Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters
The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2002-07, Vol.106 (5), p.613-619 |
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| creator | MATSUMOTO, Yasunori AIHARA, Hajime YAMAUCHI-KOHNO, Rikako REIEN, Yoshie OGURA, Takehiko YABANA, Hideo MASUDA, Yoshiaki SATO, Toshiaki KOMURO, Issei NAKAYA, Haruaki |
| description | The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of long-term ET(A) receptor blockade on the electrophysiological properties of ventricular cells, the surface ECG, and the survival in BIO 14.6 cardiomyopathic hamsters.
Membrane currents and action potentials were recorded from left ventricular cells isolated from normal F1beta hamsters and cardiomyopathic BIO 14.6 hamsters untreated and chronically treated with TA-0201, an ET(A) receptor antagonist. In ventricular cells of untreated BIO 14.6 hamsters, the action potential duration was prolonged and the densities of the L-type Ca2+ current (I(Ca,L)), the transient outward current (I(to)), the delayed rectifier K+ current (I(K)), and the inward rectifier K+ current (I(K1)) were decreased compared with those of F1beta hamsters. Long-term treatment with the ET(A) receptor antagonist significantly attenuated action potential duration prolongation and reduction of I(to), I(K), and I(Ca,L) in BIO 14.6 ventricular cells. Long-term ET(A) receptor blockade prevented the QT prolongation and ventricular arrhythmias and improved the survival rate in the cardiomyopathic hamsters.
Long-term treatment with an ET(A) antagonist inhibits electrical remodeling such as downregulation of K+ and Ca2+ currents, action potential prolongation, and the increased QT interval and thereby suppresses ventricular arrhythmias in cardiomyopathic hearts. ET(A) receptor blockade may provide a new strategy for the prevention of ventricular arrhythmias associated with heart failure. |
| doi_str_mv | 10.1161/01.CIR.0000023526.45800.8E |
| format | Article |
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Membrane currents and action potentials were recorded from left ventricular cells isolated from normal F1beta hamsters and cardiomyopathic BIO 14.6 hamsters untreated and chronically treated with TA-0201, an ET(A) receptor antagonist. In ventricular cells of untreated BIO 14.6 hamsters, the action potential duration was prolonged and the densities of the L-type Ca2+ current (I(Ca,L)), the transient outward current (I(to)), the delayed rectifier K+ current (I(K)), and the inward rectifier K+ current (I(K1)) were decreased compared with those of F1beta hamsters. Long-term treatment with the ET(A) receptor antagonist significantly attenuated action potential duration prolongation and reduction of I(to), I(K), and I(Ca,L) in BIO 14.6 ventricular cells. Long-term ET(A) receptor blockade prevented the QT prolongation and ventricular arrhythmias and improved the survival rate in the cardiomyopathic hamsters.
Long-term treatment with an ET(A) antagonist inhibits electrical remodeling such as downregulation of K+ and Ca2+ currents, action potential prolongation, and the increased QT interval and thereby suppresses ventricular arrhythmias in cardiomyopathic hearts. ET(A) receptor blockade may provide a new strategy for the prevention of ventricular arrhythmias associated with heart failure.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.0000023526.45800.8E</identifier><identifier>PMID: 12147545</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Action Potentials - drug effects ; Action Potentials - physiology ; Animals ; Antiarythmic agents ; Biological and medical sciences ; Calcium - metabolism ; Calcium Channels, L-Type - metabolism ; Cardiomyopathies - drug therapy ; Cardiomyopathies - physiopathology ; Cardiovascular system ; Chronic Disease ; Cricetinae ; Disease Models, Animal ; Electrocardiography - drug effects ; Electrophysiologic Techniques, Cardiac ; Endothelin Receptor Antagonists ; Heart Conduction System - drug effects ; Heart Conduction System - physiopathology ; Heart Ventricles - cytology ; Heart Ventricles - drug effects ; Heart Ventricles - physiopathology ; Male ; Medical sciences ; Myocardium - cytology ; Patch-Clamp Techniques ; Pharmacology. Drug treatments ; Potassium Channels, Inwardly Rectifying - metabolism ; Pyrimidines - therapeutic use ; Receptor, Endothelin A ; Sulfonamides - therapeutic use ; Survival Rate ; Time</subject><ispartof>Circulation (New York, N.Y.), 2002-07, Vol.106 (5), p.613-619</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-2efa44319abe9f6708afaebcfc1599f1de9e97377a9de60adf86ccd82d00a9f13</citedby><cites>FETCH-LOGICAL-c504t-2efa44319abe9f6708afaebcfc1599f1de9e97377a9de60adf86ccd82d00a9f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13836475$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12147545$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MATSUMOTO, Yasunori</creatorcontrib><creatorcontrib>AIHARA, Hajime</creatorcontrib><creatorcontrib>YAMAUCHI-KOHNO, Rikako</creatorcontrib><creatorcontrib>REIEN, Yoshie</creatorcontrib><creatorcontrib>OGURA, Takehiko</creatorcontrib><creatorcontrib>YABANA, Hideo</creatorcontrib><creatorcontrib>MASUDA, Yoshiaki</creatorcontrib><creatorcontrib>SATO, Toshiaki</creatorcontrib><creatorcontrib>KOMURO, Issei</creatorcontrib><creatorcontrib>NAKAYA, Haruaki</creatorcontrib><title>Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of long-term ET(A) receptor blockade on the electrophysiological properties of ventricular cells, the surface ECG, and the survival in BIO 14.6 cardiomyopathic hamsters.
