Clinically relevant concentration of propofol and benzodiazepines did not affect in vitro angiogenesis

Purpose Angiogenesis, one of regenerative medicine, is essential in the process of wound healing. The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capill...

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Veröffentlicht in:Journal of anesthesia 2021-12, Vol.35 (6), p.870-878
Hauptverfasser: Takaishi, Kazumi, Kudo, Yasusei, Kawahito, Shinji, Kitahata, Hiroshi
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container_title Journal of anesthesia
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creator Takaishi, Kazumi
Kudo, Yasusei
Kawahito, Shinji
Kitahata, Hiroshi
description Purpose Angiogenesis, one of regenerative medicine, is essential in the process of wound healing. The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capillary tube formation. Methods The effects of midazolam, diazepam and propofol (1, 10, 50 µM each) on proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF) were determined. Quantitation of migration was achieved by measuring the fluorescence of migrating HUVEC using angiogenesis system. The effects of midazolam, diazepam and propofol on in vitro angiogenesis were investigated in co-cultured HUVEC and NHDF incubated. The effects of midazolam on activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases were examined by Western blot analysis using phospho-specific antibodies. Parametric data were analyzed with one-way repeated measures analysis of variance followed by the Scheffé test. A value of P  
doi_str_mv 10.1007/s00540-021-02993-x
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The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capillary tube formation. Methods The effects of midazolam, diazepam and propofol (1, 10, 50 µM each) on proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF) were determined. Quantitation of migration was achieved by measuring the fluorescence of migrating HUVEC using angiogenesis system. The effects of midazolam, diazepam and propofol on in vitro angiogenesis were investigated in co-cultured HUVEC and NHDF incubated. The effects of midazolam on activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases were examined by Western blot analysis using phospho-specific antibodies. Parametric data were analyzed with one-way repeated measures analysis of variance followed by the Scheffé test. A value of P  &lt; 0.05 was considered statistically significant. Results Fifty µM of midazolam significantly impaired endothelial cell proliferation, migration, and in vitro capillary tube formation. Propofol, diazepam or lower dose midazolam did not show any enhancing or suppressive effects on in vitro angiogenesis. Fifty µM of midazolam remarkably activated ERK, but not p38 MAPK in HUVEC. Conclusion Propofol and benzodiazepines except high-dose midazolam did not affect in vitro angiogenesis. High-dose midazolam may impair in vitro capillary tube formation due to by suppressing proliferation and migration of endothelial cells via activation of ERK.</description><identifier>ISSN: 0913-8668</identifier><identifier>EISSN: 1438-8359</identifier><identifier>DOI: 10.1007/s00540-021-02993-x</identifier><identifier>PMID: 34460008</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Analysis ; Anesthesiology ; Anesthetics ; Anesthetics, Intravenous ; Antibodies ; Aprotinin ; Benzodiazepines ; Critical Care Medicine ; Diazepam ; Emergency Medicine ; Endothelium ; Ethylenediaminetetraacetic acid ; Fluorescence ; Human Umbilical Vein Endothelial Cells ; Humans ; Intensive ; Medicine ; Medicine &amp; Public Health ; Midazolam ; Mitogens ; Original Article ; Pain Medicine ; Phenols ; Propofol - pharmacology ; Protein kinases ; Suramin sodium ; Textile industry ; Viral antibodies</subject><ispartof>Journal of anesthesia, 2021-12, Vol.35 (6), p.870-878</ispartof><rights>Japanese Society of Anesthesiologists 2021</rights><rights>2021. Japanese Society of Anesthesiologists.</rights><rights>COPYRIGHT 2021 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c427t-184ba63a826cc334792417d4817d913cb38666ad476a119e29a497566dd5f583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00540-021-02993-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00540-021-02993-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34460008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takaishi, Kazumi</creatorcontrib><creatorcontrib>Kudo, Yasusei</creatorcontrib><creatorcontrib>Kawahito, Shinji</creatorcontrib><creatorcontrib>Kitahata, Hiroshi</creatorcontrib><title>Clinically relevant concentration of propofol and benzodiazepines did not affect in vitro angiogenesis</title><title>Journal of anesthesia</title><addtitle>J Anesth</addtitle><addtitle>J Anesth</addtitle><description>Purpose Angiogenesis, one of regenerative medicine, is essential in the process of wound healing. The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capillary tube formation. Methods The effects of midazolam, diazepam and propofol (1, 10, 50 µM each) on proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF) were determined. Quantitation of migration was achieved by measuring the fluorescence of migrating HUVEC using angiogenesis system. The effects of midazolam, diazepam and propofol on in vitro angiogenesis were investigated in co-cultured HUVEC and NHDF incubated. The effects of midazolam on activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases were examined by Western blot analysis using phospho-specific antibodies. Parametric data were analyzed with one-way repeated measures analysis of variance followed by the Scheffé test. A value of P  &lt; 0.05 was considered statistically significant. Results Fifty µM of midazolam significantly impaired endothelial cell proliferation, migration, and in vitro capillary tube formation. Propofol, diazepam or lower dose midazolam did not show any enhancing or suppressive effects on in vitro angiogenesis. Fifty µM of midazolam remarkably activated ERK, but not p38 MAPK in HUVEC. Conclusion Propofol and benzodiazepines except high-dose midazolam did not affect in vitro angiogenesis. High-dose midazolam may impair in vitro capillary tube formation due to by suppressing proliferation and migration of endothelial cells via activation of ERK.