Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat
Objective: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion. Methods: Isolated rat hearts (n=10-l2 per group) were subjected to 30 min left regional ischaemia fo...
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| Veröffentlicht in: | Cardiovascular research 1993-03, Vol.27 (3), p.453-458 |
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| creator | Rees, Siân A Curtis, Michael J |
| description | Objective: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion. Methods: Isolated rat hearts (n=10-l2 per group) were subjected to 30 min left regional ischaemia followed by reperfusion with and without tacrine. Rat heart was used to permit delayed rectifier (IK) block to be disregarded in interpretation of results (rat ventricle is deficient in functional IK). Results: The incidence of ischaemia-induced ventricular fibrillation was reduced from 70% to 42%, 17% (p |
| doi_str_mv | 10.1093/cvr/27.3.453 |
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Methods: Isolated rat hearts (n=10-l2 per group) were subjected to 30 min left regional ischaemia followed by reperfusion with and without tacrine. Rat heart was used to permit delayed rectifier (IK) block to be disregarded in interpretation of results (rat ventricle is deficient in functional IK). Results: The incidence of ischaemia-induced ventricular fibrillation was reduced from 70% to 42%, 17% (p<0.05), and 0% (p<0.05) in hearts perfused with 0, 0.1, 1.0, and 10.0 μM tacrine. Likewise, the incidence of reperfusion induced ventricular fibrillation was reduced from 100% to 90%, 75%, and 50% (p<0.05), respectively. Indirect evidence of repolarisation delay by tacrine was provided by QT widening; for example, 15 min after the onset of ischaemia, QT (at 100% repolarisation) was increased from 194(SEM 6) to 231(17), 235(13) (p<0.05), and 341(24) ms (p<0.05) by increasing concentrations of drug. QT interval measured in individual hearts during ischaemia correlated inversely with arrhythmia score (r2=0.392; p<0.001). Tacrine had no effect on RR interval, coronary flow, recovery of flow during reperfusion, or occluded zone size. Tacrine caused bradycardia (significant at the 1.0 and 10.0 μM concentrations). In additional hearts (n=12 per group), reversal of 10.0 μM tacrine-induced sinus bradycardia by left atrial pacing (5 Hz) significantly reduced tacrine induced QT widening (p<0.05), and increased the incidence of ventricular fibrillation from 0% to 42% (although significant antiarrhythmic and QT widening effects were still present); 10.0 (μM tacrine failed to reduce the incidence of reperfusion induced ventricular fibrillation in paced hearts (92% incidence v 100% in controls). Conclusions: The novel antiarrhythmic effects of tacrine, a drug with established blocking action on IK, IK1, and slow inward current, appear to result from QT widening in the rat (dependent partly on IK1 blockade in the ventricles and partly on drug induced sinus bradycardia). Cardiovascular Research 1993;27:453-458]]></description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/27.3.453</identifier><identifier>PMID: 8490946</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Antiarythmic agents ; Biological and medical sciences ; Cardiac Pacing, Artificial ; Cardiovascular system ; Coronary Circulation - drug effects ; Dose-Response Relationship, Drug ; Electrocardiography ; Heart Rate - drug effects ; IK1 ; Male ; Medical sciences ; myocardial ischaemia ; Myocardial Ischemia - complications ; Myocardial Reperfusion ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; reperfusion ; tacrine ; Tacrine - pharmacology ; ventricular fibrillation ; Ventricular Fibrillation - prevention & control</subject><ispartof>Cardiovascular research, 1993-03, Vol.27 (3), p.453-458</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c338t-cc69d54da4b7b583236c88c9472fb894c57009ea2684b73c25cc8a07b94cd4d73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4724881$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8490946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rees, Siân