Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts
Purpose Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na + current and has been shown to exert a protective effect against arrhythmias. The present study aims to determi...
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| Veröffentlicht in: | Cardiovascular drugs and therapy 2015-06, Vol.29 (3), p.231-241 |
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| creator | Chorro, Francisco J. del Canto, Irene Brines, Laia Such-Miquel, Luis Calvo, Conrado Soler, Carlos Parra, Germán Zarzoso, Manuel Trapero, Isabel Tormos, Álvaro Alberola, Antonio Such, Luis |
| description | Purpose
Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na
+
current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch.
Methods
The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (
n
= 9) or during perfusion of the late Na
+
current blocker ranolazine 5 μM (
n
= 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch.
Results
Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0
vs
40.4 %) (control: baseline =13.6 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz,
p
|
| doi_str_mv | 10.1007/s10557-015-6587-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1701339761</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1701339761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-2ac1415357ae655a0c60a46bb1fd3b24345488c7514d4a454069f60a3db0b1a73</originalsourceid><addsrcrecordid>eNp1kU9rGzEQxUVoSRwnHyCXIuilF7Ua_d09huA2AZeWtDkLrVaKN6xXrqQ9uJ--Mk5CKfQ0zOj33oh5CF0B_QiU6k8ZqJSaUJBEyUYTcYIWIDUnmgl4gxa0ZZRwRtUZOs_5iVZN2zan6Iwp4A0DukDp3k5xtL-HyePrUvw02-IzLhuPV6N3JcXdZp-HOMbHwdkRr0Ko04xjwF_30dnUD3X6oyRf3AYPE17b6dFPfUwhkO8-hTn7Ht_brhsKvvU2lXyB3gY7Zn_5XJfo4fPq580tWX_7cndzvSZOCFYIsw4ESC619UpKS52iVqiug9DzjgkupGgapyWIXtjaUNWGivC-ox1YzZfow9F3l-Kv2editkN2fhzt5OOcDWgKnLe63mKJ3v-DPsU5TfV3B4oKpRRrKwVHyqWYc_LB7NKwtWlvgJpDIOYYiKmBmEMgRlTNu2fnudv6_lXxkkAF2BHI9ameLv21-r-ufwBKUZX6</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1700466629</pqid></control><display><type>article</type><title>Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Chorro, Francisco J. ; del Canto, Irene ; Brines, Laia ; Such-Miquel, Luis ; Calvo, Conrado ; Soler, Carlos ; Parra, Germán ; Zarzoso, Manuel ; Trapero, Isabel ; Tormos, Álvaro ; Alberola, Antonio ; Such, Luis</creator><creatorcontrib>Chorro, Francisco J. ; del Canto, Irene ; Brines, Laia ; Such-Miquel, Luis ; Calvo, Conrado ; Soler, Carlos ; Parra, Germán ; Zarzoso, Manuel ; Trapero, Isabel ; Tormos, Álvaro ; Alberola, Antonio ; Such, Luis</creatorcontrib><description>Purpose
Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na
+
current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch.
Methods
The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (
n
= 9) or during perfusion of the late Na
+
current blocker ranolazine 5 μM (
n
= 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch.
Results
Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0
vs
40.4 %) (control: baseline =13.6 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz,
p
< 0.0001; ranolazine: baseline = 11.4 ± 1.8 Hz, stretch =14.0 ± 2.4 Hz,
p
< 0.05
vs
baseline,
p
< 0.001
vs
control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 ± 8 vs 38 ± 5 ms,
p
< 0.01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2 cm,
p
< 0.001) under ranolazine.
