Towards optimization of the thrombogenic potential of blood recirculating cardiovascular devices using modeling approaches

Bluestein, Danny

doi:10.1586/17434440.3.3.267

Cited by 19 publications

(18 citation statements)

References 15 publications

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“…The model of Equation 2 states that platelet activation time course is predicted by a function of the unknown parameter vector P, where (6) is the estimated value of platelet activation at time t i (i = 1,. . .…”

Section: Model Identification Protocolmentioning

confidence: 99%

“…Such an approach should incorporate a model accounting for cellular trauma by means of an activation/damage accumulation hypothesis. 6 Recently, our group has published a comparison of the hemodynamic and thrombogenic performance of two bileaflet mechanical heart valve (MHV) using fluid structure interaction (FSI) modeling that involved the computation of damage accumulation along the trajectories of 15,000 platelets. 7 Correctly implemented, a physically consistent mathematical model for predicting the effects of fluid shear stress on platelets may lead to a better understanding of the phenomenology of thrombosis.…”

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confidence: 99%

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Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to In Vitro Measurements

Nobili

Sheriff²,

Morbiducci³

et al. 2008

ASAIO Journal

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187

218

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The need to optimize the thrombogenic performance of blood recirculating cardiovascular devices, e.g., prosthetic heart valves (PHV) and ventricular assist devices (VAD), is accentuated by the fact that most of them require lifelong anticoagulation therapy that does not eliminate the risk of thromboembolic complications. The formation of thromboemboli in the flow field of these devices is potentiated by contact with foreign surfaces and regional flow phenomena that stimulate blood clotting, especially platelets. With the lack of appropriate methodology, device manufacturers do not specifically optimize for thrombogenic performance. Such optimization can be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. In this study, a phenomenological model for platelet cumulative damage, identified by means of genetic algorithms (GAs), was correlated with in vitro experiments conducted in a Hemodynamic Shearing Device (HSD). Platelets were uniformly exposed to flow shear representing the lower end of the stress levels encountered in devices, and platelet activity state (PAS) was measured in response to six dynamic shear stress waveforms representing repeated passages through a device, and correlated to the predictions of the damage accumulation model. Experimental results demonstrated an increase in PAS with a decrease in "relaxation" time between pulses. The model predictions were in very good agreement with the experimental results.A recognized feature of the complex interplay regulating the pathogenesis of thrombosis is the effect of blood flow-induced mechanical forces on platelets. Physical agonists, such as these flow-induced forces, and chemical agonists, such as adenosine diphosphate and serotonin, trigger platelet activation. This process commences with the secretion of procoagulant and selfstimulating substances from granules, 1 which catalyze thrombin production. 2 As a direct consequence of activation, the platelets undergo a change in shape, marked by pseudopod extension. This increases the strength of adhesion to exogenous surfaces and decreases the resistance to aggregation.One of the major culprits in blood recirculating devices is the emergence of nonphysiologic (pathologic) flow patterns that enhance the hemostatic response. Elevated flow stresses that are present in the nonphysiologic geometries of blood recirculating devices enhance their propensity to initiate thromboembolism. In recent years, it has been demonstrated that flow induced thrombogenicity, caused by chronic platelet activation and the initiation of thrombus formation, is the salient aspect of mechanically induced blood trauma in devices. 3 This lends itself to the hypothesis that thromboembolism in prosthetic blood recirculating devices is

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Section: Model Identification Protocolmentioning

confidence: 99%

mentioning

confidence: 99%

Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to In Vitro Measurements

Nobili

Sheriff²,

Morbiducci³

et al. 2008

ASAIO Journal

Self Cite

187

218

View full text Add to dashboard Cite

show abstract

“…Due to the complexity and the variety of phenomena involved, a universal approach to the problem was (i) incongruous, due to the inherent limitations of mathematical models based only on steady state shear-induced trauma (Grigioni et al, 2004a), and/or (ii) of limited value, due to simplified geometric models/working conditions of the investigated devices (Grigioni et al, 2005a;Dasi et al, 2007). Hence, in the absence of a clear methodology for quantifying the thrombogenic potential of blood re-circulating devices, MHVs are still not necessarily optimized for flow-induced thrombogenicity (Bluestein, 2004(Bluestein, , 2006, and patients receiving even the most up to date designs of MHV still require anticoagulant medication due to the risk of thrombogenic complications and cardioembolic stroke.…”