A</creatorcontrib><creatorcontrib>Curtis, Michael J</creatorcontrib><title>Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description><![CDATA[Objective: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion. Methods: Isolated rat hearts (n=10-l2 per group) were subjected to 30 min left regional ischaemia followed by reperfusion with and without tacrine. Rat heart was used to permit delayed rectifier (IK) block to be disregarded in interpretation of results (rat ventricle is deficient in functional IK). Results: The incidence of ischaemia-induced ventricular fibrillation was reduced from 70% to 42%, 17% (p<0.05), and 0% (p<0.05) in hearts perfused with 0, 0.1, 1.0, and 10.0 μM tacrine. Likewise, the incidence of reperfusion induced ventricular fibrillation was reduced from 100% to 90%, 75%, and 50% (p<0.05), respectively. Indirect evidence of repolarisation delay by tacrine was provided by QT widening; for example, 15 min after the onset of ischaemia, QT (at 100% repolarisation) was increased from 194(SEM 6) to 231(17), 235(13) (p<0.05), and 341(24) ms (p<0.05) by increasing concentrations of drug. QT interval measured in individual hearts during ischaemia correlated inversely with arrhythmia score (r2=0.392; p<0.001). Tacrine had no effect on RR interval, coronary flow, recovery of flow during reperfusion, or occluded zone size. Tacrine caused bradycardia (significant at the 1.0 and 10.0 μM concentrations). In additional hearts (n=12 per group), reversal of 10.0 μM tacrine-induced sinus bradycardia by left atrial pacing (5 Hz) significantly reduced tacrine induced QT widening (p<0.05), and increased the incidence of ventricular fibrillation from 0% to 42% (although significant antiarrhythmic and QT widening effects were still present); 10.0 (μM tacrine failed to reduce the incidence of reperfusion induced ventricular fibrillation in paced hearts (92% incidence v 100% in controls). Conclusions: The novel antiarrhythmic effects of tacrine, a drug with established blocking action on IK, IK1, and slow inward current, appear to result from QT widening in the rat (dependent partly on IK1 blockade in the ventricles and partly on drug induced sinus bradycardia). Cardiovascular Research 1993;27:453-458]]></description><subject>Animals</subject><subject>Antiarythmic agents</subject><subject>Biological and medical sciences</subject><subject>Cardiac Pacing, Artificial</subject><subject>Cardiovascular system</subject><subject>Coronary Circulation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrocardiography</subject><subject>Heart Rate - drug effects</subject><subject>IK1</subject><subject>Male</subject><subject>Medical sciences</subject><subject>myocardial ischaemia</subject><subject>Myocardial Ischemia - complications</subject><subject>Myocardial Reperfusion</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>reperfusion</subject><subject>tacrine</subject><subject>Tacrine - pharmacology</subject><subject>ventricular fibrillation</subject><subject>Ventricular Fibrillation - prevention & control</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1rGzEQxUVpSZ2PW68FHUpPWUe7I620x2KapJBQAg6EXMTsSEvUrteutOsm_31kbHyaGd5vhjePsS-lmJeigSvaxqtKz2EuFXxgs1IrVUAl1Uc2E0KYooYaPrPTlP7kUSktT9iJkY1oZD1j_RIphsHzMLyENoyJb_0wxkBTj5F3oY2h73EM6yETbiLvePvGQ6IX9KuAHAfHo9_42E1pB-3m_8H5IfGHZV4ZfdxinxsecTxnnzrsk7841DP2eP1zubgt7n7f_Fr8uCsIwIwFUd04JR3KVrfKQAU1GUON1FXXmkaS0kI0HqvaZAKoUkQGhW6z5KTTcMa-7-9u4vrf5NNoV9mxz48Mfj0lq5UGpWAHXu5BiuuUou_sJoYVxjdbCrsL1-ZwbaUt2Bxuxr8e7k7tyrsjfEgz698OOibCvos4UEhHLPuXxpQZK_ZYSKN_PcoY_9pag1b29unZ3i-umwWYB3sP7xv6krU</recordid><startdate>199303</startdate><enddate>199303</enddate><creator>Rees, Siân A</creator><creator>Curtis, Michael J</creator><general>Oxford University Press</general><scope>BSCLL</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>199303</creationdate><title>Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat</title><author>Rees, Siân A ; Curtis, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c338t-cc69d54da4b7b583236c88c9472fb894c57009ea2684b73c25cc8a07b94cd4d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Animals</topic><topic>Antiarythmic agents</topic><topic>Biological