Effect of RVAD Cannulation Length on Right Ventricular Thrombosis Risk: An In Silico Investigation.

Left ventricular assist devices (LVADs) have been used off-label as long-term support of the right heart due to the lack of a clinically approved durable right VAD (RVAD). Whilst various techniques to reduce RVAD inflow cannula protrusion have been described, the implication of the protrusion length on right heart blood flow and subsequent risk of thrombosis remains poorly understood. This study investigates the influence of RVAD diaphragmatic cannulation length on right ventricular thrombosis risk using a patient-specific right ventricle in silico model validated with particle image velocimetry.

Current and future strategies to monitor and manage coagulation in ECMO patients.

Extracorporeal membrane oxygenation (ECMO) can provide life-saving support for critically ill patients suffering severe respiratory and/or cardiac failure. However, thrombosis and bleeding remain common and complex problems to manage. Key causes of thrombosis in ECMO patients include blood contact to pro-thrombotic and non-physiological surfaces, as well as high shearing forces in the pump and membrane oxygenator.

In silico Prediction of Thrombosis Risk in a Ventricular Assist Device Supported Right Heart: The Impact of Cannulation Site.

Right ventricular assist device (RVAD) associated thrombosis is a serious complication that may arise due to unfavorable blood flow dynamics (blood stasis) caused by RVAD cannula protrusion within the chambers. This study aims to investigate the thrombosis risk of cannulation via the right atrium (RA) and right ventricle (RV) (diaphragmatic) under full RVAD support using computational fluid dynamics. A HeartWare HVAD inflow cannula was virtually implanted in either the RA or RV of a rigid-walled right heart geometry (including RA, RV, superior, and inferior vena cava) extracted from computed tomography data of a biventricular support patient.

Improved Drainage Cannula Design to Reduce Thrombosis in Veno-Arterial Extracorporeal Membrane Oxygenation.

Thrombosis is a potentially life-threatening complication in veno-arterial extracorporeal membrane oxygenation (ECMO) circuits, which may originate from the drainage cannula due to unfavorable blood flow dynamics. This study aims to numerically investigate the effect of cannula design parameters on local fluid dynamics, and thus thrombosis potential, within ECMO drainage cannulas. A control cannula based on the geometry of a 17 Fr Medtronic drainage cannula concentrically placed in an idealized, rigid-walled geometry of the right atrium and superior and inferior vena cava was numerically modeled.

Novel Stenotic Microchannels to Study Thrombus Formation in Shear Gradients: Influence of Shear Forces and Human Platelet-Related Factors.

Thrombus formation in hemostasis or thrombotic disease is initiated by the rapid adhesion, activation, and aggregation of circulating platelets in flowing blood. At arterial or pathological shear rates, for example due to vascular stenosis or circulatory support devices, platelets may be exposed to highly pulsatile blood flow, while even under constant flow platelets are exposed to pulsation due to thrombus growth or changes in vessel geometry. The aim of this study is to investigate platelet thrombus formation dynamics within flow conditions consisting of either constant or variable shear.

A-Disintegrin-And-Metalloproteinase (ADAM) 10 Activity on Resting and Activated Platelets.

The primary platelet collagen receptor, glycoprotein VI (GPVI), plays an important role in platelet activation and thrombosis. The ectodomain of human GPVI (sGPVI) is proteolytically shed from human platelets by a-disintegrin-and-metalloproteinase 10 (ADAM10). In this study, we used a novel ADAM10-sensitive fluorescence resonance energy transfer sensor to analyze ADAM10-mediated shedding of GPVI from human platelets in response to the exposure of GPVI ligands collagen-related peptide (10 μg/mL), collagen (10 μg/mL), and convulxin (0.

Methods to Determine the Lagrangian Shear Experienced by Platelets during Thrombus Growth.

Platelets can become activated in response to changes in flow-induced shear; however, the underlying molecular mechanisms are not clearly understood. Here we present new techniques for experimentally measuring the flow-induced shear rate experienced by platelets prior to adhering to a thrombus. We examined the dynamics of blood flow around experimentally grown thrombus geometries using a novel combination of experimental (ex vivo) and numerical (in silico) methodologies.

Functional imaging to understand biomechanics: a critical tool for the study of biology, pathology and the development of pharmacological solutions.

We present four case studies of the literature discussing the effects of physical forces on biological function. While the field of biomechanics has existed for many decades, it may be considered by some a poor cousin to biochemistry and other traditional fields of medical research. In these case studies, including cardiovascular and respiratory systems, we demonstrate that, in fact, many systems historically believed to be controlled by biochemistry are dominated by biomechanics.

Effect of hemodynamic forces on platelet aggregation geometry.

The shear rate dependence of platelet aggregation geometries is investigated using a combination of in vitro and numerical experiments. Changes in upstream shear rate, γ(Pw), are found to cause systematic changes in mature platelet aggregation geometries. However, γ(Pw) is not the only factor determining the shear rate experienced by a platelet moving over, and adhering to, a platelet aggregation: flow simulations demonstrate that naturally occurring variations in platelet aggregation geometry cause the local shear rate on the surface of a mature platelet aggregation to vary between zero and up to eight times γ(Pw).

A shear gradient-dependent platelet aggregation mechanism drives thrombus formation.

Platelet aggregation at sites of vascular injury is essential for hemostasis and arterial thrombosis. It has long been assumed that platelet aggregation and thrombus growth are initiated by soluble agonists generated at sites of vascular injury. By using high-resolution intravital imaging techniques and hydrodynamic analyses, we show that platelet aggregation is primarily driven by changes in blood flow parameters (rheology), with soluble agonists having a secondary role, stabilizing formed aggregates.

Modified control grid interpolation for the volumetric reconstruction of fluid flows.

Complex applications in fluid dynamics research often require more highly resolved velocity data than direct measurements or simulations provide. The advent of stereo PIV and PCMR techniques has advanced the state-of-the-art in flow velocity measurement, but 3D spatial resolution remains limited. Here a new technique is proposed for velocity data interpolation to address this problem.

Fluid dynamic assessment of three polymeric heart valves using particle image velocimetry.

Polymeric heart valves have the potential to reduce thrombogenic complications associated with current mechanical valves and overcome fatigue-related problems experienced by bioprosthetic valves. In this paper we characterize the in vitro velocity and Reynolds Shear Stress (RSS) fields inside and downstream of three different prototype trileaflet polymeric heart valves. The fluid dynamic differences are then correlated with variations in valve design parameters.

A comparison of flow field structures of two tri-leaflet polymeric heart valves.

Polymeric heart valves have the potential to reduce thrombogenic complications associated with current mechanical valves and overcome fatigue-related problems experienced by bioprosthetic valves. In this in vitro study, the velocity fields inside and downstream of two different prototype tri-lealfet polymeric heart valves were studied. Experiments were conducted on two 23 mm prototype polymeric valves, provided by AorTech Europe, having open or closed commissure designs and leaflet thickness of 120 and 80 microm, respectively.

Comparison of the hinge flow fields of two bileaflet mechanical heart valves under aortic and mitral conditions.

Background: Animal and clinical studies have shown that bileaflet mechanical heart valve designs are plagued by thromboembolic complications, with higher rates in the mitral than in the aortic position. This study evaluated the hinge flow dynamic of the 23 mm St. Jude Medical (SJM) Regent and the 23 mm CarboMedics (CM) valves under aortic conditions and compared these results with previous findings under mitral conditions.