Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts
Identifieur interne : 001A31 ( Istex/Corpus ); précédent : 001A30; suivant : 001A32Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts
Auteurs : Nisar A. ShaikhSource :
- Journal of Molecular and Cellular Cardiology [ 0022-2828 ] ; 1992.
English descriptors
- Teeft :
- 1ysopl, 1ysopl levels, Acute ischaemia, Acyl, Alkenyl species, Amiodarone, Amiodarone therapy, Amiodarone treatment, Amphiphilic lipids, Ample evidence, Antiarrhythmic, Antiarrhythmic agent, Attenuated, Bacterial phospholipase, Beneficial effects, Biochem biophys, Biol chem, Biopsy, Cardiac ischemia, Cardiol, Cell biochem, Cell cardiol, Chronic treatment, Circ, Coronary artery occlusion, Different compartments, Different periods, Downar, Early phase, Electrophysiological, Electrophysiological properties, Endogenous drug, Entire time course, Fatty acid, Fatty acid levels, Fatty acids, Further work, Global ischaemia, Haemodynamic effects, Heart homogenates, Heart model, Heart preparations, Hydrolysis, Infarct size, Intact heart biopsies, Internal standards, Irreversible phase, Ischaemia, Ischaemia model, Ischaemic, Ischaemic heart, Ischaemic injury, Ischaemic insult, Ischemia, Ischemic, Latter study, Lipid, Lipid amphiphiles, Lysophospholipid, Lysophospholipid accumulation, Lysosomal, Lysosomal enzymes, Lysosomal phospholipases, Lysosome, Membrane, Membrane bilayer, Membrane dysfunction, Membrane integrity, Membrane phospholipids, Molecular species, More hours, Myocardial, Myocardial ischaemia, Myocardial phospholipid hydrolysis, Myocardium, Nefa, Nefa levels, Occlusion, Organelle, Other compartments, Other enzymes, Other subcellular organelles, Percentage increase, Percentage losses, Perfused retrogradely, Phospholipase, Phospholipase activities, Phospholipase inhibition, Phospholipases, Phospholipid, Phospholipid classes, Phospholipidosis, Porcine heart, Previous studies, Protective effects, Sequential lysosomal alterations, Shaikh, Significant attenuation, Significant losses, Significant significance, Snake venom phospholipase, Subcellular, Time course, Time increase accumulation, Tissue levels, Total ischaemia, Total ischaemia model, Total ischemia, Total phospholipid, Total phospholipids, Ultrastructural changes, Untreated, Untreated animals, Untreated groups, Untreated hearts, Various enzyme activities, Various periods, Various time intervals, Ventricular, Ventricular arrhythmias, Ventricular fibrillation, Water content.
Abstract
Abstract: The effects of chronic amiodarone therpy oon myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 ± 13 & 122 ± 22 μm (n = 12) for amiodarone and its principle metabolite, desethylamiodamine, respectively. This was accompanied by a significant increase (37%, P<0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosommes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.
Url:
DOI: 10.1016/0022-2828(92)91840-2
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ISTEX:0F1479CA463F91A1600360B7A7C0731E37661866Le document en format XML
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Shaikh</name><affiliation><mods:affiliation>Department of Medicine, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Molecular and Cellular Cardiology</title><title level="j" type="abbrev">YJMCC</title><idno type="ISSN">0022-2828</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1992">1992</date><biblScope unit="volume">24</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="507">507</biblScope><biblScope unit="page" to="521">521</biblScope></imprint><idno type="ISSN">0022-2828</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2828</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>1ysopl</term><term>1ysopl levels</term><term>Acute ischaemia</term><term>Acyl</term><term>Alkenyl species</term><term>Amiodarone</term><term>Amiodarone therapy</term><term>Amiodarone treatment</term><term>Amphiphilic lipids</term><term>Ample evidence</term><term>Antiarrhythmic</term><term>Antiarrhythmic agent</term><term>Attenuated</term><term>Bacterial phospholipase</term><term>Beneficial effects</term><term>Biochem biophys</term><term>Biol chem</term><term>Biopsy</term><term>Cardiac ischemia</term><term>Cardiol</term><term>Cell biochem</term><term>Cell cardiol</term><term>Chronic treatment</term><term>Circ</term><term>Coronary artery occlusion</term><term>Different compartments</term><term>Different periods</term><term>Downar</term><term>Early phase</term><term>Electrophysiological</term><term>Electrophysiological properties</term><term>Endogenous drug</term><term>Entire time course</term><term>Fatty acid</term><term>Fatty acid levels</term><term>Fatty acids</term><term>Further work</term><term>Global ischaemia</term><term>Haemodynamic effects</term><term>Heart homogenates</term><term>Heart model</term><term>Heart preparations</term><term>Hydrolysis</term><term>Infarct size</term><term>Intact heart biopsies</term><term>Internal standards</term><term>Irreversible phase</term><term>Ischaemia</term><term>Ischaemia model</term><term>Ischaemic</term><term>Ischaemic heart</term><term>Ischaemic injury</term><term>Ischaemic insult</term><term>Ischemia</term><term>Ischemic</term><term>Latter study</term><term>Lipid</term><term>Lipid amphiphiles</term><term>Lysophospholipid</term><term>Lysophospholipid accumulation</term><term>Lysosomal</term><term>Lysosomal enzymes</term><term>Lysosomal phospholipases</term><term>Lysosome</term><term>Membrane</term><term>Membrane bilayer</term><term>Membrane dysfunction</term><term>Membrane integrity</term><term>Membrane