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Shear Stress-Induced Total Blood Trauma in Multiple Species / Chris H. H. Chan; Ina Laura Pieper; Christian R. Robinson; Yasmin Friedmann; Venkateswarlu Kanamarlapudi; Catherine A. Thornton
Swansea University Author: Kanamarlapudi, Venkat
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The common complications in heart failurepatients with implanted ventricular assist devices (VADs)include hemolysis, thrombosis, and bleeding. These are linkedto shear stress-induced trauma to erythrocytes, platelets, andvon Willebrand factor (vWF). Novel device designs are beingdeveloped to reduce...
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The common complications in heart failurepatients with implanted ventricular assist devices (VADs)include hemolysis, thrombosis, and bleeding. These are linkedto shear stress-induced trauma to erythrocytes, platelets, andvon Willebrand factor (vWF). Novel device designs are beingdeveloped to reduce the blood trauma, which will need toundergo in vitro and in vivo preclinical testing in large animalmodels such as cattle, sheep, and pig. To fully understand theimpact of device design and enable translation of preclinicalresults, it is important to identify any potential species-specificdifferences in the VAD-associated common complications.Therefore, the purpose of this study was to evaluate the effectsof shear stress on cells and proteins in bovine, ovine, and porcineblood compared to human. Blood from different specieswas subjected to various shear rates (0–8000/s) using a rheometer.It was then analyzed for complete blood counts, hemolysisby the Harboe assay, platelet activation by flow cytometry,vWF structure by immunoblotting, and function by collagenbinding activity ELISA (vWF : CBA). Overall, increasingshear rate caused increased total blood trauma in all testedspecies. This analysis revealed species-specific differences inshear-induced hemolysis, platelet activation, and vWF structureand function. Compared to human blood, porcine bloodwas the most resilient and showed less hemolysis, similarblood counts, but less platelet activation and less vWF damagein response to shear. Compared to human blood, shearedbovine blood showed less hemolysis, similar blood cell counts,greater platelet activation, and similar degradation of vWFstructure, but less impact on its activity in response to shear.The shear-induced effect on ovine blood depended on whetherthe blood was collected via gravity at the abattoir or by venepuncturefrom live sheep. Overall, ovine abattoir blood wasthe least resilient in response to shear and bovine blood wasthe most similar to human blood. These results lay the foundationsfor developing blood trauma evaluation standards toenable the extrapolation of in vitro and in vivo animal data topredict safety and biocompatibility of blood-handling medicaldevices in humans. We advise using ovine venepuncture bloodinstead of ovine abattoir blood due to the greater overall damagein the latter. We propose using bovine blood for totalblood damage in vitro device evaluation but multiple speciescould be used to create a full understanding of the complicationrisk profile of new devices. Further, this study highlightsthat choice of antibody clone for evaluating platelet activationin bovine blood can influence the interpretation of resultsfrom different studies.
Shear stress, Bovine, Human, Ovine, Porcine, von Willebrand factor, Platelet activation, Hemolysis, Hematology, Rheometry.
Swansea University Medical School