Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans
OBJECTIVES This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty. BACKGROUND Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a re...
Gespeichert in:
| Veröffentlicht in: | Journal of the American College of Cardiology 2000-03, Vol.35 (3), p.583-591 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 591 |
|---|---|
| container_issue | 3 |
| container_start_page | 583 |
| container_title | Journal of the American College of Cardiology |
| container_volume | 35 |
| creator | Lehmann, Kenneth G Popma, Jeffrey J Werner, Jeffrey A Lansky, Alexandra J Wilensky, Robert L |
| description | OBJECTIVES
This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty.
BACKGROUND
Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models.
METHODS
In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon.
RESULTS
The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 ± 0.44 vs. 1.49 ± 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables.
CONCLUSIONS
Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis. |
| doi_str_mv | 10.1016/S0735-1097(99)00603-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70945870</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0735109799006038</els_id><sourcerecordid>70945870</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-6c6fda1a1e9e5ed3da9429fd4e95601ea73086e79387bebacb84b33118dbd08c3</originalsourceid><addsrcrecordid>eNqFkEtv1DAQgK0K1C6lP6HIB1TBIWDXSWyfqlLxkipxAHq1Jvaka-TYi51U2n-Pt7sq3DiNNPPN6yPknLN3nPH-_XcmRddwpuUbrd8y1jPRqCOy4l2nGtFp-YysnpAT8qKUX6xSiutjcsKZ5H3bqRWBOyh2CZBpxik5DD7eU4iOzmukIVkIdJd8wLylaaR2Oye7hgDFR_qBwjhjpjblFKECEO992tTivKW1vl4miOUleT5CKHh2iKfk56ePP26-NLffPn-9ub5tbKvZ3PS2Hx1w4KixQycc6PZSj65F3fWMI0jBVI9SCyUHHMAOqh2E4Fy5wTFlxSm52M_d5PR7wTKbyReLIUDEtBQjma4fS1bBbg_anErJOJpN9lO933Bmdm7No1uzE2e0No9ujap9rw4LlmFC90_XXmYFXh-A6hTCmCFaX_5yl0orJSp2tcew2njwmE2xHqNF5zPa2bjk_3PJH865l4o</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70945870</pqid></control><display><type>article</type><title>Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Lehmann, Kenneth G ; Popma, Jeffrey J ; Werner, Jeffrey A ; Lansky, Alexandra J ; Wilensky, Robert L</creator><creatorcontrib>Lehmann, Kenneth G ; Popma, Jeffrey J ; Werner, Jeffrey A ; Lansky, Alexandra J ; Wilensky, Robert L</creatorcontrib><description>OBJECTIVES
This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty.
BACKGROUND
Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models.
METHODS
In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon.
RESULTS
The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 ± 0.44 vs. 1.49 ± 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables.
CONCLUSIONS
Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/S0735-1097(99)00603-8</identifier><identifier>PMID: 10716458</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; Biological and medical sciences ; Catheterization, Peripheral ; Coronary Angiography ; Coronary Disease - diagnostic imaging ; Coronary Disease - therapy ; Coronary Vessels - drug effects ; Cytochalasin B - administration & dosage ; Cytochalasin B - therapeutic use ; Drug Delivery Systems - methods ; Electrocardiography ; Feasibility Studies ; Female ; General and cellular metabolism. Vitamins ; Humans ; Infusions, Intra-Arterial - methods ; Male ; Medical sciences ; Middle Aged ; Myocardial Revascularization ; Pharmacology. Drug treatments ; Safety ; Treatment Outcome</subject><ispartof>Journal of the American College of Cardiology, 2000-03, Vol.35 (3), p.583-591</ispartof><rights>2000 American College of Cardiology</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-6c6fda1a1e9e5ed3da9429fd4e95601ea73086e79387bebacb84b33118dbd08c3</citedby><cites>FETCH-LOGICAL-c490t-6c6fda1a1e9e5ed3da9429fd4e95601ea73086e79387bebacb84b33118dbd08c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0735109799006038$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1289883$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10716458$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lehmann, Kenneth G</creatorcontrib><creatorcontrib>Popma, Jeffrey J</creatorcontrib><creatorcontrib>Werner, Jeffrey A</creatorcontrib><creatorcontrib>Lansky, Alexandra J</creatorcontrib><creatorcontrib>Wilensky, Robert L</creatorcontrib><title>Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>OBJECTIVES
This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty.