Conclusions
The late inward Na
+
current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch.</description><identifier>ISSN: 0920-3206</identifier><identifier>EISSN: 1573-7241</identifier><identifier>DOI: 10.1007/s10557-015-6587-4</identifier><identifier>PMID: 26138210</identifier><identifier>CODEN: CDTHET</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Biomechanical Phenomena - drug effects ; Cardiology ; Electrophysiological Phenomena - drug effects ; Heart - drug effects ; Heart - physiology ; Heart - physiopathology ; In Vitro Techniques ; Isolated Heart Preparation ; Medicine ; Medicine & Public Health ; Original Article ; Rabbits ; Ranolazine - pharmacology ; Ranolazine - therapeutic use ; Ventricular Fibrillation - drug therapy ; Ventricular Fibrillation - physiopathology</subject><ispartof>Cardiovascular drugs and therapy, 2015-06, Vol.29 (3), p.231-241</ispartof><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-2ac1415357ae655a0c60a46bb1fd3b24345488c7514d4a454069f60a3db0b1a73</citedby><cites>FETCH-LOGICAL-c442t-2ac1415357ae655a0c60a46bb1fd3b24345488c7514d4a454069f60a3db0b1a73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10557-015-6587-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10557-015-6587-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26138210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chorro, Francisco J.</creatorcontrib><creatorcontrib>del Canto, Irene</creatorcontrib><creatorcontrib>Brines, Laia</creatorcontrib><creatorcontrib>Such-Miquel, Luis</creatorcontrib><creatorcontrib>Calvo, Conrado</creatorcontrib><creatorcontrib>Soler, Carlos</creatorcontrib><creatorcontrib>Parra, Germán</creatorcontrib><creatorcontrib>Zarzoso, Manuel</creatorcontrib><creatorcontrib>Trapero, Isabel</creatorcontrib><creatorcontrib>Tormos, Álvaro</creatorcontrib><creatorcontrib>Alberola, Antonio</creatorcontrib><creatorcontrib>Such, Luis</creatorcontrib><title>Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts</title><title>Cardiovascular drugs and therapy</title><addtitle>Cardiovasc Drugs Ther</addtitle><addtitle>Cardiovasc Drugs Ther</addtitle><description>Purpose
Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na
+
current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch.
Methods
The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (
n
= 9) or during perfusion of the late Na
+
current blocker ranolazine 5 μM (
n
= 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch.
Results
Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0
vs
40.4 %) (control: baseline =13.6 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz,
p
< 0.0001; ranolazine: baseline = 11.4 ± 1.8 Hz, stretch =14.0 ± 2.4 Hz,
p
< 0.05
vs
baseline,
p
< 0.001
vs
control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 ± 8 vs 38 ± 5 ms,
p
< 0.01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2 cm,
p
< 0.001) under ranolazine.
Conclusions
The late inward Na
+
current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch.</description><subject>Animals</subject><subject>Biomechanical Phenomena - drug effects</subject><subject>Cardiology</subject><subject>Electrophysiological Phenomena - drug effects</subject><subject>Heart - drug effects</subject><subject>Heart - physiology</subject><subject>Heart - physiopathology</subject><subject>In Vitro Techniques</subject><subject>Isolated Heart Preparation</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Original Article</subject><subject>Rabbits</subject><subject>Ranolazine - pharmacology</subject><subject>Ranolazine - therapeutic use</subject><subject>Ventricular Fibrillation - drug therapy</subject><subject>Ventricular Fibrillation - physiopathology</subject><issn>0920-3206</issn><issn>1573-7241</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kU9rGzEQxUVoSRwnHyCXIuilF7Ua_d09huA2AZeWtDkLrVaKN6xXrqQ9uJ--Mk5CKfQ0zOj33oh5CF0B_QiU6k8ZqJSaUJBEyUYTcYIWIDUnmgl4gxa0ZZRwRtUZOs_5iVZN2zan6Iwp4A0DukDp3k5xtL-HyePrUvw02-IzLhuPV6N3JcXdZp-HOMbHwdkRr0Ko04xjwF_30dnUD3X6oyRf3AYPE17b6dFPfUwhkO8-hTn7Ht_brhsKvvU2lXyB3gY7Zn_5XJfo4fPq580tWX_7cndzvSZOCFYIsw4ESC619UpKS52iVqiug9DzjgkupGgapyWIXtjaUNWGivC-ox1YzZfow9F3l-Kv2editkN2fhzt5OOcDWgKnLe63mKJ3v-DPsU5TfV3B4oKpRRrKwVHyqWYc_LB7NKwtWlvgJpDIOYYiKmBmEMgRlTNu2fnudv6_lXxkkAF2BHI9ameLv21-r-ufwBKUZX6</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Chorro, Francisco J.