phospholipids</term><term>Molecular species</term><term>More hours</term><term>Myocardial</term><term>Myocardial ischaemia</term><term>Myocardial phospholipid hydrolysis</term><term>Myocardium</term><term>Nefa</term><term>Nefa levels</term><term>Occlusion</term><term>Organelle</term><term>Other compartments</term><term>Other enzymes</term><term>Other subcellular organelles</term><term>Percentage increase</term><term>Percentage losses</term><term>Perfused retrogradely</term><term>Phospholipase</term><term>Phospholipase activities</term><term>Phospholipase inhibition</term><term>Phospholipases</term><term>Phospholipid</term><term>Phospholipid classes</term><term>Phospholipidosis</term><term>Porcine heart</term><term>Previous studies</term><term>Protective effects</term><term>Sequential lysosomal alterations</term><term>Shaikh</term><term>Significant attenuation</term><term>Significant losses</term><term>Significant significance</term><term>Snake venom phospholipase</term><term>Subcellular</term><term>Time course</term><term>Time increase accumulation</term><term>Tissue levels</term><term>Total ischaemia</term><term>Total ischaemia model</term><term>Total ischemia</term><term>Total phospholipid</term><term>Total phospholipids</term><term>Ultrastructural changes</term><term>Untreated</term><term>Untreated animals</term><term>Untreated groups</term><term>Untreated hearts</term><term>Various enzyme activities</term><term>Various periods</term><term>Various time intervals</term><term>Ventricular</term><term>Ventricular arrhythmias</term><term>Ventricular fibrillation</term><term>Water content</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The effects of chronic amiodarone therpy oon myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 ± 13 & 122 ± 22 μm (n = 12) for amiodarone and its principle metabolite, desethylamiodamine, respectively. This was accompanied by a significant increase (37%, P<0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosommes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>ischaemia</json:string><json:string>amiodarone</json:string><json:string>phospholipid</json:string><json:string>phospholipase</json:string><json:string>lipid</json:string><json:string>ischaemic</json:string><json:string>shaikh</json:string><json:string>untreated</json:string><json:string>untreated 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levels</json:string><json:string>other subcellular organelles</json:string><json:string>global ischaemia</json:string><json:string>infarct size</json:string><json:string>membrane dysfunction</json:string><json:string>nefa levels</json:string><json:string>acute ischaemia</json:string><json:string>porcine heart</json:string><json:string>membrane phospholipids</json:string><json:string>cell biochem</json:string><json:string>untreated groups</json:string><json:string>hydrolysis</json:string><json:string>myocardial</json:string><json:string>snake venom phospholipase</json:string><json:string>percentage losses</json:string><json:string>significant significance</json:string><json:string>bacterial phospholipase</json:string><json:string>phospholipid classes</json:string><json:string>electrophysiological properties</json:string><json:string>ample evidence</json:string><json:string>myocardial phospholipid hydrolysis</json:string><json:string>coronary artery 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intervals</json:string></teeft></keywords><author><json:item><name>Nisar A. Shaikh</name><affiliations><json:string>Department of Medicine, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Amiodarone therapy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>in vitro total ischaemia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Isolated perfused heart</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Time-course of phospholipid hydrolysis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Lysophospholipid accumulation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Fatty acid release</value></json:item></subject><arkIstex>ark:/67375/6H6-CC8GJMVS-4</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>Abstract: The effects of chronic amiodarone therpy oon myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 ± 13 & 122 ± 22 μm (n = 12) for amiodarone and its principle metabolite, desethylamiodamine, respectively. This was accompanied by a significant increase (37%, P>0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosommes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.</abstract><qualityIndicators><score>10</score><pdfWordCount>5292</pdfWordCount><pdfCharCount>43641</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>15</pdfPageCount><pdfPageSize>475.68 x 719.84 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>343</abstractWordCount><abstractCharCount>2365</abstractCharCount><keywordCount>6</keywordCount></qualityIndicators><title>Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts</title><pmid><json:string>1635074</json:string></pmid><pii><json:string>0022-2828(92)91840-2</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>Journal of Molecular and Cellular Cardiology</title><language><json:string>unknown</json:string></language><publicationDate>1992</publicationDate><issn><json:string>0022-2828</json:string></issn><pii><json:string>S0022-2828(00)X0212-X</json:string></pii><volume>24</volume><issue>5</issue><pages><first>507</first><last>521</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1992</json:string></date><geogName></geogName><orgName><json:string>Canada of Toronto, Room</json:string><json:string>Stroke Foundation of Ontario</json:string><json:string>Canadian Heart Foundation Scholar</json:string><json:string>Sigma Chemical Co.