Evaluation of Platelet Activation Models With Dynamic Shear Stress In Vitro Experiments

2012 ◽  
Author(s):  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
João S. Soares ◽  
Jolyon Jesty ◽  
Danny Bluestein
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Ventricular Assist Devices ◽  
Prosthetic Heart Valves ◽  
Shear Stresses ◽  
Ventricular Assist ◽  
Relative Paucity ◽  
Valvular Diseases ◽  
End Stage

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.

Dynamic Shear Stress Induced Platelet Activation in Blood Recirculation Devices: Implications for Thrombogenicity Minimization

2009 ◽  
Author(s):  
Gaurav Girdhar ◽  
Jawaad Sheriff ◽  
Michalis Xenos ◽  
Yared Alemu ◽  
Thomas Claiborne ◽  
...  
Keyword(s):  
Shear Stress ◽  
Platelet Activation ◽  
Heart Valves ◽  
Total Artificial Heart ◽  
Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Bridge To Transplant ◽  
End Stage ◽  
Effective Design

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].

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

2012 ◽  
Author(s):  
João S. Soares ◽  
Jawaad Sheriff ◽  
Danny Bluestein
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Drug Regimen ◽  
Ventricular Assist Devices ◽  
Prosthetic Heart Valves ◽  
Thromboembolic Complications ◽  
Ventricular Assist ◽  
Blood Damage ◽  
Anticoagulant Drug ◽  
Cardiovascular Implants

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.

In Vitro Evaluation of Shear-Induced Platelet Activation in the MicroMed DeBakey Ventricular Assist Device With Antiplatelet Therapy

2013 ◽  
Author(s):  
Jawaad Sheriff ◽  
Gaurav Girdhar ◽  
Sheela George ◽  
Wei-Che Chiu ◽  
Bryan E. Lynch ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thrombus Formation ◽  
Optimization Techniques ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Ventricular Assist ◽  
Bridge To Transplant ◽  
Thrombotic Complications ◽  
End Stage

Mechanical circulatory support (MCS) devices, which include ventricular assist devices (VADs), offer an attractive solution to approximately 35,000 end-stage heart failure patients eligible for transplants, of which only 2,000–2,300 are performed annually [1]. These devices are employed to augment the function of the ailing left and/or right ventricle and serve as bridge-to-transplant or destination therapy, but are often accompanied by thrombotic complications. Pathologic flow patterns are characteristic of VADs and increase susceptibility to shear-induced platelet activation, which leads to thrombus formation [2]. Patients implanted with such devices are routinely prescribed antiplatelets to tackle these complications. Despite this concurrent therapy, thromboembolic incident rates of 0.9–13% are reported for the widely-implanted Thoratec HeartMate II and MicroMed DeBakey VADs [3, 4]. This has spurred the development of design optimization techniques to lower or eliminate the incidence of thrombosis and reduce the dependence on pharmacotherapy management.

Design Optimization of Rotary Blood Pumps: Alternatives to Anticoagulation Therapy

2011 ◽  
Author(s):  
Gaurav Girdhar ◽  
Michalis Xenos ◽  
Wei-Che Chiu ◽  
Yared Alemu ◽  
Bryan Lynch ◽  
...  
Keyword(s):  
Heart Valves ◽  
Anticoagulation Therapy ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Shear Stresses ◽  
Ventricular Assist ◽  
Bridge To Transplant ◽  
Life Saving ◽  
Optimization Methodology ◽  
Rotary Blood Pumps

Mechanical circulatory support (MCS) devices such as the ventricular assist devices (VADs) provide life saving short-term bridge-to-transplant solutions (1) to a large proportion of patients who suffer from chronic heart failure. Although hemodynamically efficient, such devices are burdened with high incidence of thromboembolic events due to non-physiological flow past constricted geometries where platelets (the principal cellular clotting elements in blood) are exposed to elevated shear stresses and exposure times (2) — requiring mandatory anticoagulation. We recently developed an optimization methodology — Device Thrombogenicity Emulator (DTE)(3) — that integrates device specific hemodynamic stresses (from numerical simulations) with experimental measurements of platelet activation. The DTE was successfully applied by our group to measure / optimize the thromboresistance of mechanical heart valves (MHV) (3, 4).

Platelet Activation and Free Emboli Formation in Flow Past Mechanical Heart Valves

2002 ◽  
Author(s):  
Danny Bluestein ◽  
Wei Yin ◽  
Jolyon Jesty ◽  
Adam E. Saltman ◽  
Irvin B. Krukenkamp ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Heart Valves ◽  
Left Ventricular ◽  
Mechanical Heart Valves ◽  
Shear Stresses ◽  
Platelet Activity ◽  
Flow Past ◽  
Activity State ◽  
Valve Implantation