and medical sciences</topic><topic>Cardiac Pacing, Artificial</topic><topic>Cardiovascular system</topic><topic>Coronary Circulation - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrocardiography</topic><topic>Heart Rate - drug effects</topic><topic>IK1</topic><topic>Male</topic><topic>Medical sciences</topic><topic>myocardial ischaemia</topic><topic>Myocardial Ischemia - complications</topic><topic>Myocardial Reperfusion</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>reperfusion</topic><topic>tacrine</topic><topic>Tacrine - pharmacology</topic><topic>ventricular fibrillation</topic><topic>Ventricular Fibrillation - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rees, Siân A</creatorcontrib><creatorcontrib>Curtis, Michael J</creatorcontrib><collection>Istex</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>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rees, Siân A</au><au>Curtis, Michael J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>1993-03</date><risdate>1993</risdate><volume>27</volume><issue>3</issue><spage>453</spage><epage>458</epage><pages>453-458</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract><![CDATA[Objective: Tacrine was used as a tool to examine whether block of inward rectifying potassium current (IK1) represents a mechanism for suppression of arrhythmias induced by ischaemia and reperfusion. Methods: Isolated rat hearts (n=10-l2 per group) were subjected to 30 min left regional ischaemia followed by reperfusion with and without tacrine. Rat heart was used to permit delayed rectifier (IK) block to be disregarded in interpretation of results (rat ventricle is deficient in functional IK). Results: The incidence of ischaemia-induced ventricular fibrillation was reduced from 70% to 42%, 17% (p<0.05), and 0% (p<0.05) in hearts perfused with 0, 0.1, 1.0, and 10.0 μM tacrine. Likewise, the incidence of reperfusion induced ventricular fibrillation was reduced from 100% to 90%, 75%, and 50% (p<0.05), respectively. Indirect evidence of repolarisation delay by tacrine was provided by QT widening; for example, 15 min after the onset of ischaemia, QT (at 100% repolarisation) was increased from 194(SEM 6) to 231(17), 235(13) (p<0.05), and 341(24) ms (p<0.05) by increasing concentrations of drug. QT interval measured in individual hearts during ischaemia correlated inversely with arrhythmia score (r2=0.392; p<0.001). Tacrine had no effect on RR interval, coronary flow, recovery of flow during reperfusion, or occluded zone size. Tacrine caused bradycardia (significant at the 1.0 and 10.0 μM concentrations). In additional hearts (n=12 per group), reversal of 10.0 μM tacrine-induced sinus bradycardia by left atrial pacing (5 Hz) significantly reduced tacrine induced QT widening (p<0.05), and increased the incidence of ventricular fibrillation from 0% to 42% (although significant antiarrhythmic and QT widening effects were still present); 10.0 (μM tacrine failed to reduce the incidence of reperfusion induced ventricular fibrillation in paced hearts (92% incidence v 100% in controls). Conclusions: The novel antiarrhythmic effects of tacrine, a drug with established blocking action on IK, IK1, and slow inward current, appear to result from QT widening in the rat (dependent partly on IK1 blockade in the ventricles and partly on drug induced sinus bradycardia). Cardiovascular Research 1993;27:453-458]]></abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>8490946</pmid><doi>10.1093/cvr/27.3.453</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Antiarythmic agents Biological and medical sciences Cardiac Pacing, Artificial Cardiovascular system Coronary Circulation - drug effects Dose-Response Relationship, Drug Electrocardiography Heart Rate - drug effects IK1 Male Medical sciences myocardial ischaemia Myocardial Ischemia - complications Myocardial Reperfusion Pharmacology. Drug treatments Rats Rats, Wistar reperfusion tacrine Tacrine - pharmacology ventricular fibrillation Ventricular Fibrillation - prevention & control |
| title | Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat |
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