The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction

Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction . MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death. We have shown, both in and models, that ultrasoun...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Theranostics 2017-01, Vol.7 (14), p.3527-3538
Hauptverfasser: Yu, Francois T H, Chen, Xucai, Straub, Adam C, Pacella, John J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 3538
container_issue 14
container_start_page 3527
container_title Theranostics
container_volume 7
creator Yu, Francois T H
Chen, Xucai
Straub, Adam C
Pacella, John J
description Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction . MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death. We have shown, both in and models, that ultrasound and microbubble therapy (termed "sonoreperfusion" or " ") is a theranostic approach that relieves MVO and restores perfusion, but the underlying mechanisms remain to be established. In this study, we investigated the role of nitric oxide ( ) during SRP. We first demonstrated in plated cells that US-stimulated MB oscillations induced a 6-fold increase in endothelial nitric oxide synthase phosphorylation We then monitored the kinetics of intramuscular NO and perfusion flow rate responses following 2-min of SRP therapy in the rat hindlimb muscle, with and without blockade of eNOS with LNAME. Following SRP, we found that starting at 6 minutes, intramuscular NO increased significantly over 30 min and was higher than baseline after 13 min. Concomitant contrast enhanced burst reperfusion imaging confirmed that there was a marked increase in perfusion flow rate at 6 and 10 min post SRP compared to baseline (>2.5 fold). The increases in intramuscular NO and perfusion rate were blunted with LNAME. Finally, we tested the hypothesis that NO plays a role in SRP by assessing reperfusion efficacy in a previously described rat hindlimb model of MVO during blockade of eNOS. After US treatment 1, microvascular blood volume was restored to baseline in the MB+US group, but remained low in the LNAME group. Perfusion rates increased in the MB+US group after US treatment 2 but not in the MB+US+LNAME group. These data strongly support that MB oscillations can activate the eNOS pathway leading to increased blood perfusion and that NO plays a significant role in SRP efficacy.
doi_str_mv 10.7150/thno.19422
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5596441</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1940050921</sourcerecordid><originalsourceid>FETCH-LOGICAL-c444t-abb54a693fe8ab1c793f03e7a52719d08be6b1c7bebc864ca85dc9bb07b448f23</originalsourceid><addsrcrecordid>eNpVkV1LwzAUhoMobszd-AOklyJsJm3aJjeCDL9gOtB5HZL0dIt0zUzaof_e1M0xAyGHnIf3fLwInRM8zkmKr5tlbceE0zg-Qn3CEjbKM4qPD-IeGnr_gcOhOOaEn6JezDgJN-mj6XwJ0autILJl9GIaZ3Q0-zIFREXrTL2I3mxtHazBla03tu6wZ6Od3Uiv20q6aKZ841rdhOQZOill5WG4ewfo_f5uPnkcTWcPT5Pb6UhTSpuRVCqlMuNJCUwqovMQ4QRymcY54QVmCrLuW4HSLKNasrTQXCmcK0pZGScDdLPVXbdqBYWGunGyEmtnVtJ9CyuN-J-pzVIs7EakKc8oJUHgcifg7GcLvhEr4zVUlazBtl6EfWKcYh536NUWDTN776DclyFYdA6IzgHx60CALw4b26N_-05-APRvhA4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1940050921</pqid></control><display><type>article</type><title>The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction</title><source>PubMed Central Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Yu, Francois T H ; Chen, Xucai ; Straub, Adam C ; Pacella, John J</creator><creatorcontrib>Yu, Francois T H ; Chen, Xucai ; Straub, Adam C ; Pacella, John J</creatorcontrib><description>Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction . MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death. We have shown, both in and models, that ultrasound and microbubble therapy (termed "sonoreperfusion" or " ") is a theranostic approach that relieves MVO and restores perfusion, but the underlying mechanisms remain to be established. In this study, we investigated the role of nitric oxide ( ) during SRP. We first demonstrated in plated cells that US-stimulated MB oscillations induced a 6-fold increase in endothelial nitric oxide synthase phosphorylation We then monitored the kinetics of intramuscular NO and perfusion flow rate responses following 2-min of SRP therapy in