A Mathematical Model for Shear-Induced Platelet Activation in Response to Time Dependent Shear Stress Histories

Author(s):  
João S. Soares ◽  
Jawaad Sheriff ◽  
Danny Bluestein

The advent of blood recirculating devices and cardiovascular implants (e.g. ventricular assist devices and prosthetic heart valves) has motivated research efforts towards a better understanding of blood damage, hemolysis, and chronic platelet activation that these devices induce. Because of the latter, patients with these classes of implants still develop thromboembolic complications that expose them to a greater risk of cardioembolic stroke and mandate life-long anticoagulant drug regimen with its inherent risks.

Author(s):  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
João S. Soares ◽  
Jolyon Jesty ◽  
Danny Bluestein

Blood recirculating devices, which include ventricular assist devices and prosthetic heart valves, are necessary for some patients suffering from end-stage heart failure and valvular diseases. However, disturbed flow patterns in these devices cause shear-induced platelet activation and aggregation. Thromboembolic complications resulting from this platelet behavior necessitates lifelong anticoagulant therapy for patients implanted with such devices. In addition, blood recirculating device manufacturers mostly test and optimize their products for hemolysis, which occurs at shear stresses ten-fold higher than required for platelet activation. The relative paucity of optimization for flow-induced thrombogenicity is further exacerbated by the fact that there are few predictive shear-induced platelet activation models.


Author(s):  
Thomas E. Claiborne ◽  
Gaurav Girdhar ◽  
Jawaad Sheriff ◽  
Jolyon Jesty ◽  
Marvin J. Slepian ◽  
...  

Mechanical circulatory support (MCS) devices developed for end-stage heart failure or as a bridge-to-transplant include total artificial hearts (TAH) and ventricular assist devices (VAD) and utilize prosthetic heart valves (PHV) or rotary impellers to control blood recirculation [1]. These devices are currently not optimized to reduce the incidence of pathological flow patterns that cause elevated stresses leading to platelet activation and thrombosis. Although the latter is partially mitigated by lifelong anticoagulation therapy, it dramatically increases the risk of uncontrolled bleeding. For instance thromboembolic stroke-related complications (∼2%) were relatively less with the TAH-t compared to uncontrolled bleeding due to anticoagulation use (∼20%) [2]. Platelet activation should therefore be quantified and optimized based on patient-specific cardiac outputs in device prototypes before clinical use.


Author(s):  
J. Hanker ◽  
B. Giammara ◽  
J. Dobbins ◽  
W. DeVries

Implantation of the total artificial heart and its associated systems, such as the pneumatic driving system, or other cardiovascular prostheses such as ventricular assist devices, intravenous catheters, ventriculo-atrial shunts, pacemaker electrodes and prosthetic heart valves can be complicated by the problem of bacterial infection. Staphylococcus epidermidis. a ubiquitous commensal of human skin and mucous membranes normally does not cause disease in man. It is now recognized, however, as an opportunistic pathogen of biomaterial implants especially cardiovascular protheses. This is due to its ability to undergo transformation to produce mucoid or polysaccharide extracellular coating substances which promote its adherence to biomaterial surfaces and protect the bacteria against antibiotics and host defense mechanisms; this results in increased virulence of the slime-producing strains.


2012 ◽  
Vol 134 (8) ◽  
Author(s):  
Katharine H. Fraser ◽  
Tao Zhang ◽  
M. Ertan Taskin ◽  
Bartley P. Griffith ◽  
Zhongjun J. Wu

Ventricular assist devices (VADs) have already helped many patients with heart failure but have the potential to assist more patients if current problems with blood damage (hemolysis, platelet activation, thrombosis and emboli, and destruction of the von Willebrand factor (vWf)) can be eliminated. A step towards this goal is better understanding of the relationships between shear stress, exposure time, and blood damage and, from there, the development of numerical models for the different types of blood damage to enable the design of improved VADs. In this study, computational fluid dynamics (CFD) was used to calculate the hemodynamics in three clinical VADs and two investigational VADs and the shear stress, residence time, and hemolysis were investigated. A new scalar transport model for hemolysis was developed. The results were compared with in vitro measurements of the pressure head in each VAD and the hemolysis index in two VADs. A comparative analysis of the blood damage related fluid dynamic parameters and hemolysis index was performed among the VADs. Compared to the centrifugal VADs, the axial VADs had: higher mean scalar shear stress (sss); a wider range of sss, with larger maxima and larger percentage volumes at both low and high sss; and longer residence times at very high sss. The hemolysis predictions were in agreement with the experiments and showed that the axial VADs had a higher hemolysis index. The increased hemolysis in axial VADs compared to centrifugal VADs is a direct result of their higher shear stresses and longer residence times. Since platelet activation and destruction of the vWf also require high shear stresses, the flow conditions inside axial VADs are likely to result in more of these types of blood damage compared with centrifugal VADs.


