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Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing / Gemma Radley

Swansea University Author: Gemma Radley

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DOI (Published version): 10.23889/SUthesis.40670

Abstract

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 effe...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa40670
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first_indexed 2018-06-07T13:40:26Z
last_indexed 2020-09-02T03:04:36Z
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2020-09-01T16:07:04.4886335</datestamp><bib-version>v2</bib-version><id>40670</id><entry>2018-06-07</entry><title>Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing</title><swanseaauthors><author><sid>d98559fcf8a6e03bc4c9741ff0af54ba</sid><ORCID>0000-0001-8921-378X</ORCID><firstname>Gemma</firstname><surname>Radley</surname><name>Gemma Radley</name><active>true</active><ethesisStudent>true</ethesisStudent></author></swanseaauthors><date>2018-06-07</date><abstract>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 CentriMag&#x2122; 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 MiniVAD&#x2122; with competitor devices. The MiniVAD produced fewer LMPs in comparison to the HVAD&#x2122; and HeartMate II&#x2122; 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.</abstract><type>E-Thesis</type><journal/><publisher/><keywords>leukocytes, blood, flow cytometry, VADs</keywords><publishedDay>31</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2018</publishedYear><publishedDate>2018-12-31</publishedDate><doi>10.23889/SUthesis.40670</doi><url/><notes>A selection of third party content is redacted or is partially redacted from this thesis.</notes><college>COLLEGE NANME</college><department>Swansea University Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><degreelevel>Doctoral</degreelevel><degreename>Ph.D</degreename><degreesponsorsfunders>Calon Cardio - Technology Ltd</degreesponsorsfunders><apcterm/><lastEdited>2020-09-01T16:07:04.4886335</lastEdited><Created>2018-06-07T12:06:32.5608298</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>Gemma</firstname><surname>Radley</surname><orcid>0000-0001-8921-378X</orcid><order>1</order></author></authors><documents><document><filename>Under embargo</filename><originalFilename>Under embargo</originalFilename><uploaded>2018-07-06T11:28:47.0270000</uploaded><type>Output</type><contentLength>8539328</contentLength><contentType>application/pdf</contentType><version>Redacted version - open access</version><cronfaStatus>true</cronfaStatus><embargoDate>2023-05-10T00:00:00.0000000</embargoDate><documentNotes>A selection of third party content is redacted or is partially redacted from this thesis.</documentNotes><copyrightCorrect>true</copyrightCorrect></document></documents><OutputDurs/></rfc1807>
spelling 2020-09-01T16:07:04.4886335 v2 40670 2018-06-07 Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing d98559fcf8a6e03bc4c9741ff0af54ba 0000-0001-8921-378X Gemma Radley Gemma Radley true true 2018-06-07 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 CentriMag™ 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 MiniVAD™ with competitor devices. The MiniVAD produced fewer LMPs in comparison to the HVAD™ and HeartMate II™ 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. E-Thesis leukocytes, blood, flow cytometry, VADs 31 12 2018 2018-12-31 10.23889/SUthesis.40670 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D Calon Cardio - Technology Ltd 2020-09-01T16:07:04.4886335 2018-06-07T12:06:32.5608298 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Gemma Radley 0000-0001-8921-378X 1 Under embargo Under embargo 2018-07-06T11:28:47.0270000 Output 8539328 application/pdf Redacted version - open access true 2023-05-10T00:00:00.0000000 A selection of third party content is redacted or is partially redacted from this thesis. true
title Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
spellingShingle Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
Gemma Radley
title_short Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
title_full Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
title_fullStr Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
title_full_unstemmed Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
title_sort Impact of ventricular assist devices on the activity of white blood cells and the implications for device design testing
author_id_str_mv d98559fcf8a6e03bc4c9741ff0af54ba
author_id_fullname_str_mv d98559fcf8a6e03bc4c9741ff0af54ba_***_Gemma Radley
author Gemma Radley
author2 Gemma Radley
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/SUthesis.40670
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
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 0
active_str 0
description 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 CentriMag™ 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 MiniVAD™ with competitor devices. The MiniVAD produced fewer LMPs in comparison to the HVAD™ and HeartMate II™ 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.
published_date 2018-12-31T03:51:46Z
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score 11.012924

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