the rat hindlimb muscle, with and without blockade of eNOS with LNAME. Following SRP, we found that starting at 6 minutes, intramuscular NO increased significantly over 30 min and was higher than baseline after 13 min. Concomitant contrast enhanced burst reperfusion imaging confirmed that there was a marked increase in perfusion flow rate at 6 and 10 min post SRP compared to baseline (&gt;2.5 fold). The increases in intramuscular NO and perfusion rate were blunted with LNAME. Finally, we tested the hypothesis that NO plays a role in SRP by assessing reperfusion efficacy in a previously described rat hindlimb model of MVO during blockade of eNOS. After US treatment 1, microvascular blood volume was restored to baseline in the MB+US group, but remained low in the LNAME group. Perfusion rates increased in the MB+US group after US treatment 2 but not in the MB+US+LNAME group. These data strongly support that MB oscillations can activate the eNOS pathway leading to increased blood perfusion and that NO plays a significant role in SRP efficacy.</description><identifier>ISSN: 1838-7640</identifier><identifier>EISSN: 1838-7640</identifier><identifier>DOI: 10.7150/thno.19422</identifier><identifier>PMID: 28912893</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher</publisher><subject>Research Paper</subject><ispartof>Theranostics, 2017-01, Vol.7 (14), p.3527-3538</ispartof><rights>Ivyspring International Publisher 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-abb54a693fe8ab1c793f03e7a52719d08be6b1c7bebc864ca85dc9bb07b448f23</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596441/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596441/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28912893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Francois T H</creatorcontrib><creatorcontrib>Chen, Xucai</creatorcontrib><creatorcontrib>Straub, Adam C</creatorcontrib><creatorcontrib>Pacella, John J</creatorcontrib><title>The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction . MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death. We have shown, both in and models, that ultrasound and microbubble therapy (termed "sonoreperfusion" or " ") is a theranostic approach that relieves MVO and restores perfusion, but the underlying mechanisms remain to be established. In this study, we investigated the role of nitric oxide ( ) during SRP. We first demonstrated in plated cells that US-stimulated MB oscillations induced a 6-fold increase in endothelial nitric oxide synthase phosphorylation We then monitored the kinetics of intramuscular NO and perfusion flow rate responses following 2-min of SRP therapy in the rat hindlimb muscle, with and without blockade of eNOS with LNAME. Following SRP, we found that starting at 6 minutes, intramuscular NO increased significantly over 30 min and was higher than baseline after 13 min. Concomitant contrast enhanced burst reperfusion imaging confirmed that there was a marked increase in perfusion flow rate at 6 and 10 min post SRP compared to baseline (&gt;2.5 fold). The increases in intramuscular NO and perfusion rate were blunted with LNAME. Finally, we tested the hypothesis that NO plays a role in SRP by assessing reperfusion efficacy in a previously described rat hindlimb model of MVO during blockade of eNOS. After US treatment 1, microvascular blood volume was restored to baseline in the MB+US group, but remained low in the LNAME group. Perfusion rates increased in the MB+US group after US treatment 2 but not in the MB+US+LNAME group. These data strongly support that MB oscillations can activate the eNOS pathway leading to increased blood perfusion and that NO plays a significant role in SRP efficacy.