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Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: possible implication to enhanced proarrhythmic risk
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential cha...
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Published in: | Canadian journal of physiology and pharmacology 2021-01, Vol.99 (1), p.102-109 |
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creator | Pászti, Bence Prorok, János Magyar, Tibor Árpádffy-Lovas, Tamás Györe, Balázs Topál, Leila Gazdag, Péter Szlovák, Jozefina Naveed, Muhammad Jost, Norbert Nagy, Norbert Varró, András Virág, László Koncz, István |
description | Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM;
= 6) and rabbit (100 µM;
= 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (
= 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence
, but decreased the amplitude of
and
potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed
and
currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients. |
doi_str_mv | 10.1139/cjpp-2020-0386 |
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= 6) and rabbit (100 µM;
= 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (
= 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence
, but decreased the amplitude of
and
potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed
and
currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.</description><identifier>ISSN: 0008-4212</identifier><identifier>EISSN: 1205-7541</identifier><identifier>DOI: 10.1139/cjpp-2020-0386</identifier><identifier>PMID: 32937079</identifier><language>eng</language><publisher>Canada: NRC Research Press</publisher><subject>Action potential ; Anti-inflammatory agents ; Antibiotics ; Arrhythmia ; Cardiac muscle ; Cardiovascular diseases ; Cardiovascular research ; Complications and side effects ; Depolarization ; Dosage and administration ; Electric properties ; Electrophysiology ; Frequency dependence ; Heart ; Ibuprofen ; Inflammation ; Levofloxacin ; Muscles ; Myocytes ; Nonsteroidal anti-inflammatory drugs ; Physiological aspects ; Potassium ; Potassium currents ; Purkinje fibers ; Risk factors ; Ventricle</subject><ispartof>Canadian journal of physiology and pharmacology, 2021-01, Vol.99 (1), p.102-109</ispartof><rights>COPYRIGHT 2021 NRC Research Press</rights><rights>2021 Published by NRC Research Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-93c29e1f52068160b823678d6b000f8d134007f19d5554f3e8c7a21b2f75d82a3</citedby><cites>FETCH-LOGICAL-c563t-93c29e1f52068160b823678d6b000f8d134007f19d5554f3e8c7a21b2f75d82a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32937079$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pászti, Bence</creatorcontrib><creatorcontrib>Prorok, János</creatorcontrib><creatorcontrib>Magyar, Tibor</creatorcontrib><creatorcontrib>Árpádffy-Lovas, Tamás</creatorcontrib><creatorcontrib>Györe, Balázs</creatorcontrib><creatorcontrib>Topál, Leila</creatorcontrib><creatorcontrib>Gazdag, Péter</creatorcontrib><creatorcontrib>Szlovák, Jozefina</creatorcontrib><creatorcontrib>Naveed, Muhammad</creatorcontrib><creatorcontrib>Jost, Norbert</creatorcontrib><creatorcontrib>Nagy, Norbert</creatorcontrib><creatorcontrib>Varró, András</creatorcontrib><creatorcontrib>Virág, László</creatorcontrib><creatorcontrib>Koncz, István</creatorcontrib><title>Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: possible implication to enhanced proarrhythmic risk</title><title>Canadian journal of physiology and pharmacology</title><addtitle>Can J Physiol Pharmacol</addtitle><description>Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM;
= 6) and rabbit (100 µM;
= 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (
= 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence
, but decreased the amplitude of
and
potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed
and
currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.</description><subject>Action potential</subject><subject>Anti-inflammatory agents</subject><subject>Antibiotics</subject><subject>Arrhythmia</subject><subject>Cardiac muscle</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular research</subject><subject>Complications and side effects</subject><subject>Depolarization</subject><subject>Dosage and administration</subject><subject>Electric properties</subject><subject>Electrophysiology</subject><subject>Frequency dependence</subject><subject>Heart</subject><subject>Ibuprofen</subject><subject>Inflammation</subject><subject>Levofloxacin</subject><subject>Muscles</subject><subject>Myocytes</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Physiological aspects</subject><subject>Potassium</subject><subject>Potassium currents</subject><subject>Purkinje fibers</subject><subject>Risk factors</subject><subject>Ventricle</subject><issn>0008-4212</issn><issn>1205-7541</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqVksmO1DAQhiMEYpqBK0dkwQUOGbxkceY2arGMNAKJ5Ww5Tjntxm1nbAfRj8Eb44hmadQX5IPl0ld_Lf6L4jHBF4Sw7qXaTlNJMcUlZry5U6wIxXXZ1hW5W6wwxrysKKFnxYMYt_nZcMbvF2eMdqzFbbcqvq9lGIxUCCyoFPy02UfjrR-NkhaB1jkakdfI9PMUvAaHjEODH5F0Awqy701CX8GlYNRsZUBTgEkGmYx38RJNPkbTW0BmN9ksuYRR8gjcRjoFQ8a9DGGzT5udUSiY-OVhcU9LG-HR4T4vPr9-9Wn9trx5_-Z6fXVTqrphqeyYoh0QXdM8FGlwzylrWj40fR5T84GwCuNWk26o67rSDLhqJSU91W09cCrZefH8p25u4XaGmMTORAXWSgd-joJWFeOc0BZn9Nk_6NbPweXuMsXzknMx-ocapQVhnPYpSLWIiqumxrRqCeOZKk9QIzgI0noH2uTwEf_0BK8mcyv-hi5OQPkMkNd6UvXFUUJmEnxLo5xjFNcfP_wH--6YPTSiQv75AFpMwexk2AuCxWJYsRhWLIYVi2FzwpPDaud-B8Nv_JdD2Q_hxuO7</recordid><startdate>202101</startdate><enddate>202101</enddate><creator>Pászti, Bence</creator><creator>Prorok, János</creator><creator>Magyar, Tibor</creator><creator>Árpádffy-Lovas, Tamás</creator><creator>Györe, Balázs</creator><creator>Topál, Leila</creator><creator>Gazdag, Péter</creator><creator>Szlovák, Jozefina</creator><creator>Naveed, Muhammad</creator><creator>Jost, Norbert</creator><creator>Nagy, Norbert</creator><creator>Varró, András</creator><creator>Virág, László</creator><creator>Koncz, István</creator><general>NRC Research Press</general><general>Canadian Science Publishing NRC Research Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>202101</creationdate><title>Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: possible implication to enhanced proarrhythmic risk</title><author>Pászti, Bence ; 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We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM;
= 6) and rabbit (100 µM;
= 7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (
= 7). In dog myocytes, ibuprofen (250 µM) did not significantly influence
, but decreased the amplitude of
and
potassium currents by 28.2% (60 mV) and 15.2% (20 mV), respectively. Ibuprofen also depressed
and
currents by 19.9% and 16.4%, respectively. We conclude that ibuprofen seems to be free from effects on action potential parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.</abstract><cop>Canada</cop><pub>NRC Research Press</pub><pmid>32937079</pmid><doi>10.1139/cjpp-2020-0386</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Action potential Anti-inflammatory agents Antibiotics Arrhythmia Cardiac muscle Cardiovascular diseases Cardiovascular research Complications and side effects Depolarization Dosage and administration Electric properties Electrophysiology Frequency dependence Heart Ibuprofen Inflammation Levofloxacin Muscles Myocytes Nonsteroidal anti-inflammatory drugs Physiological aspects Potassium Potassium currents Purkinje fibers Risk factors Ventricle |
title | Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: possible implication to enhanced proarrhythmic risk |
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