Journal article 1211 views 483 downloads
Shear Stress-Induced Total Blood Trauma in Multiple Species
Chris H. H. Chan,
Ina Laura Pieper,
Christian R. Robinson,
Yasmin Friedmann,
Venkat Kanamarlapudi ,
Cathy Thornton
Artificial Organs
Swansea University Authors: Yasmin Friedmann, Venkat Kanamarlapudi , Cathy Thornton
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DOI (Published version): 10.1111/aor.12932
Abstract
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...
Published in: | Artificial Organs |
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ISSN: | 0160564X |
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2017
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URI: | https://cronfa.swan.ac.uk/Record/cronfa31746 |
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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. 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2021-11-19T04:00:07.1345934 v2 31746 2017-01-25 Shear Stress-Induced Total Blood Trauma in Multiple Species 94dd4462b95e78880040791727786dfc Yasmin Friedmann Yasmin Friedmann true false 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false c71a7a4be7361094d046d312202bce0c 0000-0002-5153-573X Cathy Thornton Cathy Thornton true false 2017-01-25 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. Journal Article Artificial Organs 0160564X Shear stress, bovine, human, ovine, porcine, vWF, platelet activation, haemolysis, haematology, rheometry 26 7 2017 2017-07-26 10.1111/aor.12932 COLLEGE NANME COLLEGE CODE Swansea University 2021-11-19T04:00:07.1345934 2017-01-25T13:56:02.0607637 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Chris H. H. Chan 1 Ina Laura Pieper 2 Christian R. Robinson 3 Yasmin Friedmann 4 Venkat Kanamarlapudi 0000-0002-8739-1483 5 Cathy Thornton 0000-0002-5153-573X 6 0031746-27072017104523.pdf MultispeciesMaintextfileRISSUv2.pdf 2017-07-27T10:45:23.3670000 Output 688998 application/pdf Accepted Manuscript true 2018-07-27T00:00:00.0000000 true eng |
title |
Shear Stress-Induced Total Blood Trauma in Multiple Species |
spellingShingle |
Shear Stress-Induced Total Blood Trauma in Multiple Species Yasmin Friedmann Venkat Kanamarlapudi Cathy Thornton |
title_short |
Shear Stress-Induced Total Blood Trauma in Multiple Species |
title_full |
Shear Stress-Induced Total Blood Trauma in Multiple Species |
title_fullStr |
Shear Stress-Induced Total Blood Trauma in Multiple Species |
title_full_unstemmed |
Shear Stress-Induced Total Blood Trauma in Multiple Species |
title_sort |
Shear Stress-Induced Total Blood Trauma in Multiple Species |
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author |
Yasmin Friedmann Venkat Kanamarlapudi Cathy Thornton |
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Chris H. H. Chan Ina Laura Pieper Christian R. Robinson Yasmin Friedmann Venkat Kanamarlapudi Cathy Thornton |
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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. |
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2017-07-26T04:04:34Z |
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