</description><subject>Analysis</subject><subject>Anesthesiology</subject><subject>Anesthetics</subject><subject>Anesthetics, Intravenous</subject><subject>Antibodies</subject><subject>Aprotinin</subject><subject>Benzodiazepines</subject><subject>Critical Care Medicine</subject><subject>Diazepam</subject><subject>Emergency Medicine</subject><subject>Endothelium</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Fluorescence</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Intensive</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Midazolam</subject><subject>Mitogens</subject><subject>Original Article</subject><subject>Pain Medicine</subject><subject>Phenols</subject><subject>Propofol - pharmacology</subject><subject>Protein kinases</subject><subject>Suramin sodium</subject><subject>Textile industry</subject><subject>Viral antibodies</subject><issn>0913-8668</issn><issn>1438-8359</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV9rHCEUxaW0NNttv0AfitCXvkyqo-M4j2HpPwj0Je_i6nUxuLrV2ZDk0-duJy0UliIq6u9cPPcQ8p6zS87Y-LkxNkjWsZ7jnCbR3b8gKy6F7rQYppdkxSYuOq2UviBvWrtljCnOxWtyIaRUeNIrEjYp5uhsSg-0QoI7m2fqSnaQ52rnWDItgR5qOZRQErXZ0y3kx-KjfYRDzNCoj57mMlMbAriZxkzv4lwLsrtYdoBIbG_Jq2BTg3fP-5rcfP1ys_neXf_89mNzdd052Y9zx7XcWiWs7pVzQshx6iUfvdS4oBe3FehGWS9HZTmfoJ-snMZBKe-HMGixJp-WsvjhX0dos9nH5iAlm6Ecm-kR7RVX2KQ1-bigO5vAxBwK-nUn3Fwp3etByYkh1Z2hTqaqTSVDiHj9D395hsfhYR_dWUG_CFwtrVUI5lDj3tYHw5k5pWyWlA2mbH6nbO5R9OHZ5nG7B_9X8idWBMQCNHzKO6jmthxrxs7_r-wTnhSxxw</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Takaishi, Kazumi</creator><creator>Kudo, Yasusei</creator><creator>Kawahito, Shinji</creator><creator>Kitahata, Hiroshi</creator><general>Springer Singapore</general><general>Springer</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20211201</creationdate><title>Clinically relevant concentration of propofol and benzodiazepines did not affect in vitro angiogenesis</title><author>Takaishi, Kazumi ; Kudo, Yasusei ; Kawahito, Shinji ; Kitahata, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-184ba63a826cc334792417d4817d913cb38666ad476a119e29a497566dd5f583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Anesthesiology</topic><topic>Anesthetics</topic><topic>Anesthetics, Intravenous</topic><topic>Antibodies</topic><topic>Aprotinin</topic><topic>Benzodiazepines</topic><topic>Critical Care Medicine</topic><topic>Diazepam</topic><topic>Emergency Medicine</topic><topic>Endothelium</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Fluorescence</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Intensive</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Midazolam</topic><topic>Mitogens</topic><topic>Original Article</topic><topic>Pain Medicine</topic><topic>Phenols</topic><topic>Propofol - pharmacology</topic><topic>Protein kinases</topic><topic>Suramin sodium</topic><topic>Textile industry</topic><topic>Viral antibodies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takaishi, Kazumi</creatorcontrib><creatorcontrib>Kudo, Yasusei</creatorcontrib><creatorcontrib>Kawahito, Shinji</creatorcontrib><creatorcontrib>Kitahata, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of anesthesia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takaishi, Kazumi</au><au>Kudo, Yasusei</au><au>Kawahito, Shinji</au><au>Kitahata, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinically relevant concentration of propofol and benzodiazepines did not affect in vitro angiogenesis</atitle><jtitle>Journal of anesthesia</jtitle><stitle>J Anesth</stitle><addtitle>J Anesth</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>35</volume><issue>6</issue><spage>870</spage><epage>878</epage><pages>870-878</pages><issn>0913-8668</issn><eissn>1438-8359</eissn><abstract>Purpose Angiogenesis, one of regenerative medicine, is essential in the process of wound healing. The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capillary tube formation. Methods The effects of midazolam, diazepam and propofol (1, 10, 50 µM each) on proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF) were determined. Quantitation of migration was achieved by measuring the fluorescence of migrating HUVEC using angiogenesis system. The effects of midazolam, diazepam and propofol on in vitro angiogenesis were investigated in co-cultured HUVEC and NHDF incubated. The effects of midazolam on activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases were examined by Western blot analysis using phospho-specific antibodies. Parametric data were analyzed with one-way repeated measures analysis of variance followed by the Scheffé test. A value of P  &lt; 0.05 was considered statistically significant. Results Fifty µM of midazolam significantly impaired endothelial cell proliferation, migration, and in vitro capillary tube formation. Propofol, diazepam or lower dose midazolam did not show any enhancing or suppressive effects on in vitro angiogenesis. Fifty µM of midazolam remarkably activated ERK, but not p38 MAPK in HUVEC. Conclusion Propofol and benzodiazepines except high-dose midazolam did not affect in vitro angiogenesis. High-dose midazolam may impair in vitro capillary tube formation due to by suppressing proliferation and migration of endothelial cells via activation of ERK.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>34460008</pmid><doi>10.1007/s00540-021-02993-x</doi><tpages>9</tpages></addata></record>
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subjects Analysis
Anesthesiology
Anesthetics
Anesthetics, Intravenous
Antibodies
Aprotinin
Benzodiazepines
Critical Care Medicine
Diazepam
Emergency Medicine
Endothelium
Ethylenediaminetetraacetic acid
Fluorescence
Human Umbilical Vein Endothelial Cells
Humans
Intensive
Medicine
Medicine & Public Health
Midazolam
Mitogens
Original Article
Pain Medicine
Phenols
Propofol - pharmacology
Protein kinases
Suramin sodium
Textile industry
Viral antibodies
title Clinically relevant concentration of propofol and benzodiazepines did not affect in vitro angiogenesis
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