A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs
The classical understanding of the mechanism of anti-anginal or anti-ischemic drugs is an increase in blood supply to the heart and/or a decrease in oxygen consumption of the heart, maintaining energy balance in the heart between supply and demand and hence maintaining the tissue levels of high-ener...
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| Veröffentlicht in: | Folia Pharmacologica Japonica 1996, Vol.108(4), pp.195-202 |
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| container_title | Folia Pharmacologica Japonica |
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| creator | ABIKO, Yasushi HASHIZUME, Hiroko HARA, Akiyoshi |
| description | The classical understanding of the mechanism of anti-anginal or anti-ischemic drugs is an increase in blood supply to the heart and/or a decrease in oxygen consumption of the heart, maintaining energy balance in the heart between supply and demand and hence maintaining the tissue levels of high-energy phosphates. This scheme is reasonable. During reperfusion following ischemia, however, there is more serious damage to the heart, although the tissue levels of highenergy phosphates increase. This is probably because toxic substances are generated in the heart during ischemia/reperfusion. We propose that both lysophosphatidylcholine and palmitoyl-L-carnitine that accumulate in the myocardium during ischemia/reperfusion are candidates for the toxic substances that accelerate ischemia/reperfusion damage to the heart. Therefore, drugs that have anti-lysophosphatidylcholine and/or anti-palmitoyl-L-carnitine effects are promising for the treatment of ischemic heart diseases. We found that K-7259, a novel derivative of dilazep having a minimal effect on the normal heart, is a drug that attenuates the deleterious effects of both lysophosphatidylcholine and palmitoyl-L-carnitine on the heart, and therefore attenuates the ischemia/reperfusion damage. |
| doi_str_mv | 10.1254/fpj.108.195 |
| format | Article |
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This scheme is reasonable. During reperfusion following ischemia, however, there is more serious damage to the heart, although the tissue levels of highenergy phosphates increase. This is probably because toxic substances are generated in the heart during ischemia/reperfusion. We propose that both lysophosphatidylcholine and palmitoyl-L-carnitine that accumulate in the myocardium during ischemia/reperfusion are candidates for the toxic substances that accelerate ischemia/reperfusion damage to the heart. Therefore, drugs that have anti-lysophosphatidylcholine and/or anti-palmitoyl-L-carnitine effects are promising for the treatment of ischemic heart diseases. We found that K-7259, a novel derivative of dilazep having a minimal effect on the normal heart, is a drug that attenuates the deleterious effects of both lysophosphatidylcholine and palmitoyl-L-carnitine on the heart, and therefore attenuates the ischemia/reperfusion damage.</description><identifier>ISSN: 0015-5691</identifier><identifier>EISSN: 1347-8397</identifier><identifier>DOI: 10.1254/fpj.108.195</identifier><identifier>PMID: 8940701</identifier><language>jpn</language><publisher>Japan: The Japanese Pharmacological Society</publisher><subject>Adrenergic beta-Antagonists - pharmacology ; Calcium Channel Blockers - pharmacology ; Coronary Circulation - drug effects ; Dilazep - analogs & derivatives ; Dilazep - pharmacology ; Diltiazem - pharmacology ; Energy Metabolism - drug effects ; Humans ; Lysophosphatidylcholines - metabolism ; Myocardial Ischemia - etiology ; Myocardial Ischemia - metabolism ; Myocardial Reperfusion Injury - etiology ; Myocardial Reperfusion Injury - metabolism ; Myocardium - metabolism ; Oxygen Consumption - drug effects ; Palmitoylcarnitine - metabolism ; Propranolol - pharmacology ; Vasodilator Agents - pharmacology</subject><ispartof>Folia Pharmacologica Japonica, 1996, Vol.108(4), pp.195-202</ispartof><rights>The Japanese PharmacologicalSociety</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3555-adba81fb5917a0e897aeadbce22ceb1570f89824f6075142e7c5e58f4f6ffc0d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,4025,27927,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8940701$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ABIKO, Yasushi</creatorcontrib><creatorcontrib>HASHIZUME, Hiroko</creatorcontrib><creatorcontrib>HARA, Akiyoshi</creatorcontrib><title>A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs</title><title>Folia Pharmacologica Japonica</title><addtitle>Nihon Yakurigaku Zasshi</addtitle><description>The classical understanding of the mechanism of anti-anginal or anti-ischemic drugs is an increase in blood supply to the heart and/or a decrease in oxygen consumption of the heart, maintaining energy balance in the heart between supply and demand and hence maintaining the tissue levels of high-energy phosphates. This scheme is reasonable. During reperfusion following ischemia, however, there is more serious damage to the heart, although the tissue levels of highenergy phosphates increase. This is probably because toxic substances are generated in the heart during ischemia/reperfusion. We propose that both lysophosphatidylcholine and palmitoyl-L-carnitine that accumulate in the myocardium during ischemia/reperfusion are candidates for the toxic substances that accelerate ischemia/reperfusion damage to the heart. Therefore, drugs that have anti-lysophosphatidylcholine and/or anti-palmitoyl-L-carnitine effects are promising for the treatment of ischemic heart diseases. We found that K-7259, a novel derivative of dilazep having a minimal effect on the normal heart, is a drug that attenuates the deleterious effects of both lysophosphatidylcholine and palmitoyl-L-carnitine on the heart, and therefore attenuates the ischemia/reperfusion damage.