Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
MTA-SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary.
Can J Physiol Pharmacol. 2021 Jan;99(1):102-109. doi: 10.1139/cjpp-2020-0386. Epub 2020 Sep 16.
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.
布洛芬是一种广泛使用的非甾体抗炎药，最近与心血管风险增加有关，但在分离的心脏制剂中尚未对其电生理效应进行适当研究。我们使用传统的微电极技术和膜片钳全细胞技术在心脏制剂和酶分离的心室肌细胞上研究了布洛芬对动作电位特征和几种跨膜离子电流的影响。在狗（200 µM；n = 6）和兔（100 µM；n = 7）乳头肌中，布洛芬适度但显著延长了 1 Hz 刺激频率下的复极化。在狗浦肯野纤维中，复极化缩短，最大去极化速率呈频率依赖性降低。左氧氟沙星（40 µM）单独使用不会改变复极化，但在兔制剂中增强了布洛芬引起的复极化延长（n = 7）。在狗心肌细胞中，布洛芬（250 µM）对 没有显著影响，但使 钾电流的幅度分别降低了 28.2%（60 mV）和 15.2%（20 mV）。布洛芬还使 和 电流分别降低了 19.9%和 16.4%。我们得出结论，布洛芬在较低浓度下似乎对动作电位参数没有影响。然而，在较高浓度下，它可能会改变复极化储备，导致观察到的患者心律失常风险增加。
