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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, Venkat Kanamarlapudi Orcid Logo, Cathy Thornton Orcid Logo

Artificial Organs

Swansea University Authors: Yasmin Friedmann, Venkat Kanamarlapudi Orcid Logo, Cathy Thornton Orcid Logo

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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...

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Published in: Artificial Organs
ISSN: 0160564X
Published: 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 &#x2013; 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.</abstract><type>Journal Article</type><journal>Artificial Organs</journal><volume/><journalNumber/><paginationStart/><paginationEnd/><publisher/><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0160564X</issnPrint><issnElectronic/><keywords>Shear stress, bovine, human, ovine, porcine, vWF, platelet activation, haemolysis, haematology, rheometry</keywords><publishedDay>26</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2017</publishedYear><publishedDate>2017-07-26</publishedDate><doi>10.1111/aor.12932</doi><url/><notes/><college>COLLEGE NANME</college><department>Medicine</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>PMSC</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2021-11-19T04:00:07.1345934</lastEdited><Created>2017-01-25T13:56:02.0607637</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Chris H. H.</firstname><surname>Chan</surname><order>1</order></author><author><firstname>Ina Laura</firstname><surname>Pieper</surname><order>2</order></author><author><firstname>Christian R.</firstname><surname>Robinson</surname><order>3</order></author><author><firstname>Yasmin</firstname><surname>Friedmann</surname><order>4</order></author><author><firstname>Venkat</firstname><surname>Kanamarlapudi</surname><orcid>0000-0002-8739-1483</orcid><order>5</order></author><author><firstname>Cathy</firstname><surname>Thornton</surname><orcid>0000-0002-5153-573X</orcid><order>6</order></author></authors><documents><document><filename>0031746-27072017104523.pdf</filename><originalFilename>MultispeciesMaintextfileRISSUv2.pdf</originalFilename><uploaded>2017-07-27T10:45:23.3670000</uploaded><type>Output</type><contentLength>688998</contentLength><contentType>application/pdf</contentType><version>Accepted Manuscript</version><cronfaStatus>true</cronfaStatus><embargoDate>2018-07-27T00:00:00.0000000</embargoDate><copyrightCorrect>true</copyrightCorrect><language>eng</language></document></documents><OutputDurs/></rfc1807>
spelling 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 PMSC 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 Medicine COLLEGE CODE PMSC 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
author_id_str_mv 94dd4462b95e78880040791727786dfc
63741801137148abfa4c00cd547dcdfa
c71a7a4be7361094d046d312202bce0c
author_id_fullname_str_mv 94dd4462b95e78880040791727786dfc_***_Yasmin Friedmann
63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
c71a7a4be7361094d046d312202bce0c_***_Cathy Thornton
author Yasmin Friedmann
Venkat Kanamarlapudi
Cathy Thornton
author2 Chris H. H. Chan
Ina Laura Pieper
Christian R. Robinson
Yasmin Friedmann
Venkat Kanamarlapudi
Cathy Thornton
format Journal article
container_title Artificial Organs
publishDate 2017
institution Swansea University
issn 0160564X
doi_str_mv 10.1111/aor.12932
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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.
published_date 2017-07-26T03:38:47Z
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