Membrane currents and action potentials were recorded from left ventricular cells isolated from normal F1beta hamsters and cardiomyopathic BIO 14.6 hamsters untreated and chronically treated with TA-0201, an ET(A) receptor antagonist. In ventricular cells of untreated BIO 14.6 hamsters, the action potential duration was prolonged and the densities of the L-type Ca2+ current (I(Ca,L)), the transient outward current (I(to)), the delayed rectifier K+ current (I(K)), and the inward rectifier K+ current (I(K1)) were decreased compared with those of F1beta hamsters. Long-term treatment with the ET(A) receptor antagonist significantly attenuated action potential duration prolongation and reduction of I(to), I(K), and I(Ca,L) in BIO 14.6 ventricular cells. Long-term ET(A) receptor blockade prevented the QT prolongation and ventricular arrhythmias and improved the survival rate in the cardiomyopathic hamsters.
Long-term treatment with an ET(A) antagonist inhibits electrical remodeling such as downregulation of K+ and Ca2+ currents, action potential prolongation, and the increased QT interval and thereby suppresses ventricular arrhythmias in cardiomyopathic hearts. ET(A) receptor blockade may provide a new strategy for the prevention of ventricular arrhythmias associated with heart failure.</description><subject>Action Potentials - drug effects</subject><subject>Action Potentials - physiology</subject><subject>Animals</subject><subject>Antiarythmic agents</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium Channels, L-Type - metabolism</subject><subject>Cardiomyopathies - drug therapy</subject><subject>Cardiomyopathies - physiopathology</subject><subject>Cardiovascular system</subject><subject>Chronic Disease</subject><subject>Cricetinae</subject><subject>Disease Models, Animal</subject><subject>Electrocardiography - drug effects</subject><subject>Electrophysiologic Techniques, Cardiac</subject><subject>Endothelin Receptor Antagonists</subject><subject>Heart Conduction System - drug effects</subject><subject>Heart Conduction System - physiopathology</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - drug effects</subject><subject>Heart Ventricles - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Myocardium - cytology</subject><subject>Patch-Clamp Techniques</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channels, Inwardly Rectifying - metabolism</subject><subject>Pyrimidines - therapeutic use</subject><subject>Receptor, Endothelin A</subject><subject>Sulfonamides - therapeutic use</subject><subject>Survival Rate</subject><subject>Time</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE2LFDEQhoMo7uzqX5BG0Fu3-ex0vMkwugsDgug5VCeVnWh3Z0x6DvvvzbgDU5dQvM9bgYeQ94x2jPXsE2Xd9uFHR8_DheJ9J9VAaTfsXpANU1y2UgnzkmxqblotOL8ht6X8rmsvtHpNbhhnUiupNsTt0_LYrpjnBhef1gNOcWmgyejwuKbcjFNyf8BjE5dDHONaGpzQrTk6mCo1J39uPNa4cZB9TPNTOsJ6iK45wFzq5fKGvAowFXx7ee_Ir6-7n9v7dv_928P2y751isq15RhASsEMjGhCr-kAAXB0wTFlTGAeDRottAbjsafgw9A75wfuKYWaizvy8fnuMae_JyyrnWNxOE2wYDoVq5mRg-Z9BT8_gy6nUjIGe8xxhvxkGbVnxZYyWxXbq2L7X7EddrX87vLLaZzRX6sXpxX4cAGgVEkhw-JiuXJiEH0lxT9-4IfO</recordid><startdate>20020730</startdate><enddate>20020730</enddate><creator>MATSUMOTO, Yasunori</creator><creator>AIHARA, Hajime</creator><creator>YAMAUCHI-KOHNO, Rikako</creator><creator>REIEN, Yoshie</creator><creator>OGURA, Takehiko</creator><creator>YABANA, Hideo</creator><creator>MASUDA, Yoshiaki</creator><creator>SATO, Toshiaki</creator><creator>KOMURO, Issei</creator><creator>NAKAYA, Haruaki</creator><general>Lippincott Williams & Wilkins</general><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>20020730</creationdate><title>Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters</title><author>MATSUMOTO, Yasunori ; AIHARA, Hajime ; YAMAUCHI-KOHNO, Rikako ; REIEN, Yoshie ; OGURA, Takehiko ; YABANA, Hideo ; MASUDA, Yoshiaki ; SATO, Toshiaki ; KOMURO, Issei ; NAKAYA, Haruaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-2efa44319abe9f6708afaebcfc1599f1de9e97377a9de60adf86ccd82d00a9f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Action Potentials - drug effects</topic><topic>Action Potentials - physiology</topic><topic>Animals</topic><topic>Antiarythmic agents</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Channels, L-Type - metabolism</topic><topic>Cardiomyopathies - drug therapy</topic><topic>Cardiomyopathies - physiopathology</topic><topic>Cardiovascular system</topic><topic>Chronic Disease</topic><topic>Cricetinae</topic><topic>Disease Models, Animal</topic><topic>Electrocardiography - drug effects</topic><topic>Electrophysiologic Techniques, Cardiac</topic><topic>Endothelin Receptor