Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia
(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic...
Gespeichert in:
Veröffentlicht in: | Journal of clinical medicine 2022-06, Vol.11 (12), p.3343 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | 12 |
container_start_page | 3343 |
container_title | Journal of clinical medicine |
container_volume | 11 |
creator | Gelhard, Sarah Kestner, Roxane-Isabelle Armbrust, Moritz Steinmetz, Helmuth Foerch, Christian Bohmann, Ferdinand O. |
description | (1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role. |
doi_str_mv | 10.3390/jcm11123343 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9225099</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2681042610</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-83b6daa0c97e8477b97066dbdfca5bde2bd328281740bca490b883d4c97acccb3</originalsourceid><addsrcrecordid>eNpdkt9qFDEUhwdRbGl75QsEvBFkbf7tJOOFIGvtFqpCXa9DksnsZJtJ1pOZ1n0zH69pu0hrbk7C7zsfJ3Cq6g3BHxhr8OnGDoQQyhhnL6pDioWYYSbZyyf3g-ok5w0uR0pOiXhdHbC54IzT-WH19-zPNiTwcY0WKY6gfWy91aNPMaMuAVr1kAaTwi77_BFd-XyNUoeWbkgAvV57i1agYy7o8NCFdGzRdzdBCqmkOqAvbnTgE-zjrryeWZGP6Ju3Dt36sUdXzro4ootsezcU-88R0rV7sC53WwfrsLMl0MfVq06H7E729aj69fVstVjOLn-cXyw-X84s43ycSWbqVmtsG-EkF8I0Atd1a9rO6rlpHTUto5JKIjg2VvMGGylZywuvrbWGHVWfHr3byQyuvR8OdFBb8IOGnUraq-dJ9L1apxvVUDrHTVME7_YCSL8nl0c1-GxdCDq6NGVFa0kwpzXBBX37H7pJE8TyvUKJRvAiZIV6_0hZSDmD6_4NQ7C6Xwr1ZCnYHbXxrss</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2679745093</pqid></control><display><type>article</type><title>Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Gelhard, Sarah ; Kestner, Roxane-Isabelle ; Armbrust, Moritz ; Steinmetz, Helmuth ; Foerch, Christian ; Bohmann, Ferdinand O.</creator><creatorcontrib>Gelhard, Sarah ; Kestner, Roxane-Isabelle ; Armbrust, Moritz ; Steinmetz, Helmuth ; Foerch, Christian ; Bohmann, Ferdinand O.</creatorcontrib><description>(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.</description><identifier>ISSN: 2077-0383</identifier><identifier>EISSN: 2077-0383</identifier><identifier>DOI: 10.3390/jcm11123343</identifier><identifier>PMID: 35743425</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Animals ; Clinical medicine ; Contraindications ; Diabetes ; Embolisms ; Glucose ; Heart attacks ; Hyperglycemia ; Ischemia ; Pulmonary arteries ; Stroke ; Symmetry ; Veins & arteries</subject><ispartof>Journal of clinical medicine, 2022-06, Vol.11 (12), p.3343</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c344t-83b6daa0c97e8477b97066dbdfca5bde2bd328281740bca490b883d4c97acccb3</cites><orcidid>0000-0001-5097-985X ; 0000-0001-6439-0667</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225099/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225099/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids></links><search><creatorcontrib>Gelhard, Sarah</creatorcontrib><creatorcontrib>Kestner, Roxane-Isabelle</creatorcontrib><creatorcontrib>Armbrust, Moritz</creatorcontrib><creatorcontrib>Steinmetz, Helmuth</creatorcontrib><creatorcontrib>Foerch, Christian</creatorcontrib><creatorcontrib>Bohmann, Ferdinand O.</creatorcontrib><title>Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia</title><title>Journal of clinical medicine</title><description>(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.</description><subject>Animals</subject><subject>Clinical medicine</subject><subject>Contraindications</subject><subject>Diabetes</subject><subject>Embolisms</subject><subject>Glucose</subject><subject>Heart attacks</subject><subject>Hyperglycemia</subject><subject>Ischemia</subject><subject>Pulmonary arteries</subject><subject>Stroke</subject><subject>Symmetry</subject><subject>Veins & arteries</subject><issn>2077-0383</issn><issn>2077-0383</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdkt9qFDEUhwdRbGl75QsEvBFkbf7tJOOFIGvtFqpCXa9DksnsZJtJ1pOZ1n0zH69pu0hrbk7C7zsfJ3Cq6g3BHxhr8OnGDoQQyhhnL6pDioWYYSbZyyf3g-ok5w0uR0pOiXhdHbC54IzT-WH19-zPNiTwcY0WKY6gfWy91aNPMaMuAVr1kAaTwi77_BFd-XyNUoeWbkgAvV57i1agYy7o8NCFdGzRdzdBCqmkOqAvbnTgE-zjrryeWZGP6Ju3Dt36sUdXzro4ootsezcU-88R0rV7sC53WwfrsLMl0MfVq06H7E729aj69fVstVjOLn-cXyw-X84s43ycSWbqVmtsG-EkF8I0Atd1a9rO6rlpHTUto5JKIjg2VvMGGylZywuvrbWGHVWfHr3byQyuvR8OdFBb8IOGnUraq-dJ9L1apxvVUDrHTVME7_YCSL8nl0c1-GxdCDq6NGVFa0kwpzXBBX37H7pJE8TyvUKJRvAiZIV6_0hZSDmD6_4NQ7C6Xwr1ZCnYHbXxrss</recordid><startdate>20220610</startdate><enddate>20220610</enddate><creator>Gelhard, Sarah</creator><creator>Kestner, Roxane-Isabelle</creator><creator>Armbrust, Moritz</creator><creator>Steinmetz, Helmuth</creator><creator>Foerch, Christian</creator><creator>Bohmann, Ferdinand O.