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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 CentriMagTM 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 MiniVADTM with competitor devices. The MiniVAD produced fewer LMPs in comparison to the HVADTM and HeartMate IITM 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. |
