Possible arrhythmiogenic mechanism produced by ibuprofen.
OBJECTIVE
The aim of the present study was to investigate the electrophysiological effect of ibuprofen on the cardiac action potentials (AP) and electrocardiograms (ECG), and to identify its arrhythmiogenic mechanism.


METHODS
The intracellular microelectrode recording technique was employed to record the fast- and slowresponse AP in guinea pig papillary muscles. The cardiac responses of ibuprofen were monitored by ECG, both in in vivo and in vitro studies.


RESULTS
The ECG recording revealed that ibuprofen could induce arrhythmias, both in vitro and in vivo. Fatal ventricular fibrillations are readily produced in in vitro experiments by ibuprofen. Our results show that ibuprofen could dose dependently shorten the duration of AP and the effective refractory period (ERP), and it could also decrease the maximum depolarization velocity of phase 0 (V(max)) in both the fast- and slow-response AP. The duration of the QRS complex wave (QRS duration) in ECG was prolonged. Although the heart rate was depressed by ibuprofen, the corrected QT interval duration (QTc) decreased.


CONCLUSIONS
Ibuprofen could inhibit cardiac Na+ and Ca2+ channels as it slows V(max) in both fast- and slowresponse AP. Furthermore, ibuprofen shortens the ERP and decreases the excitation propagation within the heart, which might provide a substrate for an arrhythmiogenic re-entry circuit. Taken together, we conclude that ibuprofen, when used improperly, may impose a potential hazard in inducing cardiac arrhythmias in patients with existing heart diseases.
Yang
Zhi-fang
ZF
Department of Physiology, Medical School, Shanghai Jiaotong University, Shanghai 200025, China.
Wang
Hong-wei
HW
Zheng
Yan-qian
YQ
Zhang
Yin
Y
Liu
Yuan-mou
YM
Li
Ci-zhen
CZ
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007052:Ibuprofen / Q000494:pharmacology*; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D007052:Ibuprofen