Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model
[Display omitted] Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial...
Gespeichert in:
| Veröffentlicht in: | The Journal of heart and lung transplantation 2019-04, Vol.38 (4), p.456-465 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 465 |
|---|---|
| container_issue | 4 |
| container_start_page | 456 |
| container_title | The Journal of heart and lung transplantation |
| container_volume | 38 |
| creator | Haglund, Thomas A. Rajasekaran, Namakkal S. Smood, Benjamin Giridharan, Guruprasad A. Hoopes, Charles W. Holman, William L. Mauchley, David C. Prabhu, Sumanth D. Pamboukian, Salpy V. Tallaj, Jose A. Rajapreyar, Indranee N. Kirklin, James K. Sethu, Palaniappan |
| description | [Display omitted]
Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated.
The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2–related factor 2 (Nrf-2)–regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility.
Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2–activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2–regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN.
HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation. |
| doi_str_mv | 10.1016/j.healun.2018.10.007 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2149031432</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1053249818317303</els_id><sourcerecordid>2149031432</sourcerecordid><originalsourceid>FETCH-LOGICAL-c362t-20b29529a6d98daf1aa41ed440bd58cf9f1fb53f6873a92d614e02a6f22a78b93</originalsourceid><addsrcrecordid>eNp9kMtuHCEQRZGVyHZs_0EUsfSmJ7z6tYlkWWMnkqVsnDWiocgwYmACdFv-ezNqJ8tsAN26dYs6CH2mZEMJ7b7uNztQfg4bRuhQpQ0h_Rm6pG3bN5zS_kN9k5Y3TIzDBfqU854QwnjLztEFJy3hpBeX6GW71BBVXAw4Wmx9fGkO0cx-ldTxmKLSO8jYBbxAKMnpWkxY5exywQYWp2t1zi78xipUW7O4kiKGYGLZgXfKYw2-HrMvcwJc48Ffo49W-Qw37_cV-vWwfb7_3jz9fPxxf_fUaN6x0jAysbFlo-rMOBhlqVKCghGCTKYdtB0ttVPLbTf0XI3MdFQAYaqzjKl-mEZ-hW7X3LrHnxlykQeXT99RAeKcJaNiJJwKzqpVrFadYs4JrDwmd1DpVVIiT8jlXq7I5Qn5Sa3Ia9uX9wnzdADzr-kv42r4thqg7rk4SDJrB0GDcQl0kSa6_094A8xalrs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2149031432</pqid></control><display><type>article</type><title>Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model</title><source>Elsevier ScienceDirect Journals Complete</source><creator>Haglund, Thomas A. ; Rajasekaran, Namakkal S. ; Smood, Benjamin ; Giridharan, Guruprasad A. ; Hoopes, Charles W. ; Holman, William L. ; Mauchley, David C. ; Prabhu, Sumanth D. ; Pamboukian, Salpy V. ; Tallaj, Jose A. ; Rajapreyar, Indranee N. ; Kirklin, James K. ; Sethu, Palaniappan</creator><creatorcontrib>Haglund, Thomas A. ; Rajasekaran, Namakkal S. ; Smood, Benjamin ; Giridharan, Guruprasad A. ; Hoopes, Charles W. ; Holman, William L. ; Mauchley, David C. ; Prabhu, Sumanth D. ; Pamboukian, Salpy V. ; Tallaj, Jose A. ; Rajapreyar, Indranee N. ; Kirklin, James K. ; Sethu, Palaniappan</creatorcontrib><description>[Display omitted]
Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated.
The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2–related factor 2 (Nrf-2)–regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility.
Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2–activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2–regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN.
HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation.</description><identifier>ISSN: 1053-2498</identifier><identifier>EISSN: 1557-3117</identifier><identifier>DOI: 10.1016/j.healun.2018.10.007</identifier><identifier>PMID: 30503074</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>continuous-flow ventricular assist device ; diminished pulsatility ; endothelial cell culture model ; endothelial dysfunction ; flow modulation</subject><ispartof>The Journal of heart and lung transplantation, 2019-04, Vol.38 (4), p.456-465</ispartof><rights>2018 International Society for Heart and Lung Transplantation</rights><rights>Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-20b29529a6d98daf1aa41ed440bd58cf9f1fb53f6873a92d614e02a6f22a78b93</citedby><cites>FETCH-LOGICAL-c362t-20b29529a6d98daf1aa41ed440bd58cf9f1fb53f6873a92d614e02a6f22a78b93</cites><orcidid>0000-0001-7658-555X ; 0000-0002-8667-6591 ; 0000-0002-5794-2037</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.healun.2018.10.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30503074$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haglund, Thomas A.</creatorcontrib><creatorcontrib>Rajasekaran, Namakkal S.</creatorcontrib><creatorcontrib>Smood, Benjamin</creatorcontrib><creatorcontrib>Giridharan, Guruprasad A.</creatorcontrib><creatorcontrib>Hoopes, Charles W.</creatorcontrib><creatorcontrib>Holman, William L.</creatorcontrib><creatorcontrib>Mauchley, David C.</creatorcontrib><creatorcontrib>Prabhu, Sumanth D.</creatorcontrib><creatorcontrib>Pamboukian, Salpy V.</creatorcontrib><creatorcontrib>Tallaj, Jose A.</creatorcontrib><creatorcontrib>Rajapreyar, Indranee N.</creatorcontrib><creatorcontrib>Kirklin, James K.</creatorcontrib><creatorcontrib>Sethu, Palaniappan</creatorcontrib><title>Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model</title><title>The Journal of heart and lung transplantation</title><addtitle>J Heart Lung Transplant</addtitle><description>[Display omitted]
Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated.
The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2–related factor 2 (Nrf-2)–regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility.
Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2–activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2–regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN.
HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation.</description><subject>continuous-flow ventricular assist device</subject><subject>diminished pulsatility</subject><subject>endothelial cell culture model</subject><subject>endothelial dysfunction</subject><subject>flow modulation</subject><issn>1053-2498</issn><issn>1557-3117</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kMtuHCEQRZGVyHZs_0EUsfSmJ7z6tYlkWWMnkqVsnDWiocgwYmACdFv-ezNqJ8tsAN26dYs6CH2mZEMJ7b7uNztQfg4bRuhQpQ0h_Rm6pG3bN5zS_kN9k5Y3TIzDBfqU854QwnjLztEFJy3hpBeX6GW71BBVXAw4Wmx9fGkO0cx-ldTxmKLSO8jYBbxAKMnpWkxY5exywQYWp2t1zi78xipUW7O4kiKGYGLZgXfKYw2-HrMvcwJc48Ffo49W-Qw37_cV-vWwfb7_3jz9fPxxf_fUaN6x0jAysbFlo-rMOBhlqVKCghGCTKYdtB0ttVPLbTf0XI3MdFQAYaqzjKl-mEZ-hW7X3LrHnxlykQeXT99RAeKcJaNiJJwKzqpVrFadYs4JrDwmd1DpVVIiT8jlXq7I5Qn5Sa3Ia9uX9wnzdADzr-kv42r4thqg7rk4SDJrB0GDcQl0kSa6_094A8xalrs</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Haglund, Thomas A.</creator><creator>Rajasekaran, Namakkal S.</creator><creator>Smood, Benjamin</creator><creator>Giridharan, Guruprasad A.</creator><creator>Hoopes, Charles W.</creator><creator>Holman, William L.</creator><creator>Mauchley, David C.</creator><creator>Prabhu, Sumanth D.</creator><creator>Pamboukian, Salpy V.</creator><creator>Tallaj, Jose A.</creator><creator>Rajapreyar, Indranee N.</creator><creator>Kirklin, James K.