</json:string><json:string>Heart</json:string><json:string>Medical Research Council of Canada</json:string></orgName><orgName_funder><json:string>Heart</json:string><json:string>Medical Research Council of Canada</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Molly Pind</json:string><json:string>A. 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Shaikh</json:string><json:string>O.Ol</json:string></persName><placeName><json:string>Canada</json:string><json:string>Toronto</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>[34]</json:string><json:string>[29]</json:string><json:string>[55]</json:string><json:string>[8]</json:string><json:string>[38]</json:string><json:string>[3]</json:string><json:string>[42]</json:string><json:string>[5]</json:string><json:string>[26]</json:string><json:string>[14]</json:string><json:string>[40]</json:string><json:string>[24]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-CC8GJMVS-4</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - cell biology</json:string><json:string>2 - cardiac & cardiovascular systems</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - cardiovascular system & hematology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Cardiology and Cardiovascular Medicine</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Molecular Biology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1992</publicationDate><copyrightDate>1992</copyrightDate><doi><json:string>10.1016/0022-2828(92)91840-2</json:string></doi><id>0F1479CA463F91A1600360B7A7C0731E37661866</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-CC8GJMVS-4/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-CC8GJMVS-4/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-CC8GJMVS-4/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a">Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>elsevier</p></licence></availability><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M"></p><date>1992</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Section title: Original article</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts</title><author xml:id="author-0000"><persName><forename type="first">Nisar A.</forename><surname>Shaikh</surname></persName><affiliation>Please address all correspondence to: Nisar A. Shaikh, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ont., Canada M5S 1A8.</affiliation><affiliation>Department of Medicine, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</affiliation></author><idno type="istex">0F1479CA463F91A1600360B7A7C0731E37661866</idno><idno type="ark">ark:/67375/6H6-CC8GJMVS-4</idno><idno type="DOI">10.1016/0022-2828(92)91840-2</idno><idno type="PII">0022-2828(92)91840-2</idno></analytic><monogr><title level="j">Journal of Molecular and Cellular Cardiology</title><title level="j" type="abbrev">YJMCC</title><idno type="pISSN">0022-2828</idno><idno type="PII">S0022-2828(00)X0212-X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1992"></date><biblScope unit="volume">24</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="507">507</biblScope><biblScope unit="page" to="521">521</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1992</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The effects of chronic amiodarone therpy oon myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 ± 13 & 122 ± 22 μm (n = 12) for amiodarone and its principle metabolite, desethylamiodamine, respectively. This was accompanied by a significant increase (37%, P<0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosommes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Amiodarone therapy</term></item><item><term>in vitro total ischaemia</term></item><item><term>Isolated perfused heart</term></item><item><term>Time-course of phospholipid hydrolysis</term></item><item><term>Lysophospholipid accumulation</term></item><item><term>Fatty acid release</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1992">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-CC8GJMVS-4/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>YJMCC</jid><aid>92918402</aid><ce:pii>0022-2828(92)91840-2</ce:pii><ce:doi>10.1016/0022-2828(92)91840-2</ce:doi><ce:copyright type="unknown" year="1992"></ce:copyright></item-info><head><ce:dochead><ce:textfn>Original article</ce:textfn></ce:dochead><ce:title>Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during <ce:italic>in vitro</ce:italic> total ischaemia in cat hearts</ce:title><ce:author-group><ce:author><ce:given-name>Nisar A.</ce:given-name><ce:surname>Shaikh</ce:surname><ce:cross-ref refid="COR1"><ce:sup>∗</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Medicine, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Department of Clinical Biochemistry, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Centre for Cardiovascular Research, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>∗</ce:label><ce:text>Please address all correspondence to: Nisar A. Shaikh, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ont., Canada M5S 1A8.