue valves. Furthermore the effect of bisphosphonate modified polyurethane on calcification is studied.Copyright

Characterization of a Novel Polymeric Trileaflet Heart Valve Prosthesis

While heart valve prostheses have been used successfully since 1960, 10-year survival rates still range from 37–58% [1]. The underlying problem with bioprostheses is a limited life from structural changes such as calcification and leaflet wear, leading to valve failure [2]. Biological tissue fixation and methods used to mount the tissue to a supporting stent can be blamed for this shortcoming. The underlying problem with mechanical heart valves is the presence of a centrally located leaflet, or occluder. It propagates high velocity jets, turbulence and areas of stagnation: the disturbances which necessitate anticoagulation [3]. A polyurethane valve has the potential to improve upon the shortcomings of existing valves and ultimately improve patient survival.Copyright

Simulation of Pulsatile Blood Flow With a Wall Step Transition

Implantable devices in direct contact with flowing blood, for example, coronary stents, continuous flow and pulsatile flow ventricular assist devices, prosthetic heart valves, catheters and cannulae are currently being used to treat many medical conditions. However, thromboembolism and the attendant risk for ischemic stroke remains an impediment for all these devices. A prudent approach to developing these devices in a cost effective manner should include optimization for thrombogenic performance before going into expensive preclinical and clinical trials.Copyright

Simulation of Pulsatile Blood Flow Through a Flexible Cannula

Implantable devices in direct contact with flowing blood are currently being used to treat many medical conditions; however, thromboembolism, blood damage and the attendant risk for ischemic stroke remains a major impediment. Specifically, vascular access methods, performed by the insertion of cannulae into vessels, may give rise to non-physiological pressure variations and shear stresses. To date, the hydrodynamic behavior of cannulae has been evaluated by comparing their pressure loss-flow rate relationships, as obtained from in vitro experiments. Numerical studies have evaluated cannulae as rigid wall vessels with steady flow conditions [1]. Various catheter tip styles have been compared [2], and the fluid dynamics of arterial cannulae inserted in the aortic arch have been investigated [3]. Evaluation of shear stresses within a flexible wall cannula under pulsatile blood flow conditions is discussed herein. We anticipate that considerations for pulsating blood flow and flexible device walls will indicate that anticoagulation requirements can be minimized and device related complications can be decreased, thus increasing patient survival rates.Copyright