Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs
Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion in...
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| Veröffentlicht in: | European journal of pharmacology 2004-11, Vol.505 (1-3), p.163-168 |
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| container_title | European journal of pharmacology |
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| creator | TAKAHASHI, Teisuke TAKAHASHI, Kenzo ONISHI, Michihito SUZUKI, Taizo TANAKA, Yu OTA, Tomomi YOSHIDA, Shigeru NAKAIKE, Shiro MATSUDA, Toshio BABA, Akemichi |
| description | Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of the left anterior descending coronary artery followed by a 4-h reperfusion in anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent segment shortening but remained depressed during a 4-h reperfusion period. A bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before reperfusion, improved significantly the recovery of percent segment shortening in the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion-induced change in coronary blood flow. These results suggest that the Na+/Ca2+ exchanger is involved in the stunned myocardium of dogs after reperfusion, and that SEA0400 has a protective effect against myocardial stunning in dogs. |
| doi_str_mv | 10.1016/j.ejphar.2004.10.030 |
| format | Article |
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We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of the left anterior descending coronary artery followed by a 4-h reperfusion in anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent segment shortening but remained depressed during a 4-h reperfusion period. A bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before reperfusion, improved significantly the recovery of percent segment shortening in the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion-induced change in coronary blood flow. These results suggest that the Na+/Ca2+ exchanger is involved in the stunned myocardium of dogs after reperfusion, and that SEA0400 has a protective effect against myocardial stunning in dogs.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2004.10.030</identifier><identifier>PMID: 15556149</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier</publisher><subject>Anesthesia ; Aniline Compounds - pharmacology ; Animals ; Biological and medical sciences ; Blood Pressure - drug effects ; Dogs ; Female ; Heart - drug effects ; Heart - physiopathology ; Heart Rate - drug effects ; Male ; Medical sciences ; Myocardial Reperfusion Injury - complications ; Myocardial Stunning - etiology ; Myocardial Stunning - physiopathology ; Myocardial Stunning - prevention & control ; Pharmacology. Drug treatments ; Phenyl Ethers - pharmacology ; Random Allocation ; Sodium-Calcium Exchanger - antagonists & inhibitors ; Time Factors</subject><ispartof>European journal of pharmacology, 2004-11, Vol.505 (1-3), p.163-168</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-e9fbcbb4112eba023a05acd550219918d401c9f600baa3ed5f546ee0fd4be9b93</citedby><cites>FETCH-LOGICAL-c331t-e9fbcbb4112eba023a05acd550219918d401c9f600baa3ed5f546ee0fd4be9b93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16291378$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15556149$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TAKAHASHI, Teisuke</creatorcontrib><creatorcontrib>TAKAHASHI, Kenzo</creatorcontrib><creatorcontrib>ONISHI, Michihito</creatorcontrib><creatorcontrib>SUZUKI, Taizo</creatorcontrib><creatorcontrib>TANAKA, Yu</creatorcontrib><creatorcontrib>OTA, Tomomi</creatorcontrib><creatorcontrib>YOSHIDA, Shigeru</creatorcontrib><creatorcontrib>NAKAIKE, Shiro</creatorcontrib><creatorcontrib>MATSUDA, Toshio</creatorcontrib><creatorcontrib>BABA, Akemichi</creatorcontrib><title>Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of the left anterior descending coronary artery followed by a 4-h reperfusion in anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent segment shortening but remained depressed during a 4-h reperfusion period. A bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before reperfusion, improved significantly the recovery of percent segment shortening in the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion-induced change in coronary blood flow. These results suggest that the Na+/Ca2+ exchanger is involved in the stunned myocardium of dogs after reperfusion, and that SEA0400 has a protective effect against myocardial stunning in dogs.