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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Bibliographic Details
Published in:Canadian journal of physiology and pharmacology 2021-01, Vol.99 (1), p.102-109
Main Authors: 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
Format: Article
Language:English
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
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Summary: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.
ISSN:0008-4212
1205-7541
DOI:10.1139/cjpp-2020-0386