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Shear Stress-Induced Total Blood Trauma in Multiple Species
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The common complications in heart failure patients with implanted ventricular assist devices (VADs) include haemolysis, thrombosis and bleeding, which are linked to shear stress-induced trauma to erythrocytes, platelets and von Willebrand factor (vWF). Novel device designs are being developed to red...
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The common complications in heart failure patients with implanted ventricular assist devices (VADs) include haemolysis, thrombosis and bleeding, which are linked to shear stress-induced trauma to erythrocytes, platelets and von Willebrand factor (vWF). Novel device designs are being developed to reduce the blood trauma, which will need to undergo in vitro and in vivo pre-clinical testing in large animal models such as cattle, sheep and pig. To fully understand the impact of device design and enable translation of pre-clinical results, it is important to identify any potential species-specific differences in the VAD associated common complications. Therefore, the purpose of this study was to evaluate the effects of shear stress on cells and proteins in bovine, ovine, and porcine blood compared to human. Blood from different species was subjected to various shear rates (0 – 8000 s-1) using a rheometer. It was then analysed for complete blood counts, haemolysis by the Harboe assay, platelet activation by flow cytometry, vWF structure by immunoblotting, and function by collagen binding activity ELISA (vWF:CBA). Overall, increasing shear rate caused increased total blood trauma in all tested species. This analysis revealed species-specific differences in shear-induced haemolysis, platelet activation and vWF structure and function. Compared to human blood, porcine blood was the most resilient and showed less haemolysis, similar blood counts, but less platelet activation and less vWF damage in response to shear. Compared to human blood, sheared bovine blood showed less haemolysis, similar blood cell counts, greater platelet activation, and similar degradation of vWF structure, but less impact on its activity in response to shear. The shear-induced effect on ovine blood depended on whether the blood was collected via gravity at the abattoir or by venepuncture from live sheep. Overall, ovine abattoir blood was the least resilient in response to shear and bovine blood was the most similar to human blood. These results lay the foundations for developing blood trauma evaluation standards to enable the extrapolation of in vitro and in vivo animal data to predict safety and biocompatibility of blood-handling medical devices in humans. We discourage the use of ovine abattoir blood and favour the use of bovine blood for in vitro device evaluation but multiple species could be used to create a full understanding of the complication risk profile of new devices. Further, this study highlights that choice of antibody clone for evaluating platelet activation in bovine blood can influence the interpretation of results from different studies.
Shear stress, bovine, human, ovine, porcine, vWF, platelet activation, haemolysis, haematology, rheometry
Faculty of Medicine, Health and Life Sciences