</creator><creator>Sethu, Palaniappan</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7658-555X</orcidid><orcidid>https://orcid.org/0000-0002-8667-6591</orcidid><orcidid>https://orcid.org/0000-0002-5794-2037</orcidid></search><sort><creationdate>201904</creationdate><title>Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model</title><author>Haglund, Thomas A. ; Rajasekaran, Namakkal S. ; Smood, Benjamin ; Giridharan, Guruprasad A. ; Hoopes, Charles W. ; Holman, William L. ; Mauchley, David C. ; Prabhu, Sumanth D. ; Pamboukian, Salpy V. ; Tallaj, Jose A. ; Rajapreyar, Indranee N. ; Kirklin, James K. ; Sethu, Palaniappan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-20b29529a6d98daf1aa41ed440bd58cf9f1fb53f6873a92d614e02a6f22a78b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>continuous-flow ventricular assist device</topic><topic>diminished pulsatility</topic><topic>endothelial cell culture model</topic><topic>endothelial dysfunction</topic><topic>flow modulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haglund, Thomas A.</creatorcontrib><creatorcontrib>Rajasekaran, Namakkal S.</creatorcontrib><creatorcontrib>Smood, Benjamin</creatorcontrib><creatorcontrib>Giridharan, Guruprasad A.</creatorcontrib><creatorcontrib>Hoopes, Charles W.</creatorcontrib><creatorcontrib>Holman, William L.</creatorcontrib><creatorcontrib>Mauchley, David C.</creatorcontrib><creatorcontrib>Prabhu, Sumanth D.</creatorcontrib><creatorcontrib>Pamboukian, Salpy V.</creatorcontrib><creatorcontrib>Tallaj, Jose A.</creatorcontrib><creatorcontrib>Rajapreyar, Indranee N.</creatorcontrib><creatorcontrib>Kirklin, James K.</creatorcontrib><creatorcontrib>Sethu, Palaniappan</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of heart and lung transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haglund, Thomas A.</au><au>Rajasekaran, Namakkal S.</au><au>Smood, Benjamin</au><au>Giridharan, Guruprasad A.</au><au>Hoopes, Charles W.</au><au>Holman, William L.</au><au>Mauchley, David C.</au><au>Prabhu, Sumanth D.</au><au>Pamboukian, Salpy V.</au><au>Tallaj, Jose A.</au><au>Rajapreyar, Indranee N.</au><au>Kirklin, James K.</au><au>Sethu, Palaniappan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model</atitle><jtitle>The Journal of heart and lung transplantation</jtitle><addtitle>J Heart Lung Transplant</addtitle><date>2019-04</date><risdate>2019</risdate><volume>38</volume><issue>4</issue><spage>456</spage><epage>465</epage><pages>456-465</pages><issn>1053-2498</issn><eissn>1557-3117</eissn><abstract>[Display omitted]
Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated.
The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2–related factor 2 (Nrf-2)–regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility.
Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2–activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2–regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN.
HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30503074</pmid><doi>10.1016/j.healun.2018.10.007</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7658-555X</orcidid><orcidid>https://orcid.org/0000-0002-8667-6591</orcidid><orcidid>https://orcid.org/0000-0002-5794-2037</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1053-2498 |
| ispartof | The Journal of heart and lung transplantation, 2019-04, Vol.38 (4), p.456-465 |
| issn | 1053-2498 1557-3117 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2149031432 |
| source | Elsevier ScienceDirect Journals Complete |
| subjects | continuous-flow ventricular assist device diminished pulsatility endothelial cell culture model endothelial dysfunction flow modulation |
| title | Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T13%3A31%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20flow-modulation%20approaches%20in%20ventricular%20assist%20devices%20using%20an%20in-vitro%20endothelial%20cell%20culture%20model&rft.jtitle=The%20Journal%20of%20heart%20and%20lung%20transplantation&rft.au=Haglund,%20Thomas%20A.&rft.date=2019-04&rft.volume=38&rft.issue=4&rft.spage=456&rft.epage=465&rft.pages=456-465&rft.issn=1053-2498&rft.eissn=1557-3117&rft_id=info:doi/10.1016/j.healun.2018.10.007&rft_dat=%3Cproquest_cross%3E2149031432%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2149031432&rft_id=info:pmid/30503074&rft_els_id=S1053249818317303&rfr_iscdi=true |