Biological effects of dynamic shear stress in cardiovascular pathologies and devices

Abstract

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...

Significance of Extensional Stresses to Red Blood Cell Lysis in a Shearing Flow

“…These shortcomings are important because they compromise the validity of catastrophic damage estimates made by engineers working on the design, development and improvement of life-saving medical devices. 17,47 Interest in mechanical trauma remains high as evidenced by a recent FDA Critical Path Initiative. In 2009, a total of 28 groups across the country performed numerical simulations to predict stress levels and hemolysis in a model flow with features known to cause hemolysis, particularly turbulent blood flow through a sudden contraction or sudden expansion.…”

von Willebrand factor self-association on platelet GpIbα under hydrodynamic shear: effect on shear-induced platelet activation

“…on March 28, 2019. by guest www.bloodjournal.org From prosthetic cardiovascular devices. 15,16 Thus, in addition to regulating VWF-GpIb␣ binding affinity, fluid shear driven VWF selfassociation may also alter the avidity of this molecular interaction. Using a model of shear-induced platelet activation (SIPAct), 13 we show that the self-associated VWF formed on the mechanosensitive receptor GpIb␣ is functional.…”

On the Use of the Platelet Activity State Assay for the In Vitro Quantification of Platelet Activation in Blood Recirculating Devices for Extracorporeal Circulation

“…It has been used as the final step of an advanced design methodology, known as device thrombogenicity emulation (DTE) (18)(19)(20). This approach couples in silico analysis, to extract device-specific flow conditions in the numerical virtual domain, with in vitro experiments; specifically, selected most critical shear stress patterns are replicated on platelet samples through an experimental apparatus, named hemodynamic shearing device (19), emulating the predicted flow conditions; finally, the related thrombogenic potential is quantified through the PAS assay. The DTE is a straightforward process to optimize the thrombogenic performance of devices by estimating the effects of modifications of specific design parameters in terms of devicerelated hemodynamics.…”