Section: Introductionmentioning

confidence: 99%

Blood damage safety of prosthetic heart valves. Shear-induced platelet activation and local flow dynamics: A fluid–structure interaction approach

Morbiducci¹,

Ponzini²,

Nobili³

et al. 2009

Journal of Biomechanics

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“…The purpose of the HSD, as discussed in this review, is to be able to replicate shear-stress patterns in and around PHV and other cardiovascular prosthetic devices geometries calculated numerically using novel approaches as discussed previously by the author [117]. Once design optimization has been achieved numerically to minimize the predicted cumulative platelet damage in recirculation devices and PHV [74], the dynamic shear stress information can be fed to the HSD and the effect of such localized stress trajectories on platelet activation can be accurately assessed in vitro.…”

Section: Expert Commentarymentioning

confidence: 99%

Biological effects of dynamic shear stress in cardiovascular pathologies and devices

Girdhar

Bluestein

2008

Expert Review of Medical Devices

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Altered and highly dynamic shear stress conditions have been implicated in endothelial dysfunction leading to cardiovascular disease, and in thromboembolic complications in prosthetic cardiovascular devices. In addition to vascular damage, the pathological flow patterns characterizing cardiovascular pathologies and blood flow in prosthetic devices induce shear activation and damage to blood constituents. Investigation of the specific and accentuated effects of such flow-induced perturbations on individual cell-types in vitro is critical for the optimization of device design, whereby specific design modifications can be made to minimize such perturbations. Such effects are also critical in understanding the development of cardiovascular disease. This review addresses limitations to replicate such dynamic flow conditions in vitro and also introduces the idea of modified in vitro devices, one of which is developed in the authors' laboratory, with dynamic capabilities to investigate the aforementioned effects in greater detail.Keywords cardiovascular disease; cone-plate viscometers; dynamic shear stress; platelet activation; prosthetic heart valves; turbulence Implantable blood recirculation devices, artificial hearts and heart valves, have long been used as life-saving alternatives for people with severe cardiovascular diseases. However, such devices require complex anticoagulation therapy and, as a consequence, are linked to postimplant complications, such as hemorrhage. Despite the anticoagulation therapy, the risk for cardioembolic stroke is not eliminated. Although biocompatibility of these recirculation devices is of utmost importance, optimizing the geometric design of these devices is also critical to avoid flow-induced trauma to blood. Over the years, a definite link between fluid shearstress-induced damage and activation of blood constituents such as platelets and red blood cells, has been established. Irregular flow patterns arising around complex geometries (e.g., the hinge regions of mechanical heart valves [MHV]) have been recently characterized by numerical calculations and noninvasive flow measurements, and are implicated in causing flow-induced thromboembolism (TE). For instance, the Medtronic Parallel™ valve exhibited regions of elevated turbulent stress around the hinges due to its specific geometry, which, in †Author for correspondence: Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, NY 11794-8181, USA, Tel.: +1 631 444 1259, Fax: +1 631 444 6646, danny.bluestein@sunysb.edu. Financial & competing interests disclosure:The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manu...

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Towards optimization of the thrombogenic potential of blood recirculating cardiovascular devices using modeling approaches

Cited by 19 publications

References 15 publications

Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to In Vitro Measurements

Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to In Vitro Measurements

Blood damage safety of prosthetic heart valves. Shear-induced platelet activation and local flow dynamics: A fluid–structure interaction approach

Biological effects of dynamic shear stress in cardiovascular pathologies and devices

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