</ce:text></ce:correspondence></ce:author-group><ce:date-received day="26" month="2" year="1990"></ce:date-received><ce:date-accepted day="18" month="12" year="1991"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>The effects of chronic amiodarone therpy oon myocardial phospholipid hydrolysis induced by total <ce:italic>in vitro</ce:italic> ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 ± 13 & 122 ± 22 μ<ce:small-caps>m</ce:small-caps> (<ce:italic>n</ce:italic> = 12) for amiodarone and its principle metabolite, desethylamiodamine, respectively. This was accompanied by a significant increase (37%, <ce:italic>P</ce:italic><0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon <ce:italic>in vitro</ce:italic> total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an <ce:italic>in vitro</ce:italic> total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosommes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Amiodarone therapy</ce:text></ce:keyword><ce:keyword><ce:text><ce:italic>in vitro</ce:italic> total ischaemia</ce:text></ce:keyword><ce:keyword><ce:text>Isolated perfused heart</ce:text></ce:keyword><ce:keyword><ce:text>Time-course of phospholipid hydrolysis</ce:text></ce:keyword><ce:keyword><ce:text>Lysophospholipid accumulation</ce:text></ce:keyword><ce:keyword><ce:text>Fatty acid release</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during in vitro total ischaemia in cat hearts</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Effect of amiodarone therapy on the time course of myocardial phospholipid hydrolysis during</title></titleInfo><name type="personal"><namePart type="given">Nisar A.</namePart><namePart type="family">Shaikh</namePart><affiliation>Department of Medicine, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8</affiliation><description>Please address all correspondence to: Nisar A. Shaikh, University of Toronto, Room 7358, Medical Sciences Building, 1 King's College Circle, Toronto, Ont., Canada M5S 1A8.</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1992</dateIssued><copyrightDate encoding="w3cdtf">1992</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The effects of chronic amiodarone therpy oon myocardial phospholipid hydrolysis induced by total in vitro ischaemia were investigated in cat hearts. Chronic treatment of cats with amiodarone (30 mg/kg/day, orally) for 6 weeks resulted in a sufficient uptake of the drug reaching tissue levels of 83 ± 13 & 122 ± 22 μm (n = 12) for amiodarone and its principle metabolite, desethylamiodamine, respectively. This was accompanied by a significant increase (37%, P<0.001) in total phospholipid content of heart in treated as compared to untreated animals. Upon in vitro total ischaemia, these endogenous drug levels were sufficient to attenuate significantly hydrolysis of membrane phospholipid. The degree of attenuation was dependent upon the duration of ischaemic insult. In this regard, protection against phospholipid losses by amiodarone treatment was significantly more in the later irreversible phase of ischaemic injury whether studied in an in vitro total ischaemia model or in an isolated perfused heart preparation. Similar trend was observed in the relative accumulation of lysophospholipid and non-esterified fatty acid levels during ischaemia, i.e. both were significantly attenuated by amiodarone treatment. However, in contrast to the fatty acid data, the net changes in lysophospholipids per gram tissue wet weight were similar in treated and untreated animals, suggesting that the protective effects of amiodarone may have involved other enzymes including phospholipase C and D. Also, during the entire time course studied, all the phospholipid classes appeared to be affected to more or less a similar degree, indicating that the effects of the drug may have manifested in other subcellular compartments besides lysosommes. However, at all time periods studied, the net release of eicosatetraenoic and docosahexaenoic acid (fatty acids occupying primarily sn-2 position of phospholipids) was different, release of the former fatty acid being inhibited more than the latter, suggesting specific interaction of amiodarone with the molecular species of phospholipid. The data suggest that amiodarone attenuates ischaemia-induced membrane lipid abnormalities in part through modulation of phospholipid metabolism, and that this effect may be one of the key determinants which contribute to its antiarrhythmic properties during acute ischaemia.</abstract><note type="content">Section title: Original article</note><subject><genre>Keywords</genre><topic>Amiodarone therapy</topic><topic>in vitro total ischaemia</topic><topic>Isolated perfused heart</topic><topic>Time-course of phospholipid hydrolysis</topic><topic>Lysophospholipid accumulation</topic><topic>Fatty acid release</topic></subject><relatedItem type="host"><titleInfo><title>Journal of Molecular and Cellular Cardiology</title></titleInfo><titleInfo type="abbreviated"><title>YJMCC</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1992</dateIssued></originInfo><identifier type="ISSN">0022-2828</identifier><identifier type="PII">S0022-2828(00)X0212-X</identifier><part><date>1992</date><detail type="volume"><number>24</number><caption>vol.</caption></detail><detail type="issue"><number>5</number><caption>no.</caption></detail><extent unit="issue-pages"><start>451</start><end>567</end></extent><extent unit="pages"><start>507</start><end>521</end></extent></part></relatedItem><identifier type="istex">0F1479CA463F91A1600360B7A7C0731E37661866</identifier><identifier type="ark">ark:/67375/6H6-CC8GJMVS-4</identifier><identifier type="DOI">10.1016/0022-2828(92)91840-2</identifier><identifier type="PII">0022-2828(92)91840-2</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-CC8GJMVS-4/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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