</description><subject>Research Paper</subject><issn>1838-7640</issn><issn>1838-7640</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpVkV1LwzAUhoMobszd-AOklyJsJm3aJjeCDL9gOtB5HZL0dIt0zUzaof_e1M0xAyGHnIf3fLwInRM8zkmKr5tlbceE0zg-Qn3CEjbKM4qPD-IeGnr_gcOhOOaEn6JezDgJN-mj6XwJ0autILJl9GIaZ3Q0-zIFREXrTL2I3mxtHazBla03tu6wZ6Od3Uiv20q6aKZ841rdhOQZOill5WG4ewfo_f5uPnkcTWcPT5Pb6UhTSpuRVCqlMuNJCUwqovMQ4QRymcY54QVmCrLuW4HSLKNasrTQXCmcK0pZGScDdLPVXbdqBYWGunGyEmtnVtJ9CyuN-J-pzVIs7EakKc8oJUHgcifg7GcLvhEr4zVUlazBtl6EfWKcYh536NUWDTN776DclyFYdA6IzgHx60CALw4b26N_-05-APRvhA4</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Yu, Francois T H</creator><creator>Chen, Xucai</creator><creator>Straub, Adam C</creator><creator>Pacella, John J</creator><general>Ivyspring International Publisher</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170101</creationdate><title>The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction</title><author>Yu, Francois T H ; Chen, Xucai ; Straub, Adam C ; Pacella, John J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-abb54a693fe8ab1c793f03e7a52719d08be6b1c7bebc864ca85dc9bb07b448f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Research Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Francois T H</creatorcontrib><creatorcontrib>Chen, Xucai</creatorcontrib><creatorcontrib>Straub, Adam C</creatorcontrib><creatorcontrib>Pacella, John J</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Theranostics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Francois T H</au><au>Chen, Xucai</au><au>Straub, Adam C</au><au>Pacella, John J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction</atitle><jtitle>Theranostics</jtitle><addtitle>Theranostics</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>7</volume><issue>14</issue><spage>3527</spage><epage>3538</epage><pages>3527-3538</pages><issn>1838-7640</issn><eissn>1838-7640</eissn><abstract>Microembolization during PCI for acute myocardial infarction can cause microvascular obstruction . MVO severely limits the success of reperfusion therapies, is associated with additional myonecrosis, and is linked to worse prognosis, including death. We have shown, both in and models, that ultrasound and microbubble therapy (termed "sonoreperfusion" or " ") is a theranostic approach that relieves MVO and restores perfusion, but the underlying mechanisms remain to be established. In this study, we investigated the role of nitric oxide ( ) during SRP. We first demonstrated in plated cells that US-stimulated MB oscillations induced a 6-fold increase in endothelial nitric oxide synthase phosphorylation We then monitored the kinetics of intramuscular NO and perfusion flow rate responses following 2-min of SRP therapy in the rat hindlimb muscle, with and without blockade of eNOS with LNAME. Following SRP, we found that starting at 6 minutes, intramuscular NO increased significantly over 30 min and was higher than baseline after 13 min. Concomitant contrast enhanced burst reperfusion imaging confirmed that there was a marked increase in perfusion flow rate at 6 and 10 min post SRP compared to baseline (&gt;2.5 fold). The increases in intramuscular NO and perfusion rate were blunted with LNAME. Finally, we tested the hypothesis that NO plays a role in SRP by assessing reperfusion efficacy in a previously described rat hindlimb model of MVO during blockade of eNOS. After US treatment 1, microvascular blood volume was restored to baseline in the MB+US group, but remained low in the LNAME group. Perfusion rates increased in the MB+US group after US treatment 2 but not in the MB+US+LNAME group. These data strongly support that MB oscillations can activate the eNOS pathway leading to increased blood perfusion and that NO plays a significant role in SRP efficacy.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher</pub><pmid>28912893</pmid><doi>10.7150/thno.19422</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1838-7640
ispartof Theranostics, 2017-01, Vol.7 (14), p.3527-3538
issn 1838-7640
1838-7640
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5596441
source PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Research Paper
title The Role of Nitric Oxide during Sonoreperfusion of Microvascular Obstruction
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T23%3A07%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Role%20of%20Nitric%20Oxide%20during%20Sonoreperfusion%20of%20Microvascular%20Obstruction&rft.jtitle=Theranostics&rft.au=Yu,%20Francois%20T%20H&rft.date=2017-01-01&rft.volume=7&rft.issue=14&rft.spage=3527&rft.epage=3538&rft.pages=3527-3538&rft.issn=1838-7640&rft.eissn=1838-7640&rft_id=info:doi/10.7150/thno.19422&rft_dat=%3Cproquest_pubme%3E1940050921%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1940050921&rft_id=info:pmid/28912893&rfr_iscdi=true