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5097-985X</orcidid><orcidid>https://orcid.org/0000-0001-6439-0667</orcidid></search><sort><creationdate>20220610</creationdate><title>Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia</title><author>Gelhard, Sarah ; Kestner, Roxane-Isabelle ; Armbrust, Moritz ; Steinmetz, Helmuth ; Foerch, Christian ; Bohmann, Ferdinand O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-83b6daa0c97e8477b97066dbdfca5bde2bd328281740bca490b883d4c97acccb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Clinical medicine</topic><topic>Contraindications</topic><topic>Diabetes</topic><topic>Embolisms</topic><topic>Glucose</topic><topic>Heart attacks</topic><topic>Hyperglycemia</topic><topic>Ischemia</topic><topic>Pulmonary arteries</topic><topic>Stroke</topic><topic>Symmetry</topic><topic>Veins & arteries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gelhard, Sarah</creatorcontrib><creatorcontrib>Kestner, Roxane-Isabelle</creatorcontrib><creatorcontrib>Armbrust, Moritz</creatorcontrib><creatorcontrib>Steinmetz, Helmuth</creatorcontrib><creatorcontrib>Foerch, Christian</creatorcontrib><creatorcontrib>Bohmann, Ferdinand O.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gelhard, Sarah</au><au>Kestner, Roxane-Isabelle</au><au>Armbrust, Moritz</au><au>Steinmetz, Helmuth</au><au>Foerch, Christian</au><au>Bohmann, Ferdinand O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia</atitle><jtitle>Journal of clinical medicine</jtitle><date>2022-06-10</date><risdate>2022</risdate><volume>11</volume><issue>12</issue><spage>3343</spage><pages>3343-</pages><issn>2077-0383</issn><eissn>2077-0383</eissn><abstract>(1) Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke is limited because of several contraindications. In routine clinical practice, patients with a recent stroke are typically not treated with rt-PA in case of a recurrent ischemic event. The same applies to its use in the context of pulmonary artery embolism and myocardial infarction with a recent stroke. In this translational study, we evaluated whether rt-PA treatment after experimental ischemic stroke with or without additional hyperglycemia increases the risk for hemorrhagic transformation (HT) and worsens functional outcome regarding the old infarct area. (2) In total, 72 male C57BL/6N mice were used. Ischemic stroke (index stroke) was induced by transient middle cerebral artery occlusion (tMCAO). Mice received either rt-PA or saline 24 h or 14 days after index stroke to determine whether a recent ischemic stroke predisposes to HT. In addition to otherwise healthy mice, hyperglycemic mice were analyzed to evaluate diabetes as a second risk factor for HT. Mice designated to develop hyperglycemia were pre-treated with streptozotocin. (3) The neurological outcome in rt-PA and saline-treated normoglycemic mice did not differ significantly, either at 24 h or at 14 days. In contrast, hyperglycemic mice treated with rt-PA had a significantly worse neurological outcome (at 24 h, p = 0.02; at 14 days, p = 0.03). At 24 h after rt-PA or saline treatment, HT scores differed significantly (p = 0.02) with the highest scores within hyperglycemic mice treated with rt-PA, where notably only small petechial hemorrhages could be detected. (4) Thrombolysis after recent ischemic stroke does not increase the risk for HT or worsen the functional outcome in otherwise healthy mice. However, hyperglycemia as a second risk factor leads to neurological deterioration after rt-PA treatment, which cannot be explained by an increase of HT alone. Direct neurotoxic effects of rt-PA may play a role.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>35743425</pmid><doi>10.3390/jcm11123343</doi><orcidid>https://orcid.org/0000-0001-5097-985X</orcidid><orcidid>https://orcid.org/0000-0001-6439-0667</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2077-0383 |
ispartof | Journal of clinical medicine, 2022-06, Vol.11 (12), p.3343 |
issn | 2077-0383 2077-0383 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9225099 |
source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
subjects | Animals Clinical medicine Contraindications Diabetes Embolisms Glucose Heart attacks Hyperglycemia Ischemia Pulmonary arteries Stroke Symmetry Veins & arteries |
title | Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T02%3A09%3A18IST&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=Exploring%20Contraindications%20for%20Thrombolysis:%20Risk%20of%20Hemorrhagic%20Transformation%20and%20Neurological%20Deterioration%20after%20Thrombolysis%20in%20Mice%20with%20Recent%20Ischemic%20Stroke%20and%20Hyperglycemia&rft.jtitle=Journal%20of%20clinical%20medicine&rft.au=Gelhard,%20Sarah&rft.date=2022-06-10&rft.volume=11&rft.issue=12&rft.spage=3343&rft.pages=3343-&rft.issn=2077-0383&rft.eissn=2077-0383&rft_id=info:doi/10.3390/jcm11123343&rft_dat=%3Cproquest_pubme%3E2681042610%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=2679745093&rft_id=info:pmid/35743425&rfr_iscdi=true |