</description><subject>Anesthesia</subject><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Dogs</subject><subject>Female</subject><subject>Heart - drug effects</subject><subject>Heart - physiopathology</subject><subject>Heart Rate - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Myocardial Reperfusion Injury - complications</subject><subject>Myocardial Stunning - etiology</subject><subject>Myocardial Stunning - physiopathology</subject><subject>Myocardial Stunning - prevention & control</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenyl Ethers - pharmacology</subject><subject>Random Allocation</subject><subject>Sodium-Calcium Exchanger - antagonists & inhibitors</subject><subject>Time Factors</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1vEzEQhi0EoqHwDxDyBS7tpmOvvYmPVRQ-pAoOwHk19o4TRxs72BvU8utxlEg9jfTO845GD2PvBcwFiO5uN6fdYYt5LgFUjebQwgs2E8uFaWAh5Es2AxCqkcaYK_amlB0AaCP1a3YltNadUGbGxrX35KbCk-c_1_egAG458pj-0shD3AYbppRP22lL_Dve3K1Q3nB6dFuMG8q3PEW-f0oO8xBw5GU6xhjipnY5Riq1NYV_NPAhbcpb9srjWOjdZV6z35_Xv1Zfm4cfX76t7h8a17Ziash466xVQkiyCLJF0OgGrUEKY8RyUCCc8R2ARWxp0F6rjgj8oCwZa9pr9ul895DTn2N9ot-H4mgc60fpWPpuAUYulaqgOoMup1Iy-f6Qwx7zUy-gP1nud_3Zcn-yfEqr5Vr7cLl_tHsanksXrRX4eAGwOBx9xuhCeeY6aUS7WLb_AdZPhsc</recordid><startdate>20041128</startdate><enddate>20041128</enddate><creator>TAKAHASHI, Teisuke</creator><creator>TAKAHASHI, Kenzo</creator><creator>ONISHI, Michihito</creator><creator>SUZUKI, Taizo</creator><creator>TANAKA, Yu</creator><creator>OTA, Tomomi</creator><creator>YOSHIDA, Shigeru</creator><creator>NAKAIKE, Shiro</creator><creator>MATSUDA, Toshio</creator><creator>BABA, Akemichi</creator><general>Elsevier</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>20041128</creationdate><title>Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs</title><author>TAKAHASHI, Teisuke ; TAKAHASHI, Kenzo ; ONISHI, Michihito ; SUZUKI, Taizo ; TANAKA, Yu ; OTA, Tomomi ; YOSHIDA, Shigeru ; NAKAIKE, Shiro ; MATSUDA, Toshio ; BABA, Akemichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-e9fbcbb4112eba023a05acd550219918d401c9f600baa3ed5f546ee0fd4be9b93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Anesthesia</topic><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Dogs</topic><topic>Female</topic><topic>Heart - drug effects</topic><topic>Heart - physiopathology</topic><topic>Heart Rate - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Myocardial Reperfusion Injury - complications</topic><topic>Myocardial Stunning - etiology</topic><topic>Myocardial Stunning - physiopathology</topic><topic>Myocardial Stunning - prevention & control</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenyl Ethers - pharmacology</topic><topic>Random Allocation</topic><topic>Sodium-Calcium Exchanger - antagonists & inhibitors</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TAKAHASHI, Teisuke</creatorcontrib><creatorcontrib>TAKAHASHI, Kenzo</creatorcontrib><creatorcontrib>ONISHI, Michihito</creatorcontrib><creatorcontrib>SUZUKI, Taizo</creatorcontrib><creatorcontrib>TANAKA, Yu</creatorcontrib><creatorcontrib>OTA, Tomomi</creatorcontrib><creatorcontrib>YOSHIDA, Shigeru</creatorcontrib><creatorcontrib>NAKAIKE, Shiro</creatorcontrib><creatorcontrib>MATSUDA, Toshio</creatorcontrib><creatorcontrib>BABA, Akemichi</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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TAKAHASHI, Teisuke</au><au>TAKAHASHI, Kenzo</au><au>ONISHI, Michihito</au><au>SUZUKI, Taizo</au><au>TANAKA, Yu</au><au>OTA, Tomomi</au><au>YOSHIDA, Shigeru</au><au>NAKAIKE, Shiro</au><au>MATSUDA, Toshio</au><au>BABA, Akemichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2004-11-28</date><risdate>2004</risdate><volume>505</volume><issue>1-3</issue><spage>163</spage><epage>168</epage><pages>163-168</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Activation of the Na+/Ca2+ exchanger may contribute to Ca2+ overload during reperfusion after transient ischemia. We examined the effects of 2-[4-[(2,5-difluorophenyl) methoxy]phenoxy]-5-ethoxyaniline (SEA0400), a selective inhibitor of Na+/Ca2+ exchange, on a canine model of ischemia/reperfusion injury (myocardial stunning). Myocardial stunning was induced by a 15-min occlusion of the left anterior descending coronary artery followed by a 4-h reperfusion in anesthetized open-chest dogs. Reperfusion gradually restored myocardial percent segment shortening but remained depressed during a 4-h reperfusion period. A bolus intravenous injection of SEA0400 (0.3 or 1.0 mg/kg), given 1 min before reperfusion, improved significantly the recovery of percent segment shortening in the ischemic/reperfused myocardium. SEA0400 did not affect the hemodynamics and electrocardiogram parameters. In addition, SEA0400 did not affect reperfusion-induced change in coronary blood flow. These results suggest that the Na+/Ca2+ exchanger is involved in the stunned myocardium of dogs after reperfusion, and that SEA0400 has a protective effect against myocardial stunning in dogs.</abstract><cop>Amsterdam</cop><pub>Elsevier</pub><pmid>15556149</pmid><doi>10.1016/j.ejphar.2004.10.030</doi><tpages>6</tpages></addata></record> |
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| subjects | Anesthesia Aniline Compounds - pharmacology Animals Biological and medical sciences Blood Pressure - drug effects Dogs Female Heart - drug effects Heart - physiopathology Heart Rate - drug effects Male Medical sciences Myocardial Reperfusion Injury - complications Myocardial Stunning - etiology Myocardial Stunning - physiopathology Myocardial Stunning - prevention & control Pharmacology. Drug treatments Phenyl Ethers - pharmacology Random Allocation Sodium-Calcium Exchanger - antagonists & inhibitors Time Factors |
| title | Effects of SEA0400, a novel inhibitor of the Na+/Ca2+ exchanger, on myocardial stunning in anesthetized dogs |
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