BACKGROUND
Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models.
METHODS
In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon.
RESULTS
The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 ± 0.44 vs. 1.49 ± 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables.
CONCLUSIONS
Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angioplasty, Balloon, Coronary</subject><subject>Biological and medical sciences</subject><subject>Catheterization, Peripheral</subject><subject>Coronary Angiography</subject><subject>Coronary Disease - diagnostic imaging</subject><subject>Coronary Disease - therapy</subject><subject>Coronary Vessels - drug effects</subject><subject>Cytochalasin B - administration & dosage</subject><subject>Cytochalasin B - therapeutic use</subject><subject>Drug Delivery Systems - methods</subject><subject>Electrocardiography</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Infusions, Intra-Arterial - methods</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Revascularization</subject><subject>Pharmacology. Drug treatments</subject><subject>Safety</subject><subject>Treatment Outcome</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtv1DAQgK0K1C6lP6HIB1TBIWDXSWyfqlLxkipxAHq1Jvaka-TYi51U2n-Pt7sq3DiNNPPN6yPknLN3nPH-_XcmRddwpuUbrd8y1jPRqCOy4l2nGtFp-YysnpAT8qKUX6xSiutjcsKZ5H3bqRWBOyh2CZBpxik5DD7eU4iOzmukIVkIdJd8wLylaaR2Oye7hgDFR_qBwjhjpjblFKECEO992tTivKW1vl4miOUleT5CKHh2iKfk56ePP26-NLffPn-9ub5tbKvZ3PS2Hx1w4KixQycc6PZSj65F3fWMI0jBVI9SCyUHHMAOqh2E4Fy5wTFlxSm52M_d5PR7wTKbyReLIUDEtBQjma4fS1bBbg_anErJOJpN9lO933Bmdm7No1uzE2e0No9ujap9rw4LlmFC90_XXmYFXh-A6hTCmCFaX_5yl0orJSp2tcew2njwmE2xHqNF5zPa2bjk_3PJH865l4o</recordid><startdate>20000301</startdate><enddate>20000301</enddate><creator>Lehmann, Kenneth G</creator><creator>Popma, Jeffrey J</creator><creator>Werner, Jeffrey A</creator><creator>Lansky, Alexandra J</creator><creator>Wilensky, Robert L</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>20000301</creationdate><title>Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans</title><author>Lehmann, Kenneth G ; Popma, Jeffrey J ; Werner, Jeffrey A ; Lansky, Alexandra J ; Wilensky, Robert L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-6c6fda1a1e9e5ed3da9429fd4e95601ea73086e79387bebacb84b33118dbd08c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angioplasty, Balloon, Coronary</topic><topic>Biological and medical sciences</topic><topic>Catheterization, Peripheral</topic><topic>Coronary Angiography</topic><topic>Coronary Disease - diagnostic imaging</topic><topic>Coronary Disease - therapy</topic><topic>Coronary Vessels - drug effects</topic><topic>Cytochalasin B - administration & dosage</topic><topic>Cytochalasin B - therapeutic use</topic><topic>Drug Delivery Systems - methods</topic><topic>Electrocardiography</topic><topic>Feasibility Studies</topic><topic>Female</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Infusions, Intra-Arterial - methods</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Myocardial Revascularization</topic><topic>Pharmacology. Drug treatments</topic><topic>Safety</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lehmann, Kenneth G</creatorcontrib><creatorcontrib>Popma, Jeffrey J</creatorcontrib><creatorcontrib>Werner, Jeffrey A</creatorcontrib><creatorcontrib>Lansky, Alexandra J</creatorcontrib><creatorcontrib>Wilensky, Robert L</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><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 the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lehmann, Kenneth G</au><au>Popma, Jeffrey J</au><au>Werner, Jeffrey A</au><au>Lansky, Alexandra J</au><au>Wilensky, Robert L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2000-03-01</date><risdate>2000</risdate><volume>35</volume><issue>3</issue><spage>583</spage><epage>591</epage><pages>583-591</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><abstract>OBJECTIVES
This study sought to determine the safety, feasibility and outcome of local delivery of cytochalasin B at the site of coronary angioplasty.