</description><subject>Adrenergic beta-Antagonists - pharmacology</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Coronary Circulation - drug effects</subject><subject>Dilazep - analogs & derivatives</subject><subject>Dilazep - pharmacology</subject><subject>Diltiazem - pharmacology</subject><subject>Energy Metabolism - drug effects</subject><subject>Humans</subject><subject>Lysophosphatidylcholines - metabolism</subject><subject>Myocardial Ischemia - etiology</subject><subject>Myocardial Ischemia - metabolism</subject><subject>Myocardial Reperfusion Injury - etiology</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Myocardium - metabolism</subject><subject>Oxygen Consumption - drug effects</subject><subject>Palmitoylcarnitine - metabolism</subject><subject>Propranolol - pharmacology</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0015-5691</issn><issn>1347-8397</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF9rwyAUxWVsdKXr054Hvo-0msSqj6XsHxT2sj0HY66NpTFBE8Y-wb72bFry4tVzjgfuD6FHSlY0ZfnadMcVJWJFJbtBc5rlPBGZ5LdoTghlCdtIeo-WIdiSEMZTvsnoDM2EzAkndI7-ttjBD1Zd51ula9y3uK8BD64CH3rlKusOuDWj2ICulbOhOQs26Boaq9YeOvBmCLZ1uFKNOgC2bszXoHyPY8f4AmNA9-H8V7neJtcCjSs_HMIDujPqFGB5nQv0_frytXtP9p9vH7vtPtEZYyxRVakENSWTlCsCQnIFUdOQphpKyjgxQoo0NxvCGc1T4JoBEyYKxmhSZQv0fOnVvg3Bgyk6bxvlfwtKijPQIgKNd1FEoDH9dEl3Q9lANWWv-KL_cvGPkdUBJj_ubfUJzl1U5vnYN52STX7k6Qtw2T-YdIwB</recordid><startdate>1996</startdate><enddate>1996</enddate><creator>ABIKO, Yasushi</creator><creator>HASHIZUME, Hiroko</creator><creator>HARA, Akiyoshi</creator><general>The Japanese Pharmacological Society</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></search><sort><creationdate>1996</creationdate><title>A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs</title><author>ABIKO, Yasushi ; HASHIZUME, Hiroko ; HARA, Akiyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3555-adba81fb5917a0e897aeadbce22ceb1570f89824f6075142e7c5e58f4f6ffc0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>jpn</language><creationdate>1996</creationdate><topic>Adrenergic beta-Antagonists - pharmacology</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Coronary Circulation - drug effects</topic><topic>Dilazep - analogs & derivatives</topic><topic>Dilazep - pharmacology</topic><topic>Diltiazem - pharmacology</topic><topic>Energy Metabolism - drug effects</topic><topic>Humans</topic><topic>Lysophosphatidylcholines - metabolism</topic><topic>Myocardial Ischemia - etiology</topic><topic>Myocardial Ischemia - metabolism</topic><topic>Myocardial Reperfusion Injury - etiology</topic><topic>Myocardial Reperfusion Injury - metabolism</topic><topic>Myocardium - metabolism</topic><topic>Oxygen Consumption - drug effects</topic><topic>Palmitoylcarnitine - metabolism</topic><topic>Propranolol - pharmacology</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ABIKO, Yasushi</creatorcontrib><creatorcontrib>HASHIZUME, Hiroko</creatorcontrib><creatorcontrib>HARA, Akiyoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Folia Pharmacologica Japonica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ABIKO, Yasushi</au><au>HASHIZUME, Hiroko</au><au>HARA, Akiyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs</atitle><jtitle>Folia Pharmacologica Japonica</jtitle><addtitle>Nihon Yakurigaku Zasshi</addtitle><date>1996</date><risdate>1996</risdate><volume>108</volume><issue>4</issue><spage>195</spage><epage>202</epage><pages>195-202</pages><issn>0015-5691</issn><eissn>1347-8397</eissn><abstract>The classical understanding of the mechanism of anti-anginal or anti-ischemic drugs is an increase in blood supply to the heart and/or a decrease in oxygen consumption of the heart, maintaining energy balance in the heart between supply and demand and hence maintaining the tissue levels of high-energy phosphates. This scheme is reasonable. During reperfusion following ischemia, however, there is more serious damage to the heart, although the tissue levels of highenergy phosphates increase. This is probably because toxic substances are generated in the heart during ischemia/reperfusion. We propose that both lysophosphatidylcholine and palmitoyl-L-carnitine that accumulate in the myocardium during ischemia/reperfusion are candidates for the toxic substances that accelerate ischemia/reperfusion damage to the heart. Therefore, drugs that have anti-lysophosphatidylcholine and/or anti-palmitoyl-L-carnitine effects are promising for the treatment of ischemic heart diseases. We found that K-7259, a novel derivative of dilazep having a minimal effect on the normal heart, is a drug that attenuates the deleterious effects of both lysophosphatidylcholine and palmitoyl-L-carnitine on the heart, and therefore attenuates the ischemia/reperfusion damage.</abstract><cop>Japan</cop><pub>The Japanese Pharmacological Society</pub><pmid>8940701</pmid><doi>10.1254/fpj.108.195</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0015-5691 |
| ispartof | Folia Pharmacologica Japonica, 1996, Vol.108(4), pp.195-202 |
| issn | 0015-5691 1347-8397 |
| language | jpn |
| recordid | cdi_crossref_primary_10_1254_fpj_108_195 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Adrenergic beta-Antagonists - pharmacology Calcium Channel Blockers - pharmacology Coronary Circulation - drug effects Dilazep - analogs & derivatives Dilazep - pharmacology Diltiazem - pharmacology Energy Metabolism - drug effects Humans Lysophosphatidylcholines - metabolism Myocardial Ischemia - etiology Myocardial Ischemia - metabolism Myocardial Reperfusion Injury - etiology Myocardial Reperfusion Injury - metabolism Myocardium - metabolism Oxygen Consumption - drug effects Palmitoylcarnitine - metabolism Propranolol - pharmacology Vasodilator Agents - pharmacology |
| title | A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs |
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