Numerical studies, in vitro, and in vivo measurements were conducted, aimed at quantifying free emboli formation and procoagulant properties of platelets induced by flow past mechanical heart valves (MHV). Pulsatile turbulent flow simulation was conducted past a St. Jude medical MHV in the aortic position, to study the effects of valve implantation technique on the thromboembolic potential of the valve. A misaligned valve with subannualarly sutured pledgets produced accelerating jet flow through the valve orifices and a wider wake of shed vortices. Shear stress histories of platelets along turbulent trajectories exposed the platelets to elevated shear stresses around the leaflets, leading them to entrapment within the shed vortices. In vitro platelet studies were conducted past the MHV mounted in a recirculation flow loop and in a model of left ventricular assist device (LVAD), using an innovative platelet activity state (PAS) assay. The platelet activation significantly increased as a function of the recirculation time past the valve, and as compared to controls. Transcranial Doppler (TCD) measurements were conducted in the carotid artery of sheep with implanted MHV, showing marked increase in the number of HITS (High Intensity Transient Signals) signifying the passage of free emboli generated by the valve. The HITS were analyzed to distinguish between gaseous and thrombi emboli. Finally, platelet activity state measurements were conducted with sheep platelets, showing marked increase of platelet activation after valve implantation.

In-Vitro Thrombogenicity Assessment of Mechanical Circulatory Support Devices and Prosthetic Heart Valves

2010 ◽  
Author(s):  
Thomas E. Claiborne ◽  
Gaurav Girdhar ◽  
Jawaad Sheriff ◽  
Jolyon Jesty ◽  
Marvin J. Slepian ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Mechanical Circulatory Support ◽  
Heart Valves ◽  
Anticoagulation Therapy ◽  
Ventricular Assist Devices ◽  
Patient Specific ◽  
Circulatory Support ◽  
Prosthetic Heart Valves ◽  
Bridge To Transplant ◽  
Uncontrolled Bleeding

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.

The cytochemical demonstration of bacteria in total artificial heart implant specimens

1987 ◽  
Vol 45 ◽  
pp. 778-779 ◽  
Author(s):  
J. Hanker ◽  
B. Giammara ◽  
J. Dobbins ◽  
W. DeVries
Keyword(s):  
Defense Mechanisms ◽  
Artificial Heart ◽  
Heart Valves ◽  
Opportunistic Pathogen ◽  
Total Artificial Heart ◽  
Ventricular Assist Devices ◽  
Prosthetic Heart Valves ◽  
Ventricular Assist ◽  
Cytochemical Demonstration ◽  
Biomaterial Surfaces

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.

Implementation of an Automated Peripheral Resistance Device in a Mock Circulatory Loop With Characterization of Performance Values Using Simulink Simscape and Parameter Estimation

2012 ◽  
Vol 6 (4) ◽  
Author(s):  
Charles E. Taylor ◽  
Gerald E. Miller
Keyword(s):  
Parameter Estimation ◽  
Heart Valves ◽  
Water Solution ◽  
Peripheral Resistance ◽  
Ventricular Assist Devices ◽  
Experimental Conditions ◽  
Ventricular Assist

Accurate peripheral resistance simulation in a mock circulatory loop is critical to the evaluation of ventricular assist devices and heart valves. Implementation of an automated device that is capable of accurate resistance settings and precise reproduction of cardiovascular parameters allows for improved construction of experimental conditions within a mock circulatory loop. A mock circulatory loop resistor that employs a proportional valve design is proposed; a piston extending into the flow path to produce a resistance to flow. Real-time position feedback of the piston is used to determine orifice size, providing resolution in the change of resistance over time. Characterization of the physical system with The MathWorks SIMULINK™ SIMSCAPE™ block set allowed the determination of objective device parameters; the discharge coefficient and critical Reynolds number. The determination of these values was achieved utilizing the SIMULINK™ Parameter Estimation™ tool, experimental data, and a computational plant model of the experimental setup. With this information, an accurate computational model of the resistance device is presented for use in determining resistance settings in silico prior to implementation in the mock circulatory loop. Experimental in vitro trials verified the repeatability of the automated resistor performance by means of a staircase testing of piston position during several different continuous flow rates of a glycerin/water solution.

scholarly journals A Quantitative Comparison of Mechanical Blood Damage Parameters in Rotary Ventricular Assist Devices: Shear Stress, Exposure Time and Hemolysis Index

2012 ◽  
Vol 134 (8) ◽  
Author(s):  
Katharine H. Fraser ◽  
Tao Zhang ◽  
M. Ertan Taskin ◽  
Bartley P. Griffith ◽  
Zhongjun J. Wu
Keyword(s):  
Shear Stress ◽  
Platelet Activation ◽  
Exposure Time ◽  
Ventricular Assist Devices ◽  
Shear Stresses ◽  
Residence Times ◽  
Stress Exposure ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Blood Damage

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.

Design Optimization of a Novel Polymeric Prosthetic Heart Valve and a Ventricular Assist Device via Device Thrombogenicity Emulation

2013 ◽  
Author(s):  
Thomas E. Claiborne ◽  
Wei-Che Chiu ◽  
Marvin J. Slepian ◽  
Danny Bluestein
Keyword(s):  
Heart Valves ◽  
Anticoagulation Therapy ◽  
Prosthetic Heart Valve ◽  
Total Artificial Heart ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Prosthetic Heart Valves ◽  
Ventricular Assist ◽  
Mechanical Circulatory Support Devices ◽  
Optimization Methodology

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.

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