BACKGROUND
Previous failures in the pharmacologic prevention of restenosis may have been related to inadequate dosing at the angioplasty site as a result of systemic drug administration. Alternatively, although previous experimental protocols have typically targeted control of excess tissue growth (intimal hyperplasia), it now appears that overall arterial constriction (vascular remodeling) is the major contributor to late lumen loss. Cytochalasin B inhibits the polymerization of actin and has proved to be a potent inhibitor of vascular remodeling in animal models.
METHODS
In this phase I, multicenter, randomized, controlled trial, cytochalasin B (or matching placebo) was administered to the site of a successful balloon angioplasty using a microporous local delivery infusion balloon.
RESULTS
The rate of drug delivery at a constant infusion pressure varied significantly from patient to patient (range 1.7 to 20.2 ml/min), perhaps related to a variable constricting effect of the atherosclerotic plaque on the infusion balloon. The minimal stenosis diameter after the procedure was slightly better in the active drug group (1.86 ± 0.44 vs. 1.49 ± 0.63 mm, p < 0.03), but this difference was not seen at four to six weeks. Although the study was not powered for clinical outcomes (n = 43), the combined end point (death, nonfatal infarction or repeat revascularization) was encountered in 20% of the patients receiving cytochalasin B and in 38% of the patients receiving placebo. Clinical restenosis occurred in 18% of the treatment group and 22% of the placebo group. There were no significant differences between groups in biochemical or electrocardiographic variables.
CONCLUSIONS
Cytochalasin B can be safely administered by local delivery after successful coronary angioplasty and warrants further study of its efficacy in reducing restenosis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10716458</pmid><doi>10.1016/S0735-1097(99)00603-8</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0735-1097 |
| ispartof | Journal of the American College of Cardiology, 2000-03, Vol.35 (3), p.583-591 |
| issn | 0735-1097 1558-3597 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70945870 |
| source | MEDLINE; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Angioplasty, Balloon, Coronary Biological and medical sciences Catheterization, Peripheral Coronary Angiography Coronary Disease - diagnostic imaging Coronary Disease - therapy Coronary Vessels - drug effects Cytochalasin B - administration & dosage Cytochalasin B - therapeutic use Drug Delivery Systems - methods Electrocardiography Feasibility Studies Female General and cellular metabolism. Vitamins Humans Infusions, Intra-Arterial - methods Male Medical sciences Middle Aged Myocardial Revascularization Pharmacology. Drug treatments Safety Treatment Outcome |
| title | Vascular remodeling and the local delivery of cytochalasin B after coronary angioplasty in humans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T20%3A26%3A13IST&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=Vascular%20remodeling%20and%20the%20local%20delivery%20of%20cytochalasin%20B%20after%20coronary%20angioplasty%20in%20humans&rft.jtitle=Journal%20of%20the%20American%20College%20of%20Cardiology&rft.au=Lehmann,%20Kenneth%20G&rft.date=2000-03-01&rft.volume=35&rft.issue=3&rft.spage=583&rft.epage=591&rft.pages=583-591&rft.issn=0735-1097&rft.eissn=1558-3597&rft.coden=JACCDI&rft_id=info:doi/10.1016/S0735-1097(99)00603-8&rft_dat=%3Cproquest_cross%3E70945870%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=70945870&rft_id=info:pmid/10716458&rft_els_id=S0735109799006038&rfr_iscdi=true |