Author(s):  
Gaurav Girdhar ◽  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
Yared Alemu ◽  
Thomas Claiborne ◽  
...  

Implantable blood recirculation devices such as ventricular assist devices (VADs) and more recently the temporary total artificial heart (TAH-t) are promising bridge-to-transplant (BTT) solutions for patients with end-stage cardiovascular disease. However, blood flow in and around certain non-physiological geometries, mostly associated with pathological flow around mechanical heart valves (MHVs) of these devices, enhances shear stress-induced platelet activation, thereby significantly promoting flow induced thrombogenicity and subsequent complications such as stroke, despite a regimen of post-implant antithrombotic agents. Careful characterization of such localized high shear stress trajectories in these devices by numerical techniques and corresponding experimental measurements of their accentuated effects on platelet activation and sensitization, is therefore critical for effective design optimization of these devices (reducing the occurrence of pathological flow patterns formation) for minimizing thrombogenicity [1].


Author(s):  
Thomas E. Claiborne ◽  
Wei-Che Chiu ◽  
Marvin J. Slepian ◽  
Danny Bluestein

Thrombotic complications, such as hemorrhage or embolism, remain a major concern of blood contacting medical devices [1], including prosthetic heart valves (PHV) and mechanical circulatory support devices, e.g. ventricular assist devices (VAD) or the Total Artificial Heart (TAH) [2]. In most cases device recipients require life-long anticoagulation therapy, which increases the risk of hemorrhagic stroke and other bleeding disorders. In order to obviate the need for anticoagulants and reduce stroke risks, our group developed a unique optimization methodology, Device Thrombogenicity Emulation (DTE) [2–5]. With the DTE, the thrombogenic potential of a device is evaluated using extensive numerical modeling and calculating multiple platelet trajectories flowing through the device. The platelet stress-time waveforms are then emulated in our Hemodynamic Shearing Device (HSD) and their activation level is measured with our Platelet Activation State (PAS) assay. This provides a proxy validation of the simulation. We identify high shear stress producing regions within the device and modify its design to reduce or eliminate those potentially thrombogenic ‘hot-spots.’ Through an iterative process, we can optimize the device design prior to prototyping.


1987 ◽  
Vol 110 ◽  
Author(s):  
J. J. Dobbins ◽  
B. L. Giammara ◽  
J. S. Hanker ◽  
P. E. Yates ◽  
W. C. DeVries

AbstractBacterial infection can be a problem associated with biomaterial implants especially with the total artificial heart or other cardiovascular prostheses such as ventricular assist devices, intravenous catheters, ventriculo-atrial shunts, pacemaker electrodes and, rarely, prosthetic heart valves. Bacterial commensals such as Staphylococcus epidermidis, which is ordinarily non-infective in human skin and mucous membranes, is now recognized as an opportunistic pathogen of biomaterial implants, particularly cardiovascular prostheses. In these implantations the S. epidermidis undergoes transformation to produce mucoid or polysaccharide extracellular coating substances. The latter promote bacterial adherence to biomaterial surfaces and protect the bacteria to some extent against antibiotics and host defense mechanisms. The result is increased virulence of the slime-producing strains. A number of techniques have been developed in our laboratories which facilitate identification of such bacterial pathogens on biopsy or postmortem specimens. These light and analytical electron microscopic methodologies include special cytochemical staining and rapid drying and embedding methods. Their efficacy and accuracy have been verified by studies on cultured and subcultured pathogens which are more time consuming. It is of interest that the microscopic methods showed the presence of macrophages as well as neutrophils on the specimens.


Author(s):  
Scott C. Corbett ◽  
Ahmet U. Coskun ◽  
Hamid N-Hashemi

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.


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