</creator><creator>del Canto, Irene</creator><creator>Brines, Laia</creator><creator>Such-Miquel, Luis</creator><creator>Calvo, Conrado</creator><creator>Soler, Carlos</creator><creator>Parra, Germán</creator><creator>Zarzoso, Manuel</creator><creator>Trapero, Isabel</creator><creator>Tormos, Álvaro</creator><creator>Alberola, Antonio</creator><creator>Such, Luis</creator><general>Springer US</general><general>Springer Nature B.V</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><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150601</creationdate><title>Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts</title><author>Chorro, Francisco J. ; del Canto, Irene ; Brines, Laia ; Such-Miquel, Luis ; Calvo, Conrado ; Soler, Carlos ; Parra, Germán ; Zarzoso, Manuel ; Trapero, Isabel ; Tormos, Álvaro ; Alberola, Antonio ; Such, Luis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-2ac1415357ae655a0c60a46bb1fd3b24345488c7514d4a454069f60a3db0b1a73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Biomechanical Phenomena - drug effects</topic><topic>Cardiology</topic><topic>Electrophysiological Phenomena - drug effects</topic><topic>Heart - drug effects</topic><topic>Heart - physiology</topic><topic>Heart - physiopathology</topic><topic>In Vitro Techniques</topic><topic>Isolated Heart Preparation</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Original Article</topic><topic>Rabbits</topic><topic>Ranolazine - pharmacology</topic><topic>Ranolazine - therapeutic use</topic><topic>Ventricular Fibrillation - drug therapy</topic><topic>Ventricular Fibrillation - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chorro, Francisco J.</creatorcontrib><creatorcontrib>del Canto, Irene</creatorcontrib><creatorcontrib>Brines, Laia</creatorcontrib><creatorcontrib>Such-Miquel, Luis</creatorcontrib><creatorcontrib>Calvo, Conrado</creatorcontrib><creatorcontrib>Soler, Carlos</creatorcontrib><creatorcontrib>Parra, Germán</creatorcontrib><creatorcontrib>Zarzoso, Manuel</creatorcontrib><creatorcontrib>Trapero, Isabel</creatorcontrib><creatorcontrib>Tormos, Álvaro</creatorcontrib><creatorcontrib>Alberola, Antonio</creatorcontrib><creatorcontrib>Such, Luis</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular drugs and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chorro, Francisco J.</au><au>del Canto, Irene</au><au>Brines, Laia</au><au>Such-Miquel, Luis</au><au>Calvo, Conrado</au><au>Soler, Carlos</au><au>Parra, Germán</au><au>Zarzoso, Manuel</au><au>Trapero, Isabel</au><au>Tormos, Álvaro</au><au>Alberola, Antonio</au><au>Such, Luis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts</atitle><jtitle>Cardiovascular drugs and therapy</jtitle><stitle>Cardiovasc Drugs Ther</stitle><addtitle>Cardiovasc Drugs Ther</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>29</volume><issue>3</issue><spage>231</spage><epage>241</epage><pages>231-241</pages><issn>0920-3206</issn><eissn>1573-7241</eissn><coden>CDTHET</coden><abstract>Purpose
Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na
+
current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch.
Methods
The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (
n
= 9) or during perfusion of the late Na
+
current blocker ranolazine 5 μM (
n
= 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch.
Results
Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0
vs
40.4 %) (control: baseline =13.6 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz,
p
< 0.0001; ranolazine: baseline = 11.4 ± 1.8 Hz, stretch =14.0 ± 2.4 Hz,
p
< 0.05
vs
baseline,
p
< 0.001
vs
control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 ± 8 vs 38 ± 5 ms,
p
< 0.01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2 cm,
p
< 0.001) under ranolazine.
Conclusions
The late inward Na
+
current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26138210</pmid><doi>10.1007/s10557-015-6587-4</doi><tpages>11</tpages></addata></record> |
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| ispartof | Cardiovascular drugs and therapy, 2015-06, Vol.29 (3), p.231-241 |
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| language | eng |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Animals Biomechanical Phenomena - drug effects Cardiology Electrophysiological Phenomena - drug effects Heart - drug effects Heart - physiology Heart - physiopathology In Vitro Techniques Isolated Heart Preparation Medicine Medicine & Public Health Original Article Rabbits Ranolazine - pharmacology Ranolazine - therapeutic use Ventricular Fibrillation - drug therapy Ventricular Fibrillation - physiopathology |
| title | Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts |
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