Antagonists</topic><topic>Heart Conduction System - drug effects</topic><topic>Heart Conduction System - physiopathology</topic><topic>Heart Ventricles - cytology</topic><topic>Heart Ventricles - drug effects</topic><topic>Heart Ventricles - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Myocardium - cytology</topic><topic>Patch-Clamp Techniques</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channels, Inwardly Rectifying - metabolism</topic><topic>Pyrimidines - therapeutic use</topic><topic>Receptor, Endothelin A</topic><topic>Sulfonamides - therapeutic use</topic><topic>Survival Rate</topic><topic>Time</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MATSUMOTO, Yasunori</creatorcontrib><creatorcontrib>AIHARA, Hajime</creatorcontrib><creatorcontrib>YAMAUCHI-KOHNO, Rikako</creatorcontrib><creatorcontrib>REIEN, Yoshie</creatorcontrib><creatorcontrib>OGURA, Takehiko</creatorcontrib><creatorcontrib>YABANA, Hideo</creatorcontrib><creatorcontrib>MASUDA, Yoshiaki</creatorcontrib><creatorcontrib>SATO, Toshiaki</creatorcontrib><creatorcontrib>KOMURO, Issei</creatorcontrib><creatorcontrib>NAKAYA, Haruaki</creatorcontrib><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>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MATSUMOTO, Yasunori</au><au>AIHARA, Hajime</au><au>YAMAUCHI-KOHNO, Rikako</au><au>REIEN, Yoshie</au><au>OGURA, Takehiko</au><au>YABANA, Hideo</au><au>MASUDA, Yoshiaki</au><au>SATO, Toshiaki</au><au>KOMURO, Issei</au><au>NAKAYA, Haruaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2002-07-30</date><risdate>2002</risdate><volume>106</volume><issue>5</issue><spage>613</spage><epage>619</epage><pages>613-619</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The endothelin (ET) system is activated in failing hearts. Congestive heart failure frequently is associated with ventricular arrhythmias, which may result from electrical remodeling such as changes of ionic current density and heterogeneous action potential prolongation. We examined the effects of long-term ET(A) receptor blockade on the electrophysiological properties of ventricular cells, the surface ECG, and the survival in BIO 14.6 cardiomyopathic hamsters.
Membrane currents and action potentials were recorded from left ventricular cells isolated from normal F1beta hamsters and cardiomyopathic BIO 14.6 hamsters untreated and chronically treated with TA-0201, an ET(A) receptor antagonist. In ventricular cells of untreated BIO 14.6 hamsters, the action potential duration was prolonged and the densities of the L-type Ca2+ current (I(Ca,L)), the transient outward current (I(to)), the delayed rectifier K+ current (I(K)), and the inward rectifier K+ current (I(K1)) were decreased compared with those of F1beta hamsters. Long-term treatment with the ET(A) receptor antagonist significantly attenuated action potential duration prolongation and reduction of I(to), I(K), and I(Ca,L) in BIO 14.6 ventricular cells. Long-term ET(A) receptor blockade prevented the QT prolongation and ventricular arrhythmias and improved the survival rate in the cardiomyopathic hamsters.
Long-term treatment with an ET(A) antagonist inhibits electrical remodeling such as downregulation of K+ and Ca2+ currents, action potential prolongation, and the increased QT interval and thereby suppresses ventricular arrhythmias in cardiomyopathic hearts. ET(A) receptor blockade may provide a new strategy for the prevention of ventricular arrhythmias associated with heart failure.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12147545</pmid><doi>10.1161/01.CIR.0000023526.45800.8E</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Action Potentials - drug effects Action Potentials - physiology Animals Antiarythmic agents Biological and medical sciences Calcium - metabolism Calcium Channels, L-Type - metabolism Cardiomyopathies - drug therapy Cardiomyopathies - physiopathology Cardiovascular system Chronic Disease Cricetinae Disease Models, Animal Electrocardiography - drug effects Electrophysiologic Techniques, Cardiac Endothelin Receptor Antagonists Heart Conduction System - drug effects Heart Conduction System - physiopathology Heart Ventricles - cytology Heart Ventricles - drug effects Heart Ventricles - physiopathology Male Medical sciences Myocardium - cytology Patch-Clamp Techniques Pharmacology. Drug treatments Potassium Channels, Inwardly Rectifying - metabolism Pyrimidines - therapeutic use Receptor, Endothelin A Sulfonamides - therapeutic use Survival Rate Time |
| title | Long-term endothelin a receptor blockade inhibits electrical remodeling in cardiomyopathic hamsters |
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