Experimental evidence for proarrhythmic effects of nonsteroidal anti-inflammatory drugs in a sensitive whole-heart model.
Basic Clin Pharmacol Toxicol
; 130(1): 103-109, 2022 Jan.
Article
de En
| MEDLINE
| ID: mdl-34634184
ABSTRACT
BACKGROUND:
Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS ANDRESULTS:
Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 µM), indomethacin (Group 2, n = 13; 10 and 20 µM) and diclofenac (Group 3, n = 13; 10 and 20 µM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations.CONCLUSION:
The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Troubles du rythme cardiaque
/
Anti-inflammatoires non stéroïdiens
/
Tachycardie ventriculaire
Type d'étude:
Diagnostic_studies
Limites:
Animals
Langue:
En
Journal:
Basic Clin Pharmacol Toxicol
Sujet du journal:
FARMACOLOGIA
/
TOXICOLOGIA
Année:
2022
Type de document:
Article
Pays d'affiliation:
Allemagne