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Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing / Gemma Radley

Swansea University Author: Gemma Radley

DOI (Published version): 10.23889/SUthesis.40670

Abstract

Ventricular assist devices (VADs) offer long term therapy to chronic heart failure patients who are ineligible for transplant. However, complications such as infection and thrombosis remain characteristic of VAD therapy.Leukocytes contribute to both infection and thrombosis, but research on the effe...

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Published: Swansea 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa40670
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Abstract: Ventricular assist devices (VADs) offer long term therapy to chronic heart failure patients who are ineligible for transplant. However, complications such as infection and thrombosis remain characteristic of VAD therapy.Leukocytes contribute to both infection and thrombosis, but research on the effect VADs have on these cells is limited. Through observing the impact of biomaterial choice, level of shear stress, and overall VAD design on leukocytes, this research has demonstrated the importance of incorporating leukocyte analysis into VAD testing to better understand and reduce complications.Leukocyte response to VAD-candidate biomaterials (titanium alloy (Ti), diamond-like carbon (DLC), single crystal sapphire (Sap), silicon nitride (SiN), and zirconia toughened alumina (ZTA)) revealed that monocytes become activated in the presence of DLC, Sap and SiN. The addition of shear stress on these biomaterials revealed an immunosuppressive effect by Sap and Ti through attenuated phagocytic function of neutrophils, and an inhibition of cytokine production in response to pathogenic stimuli. This is relevant in that VAD-patients are susceptible to recurrent infections around the driveline.Pro-inflammatory and pro-thrombogenic leukocyte microparticles (LMPs) are produced due to damage or stress. To measure the effect of shear stress on their formation, a mock circulatory loop with the CentriMag™ operated at different conditions was used. The high-speed condition generated the most LMPs that also expressed the activation marker CD11b whereas the standard condition generated the most LMPs expressing HLA-DR. This suggested that operating condition differentially affects leukocyte subsets.To compare the effect of overall VAD design on leukocytes, mock circulatory loops were used to compare the Calon MiniVAD™ with competitor devices. The MiniVAD produced fewer LMPs in comparison to the HVAD™ and HeartMate II™ as well as lower haemolysis and lower platelet activation.This research has shown that material choice, operating condition, and overall VAD design can significantly impact leukocyte activation and functionality. Interestingly, the widely accepted biocompatible material (Ti) utilised in many types of devices, has an immunosuppressive capacity when combined with shear. These findings provide novel insight into why some VAD-patients suffer recurrent infections and sepsis.
Item Description: A selection of third party content is redacted or is partially redacted from this thesis.
Keywords: leukocytes, blood, flow cytometry, VADs
College: Faculty of Medicine, Health and Life Sciences

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