Experimental evidence for proarrhythmic effects of nonsteroidal anti-inflammatory drugs in a sensitive whole-heart model.
Action Potentials
/ drug effects
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ administration & dosage
Arrhythmias, Cardiac
/ chemically induced
Cardiac Electrophysiology
Diclofenac
/ administration & dosage
Dose-Response Relationship, Drug
Electrocardiography
Female
Ibuprofen
/ administration & dosage
Indomethacin
/ administration & dosage
Isolated Heart Preparation
Rabbits
Tachycardia, Ventricular
/ chemically induced
NSAID
QT-prolongation
anti-inflammatory drugs
antiarrhythmic drugs
cardiac arrhythmias
nonsteroidal
rheumatic disorders
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
revised:
21
09
2021
received:
23
08
2021
accepted:
05
10
2021
pubmed:
12
10
2021
medline:
17
3
2022
entrez:
11
10
2021
Statut:
ppublish
Résumé
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. 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 (APD 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.
Sections du résumé
BACKGROUND
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 AND RESULTS
RESULTS
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 (APD
CONCLUSION
CONCLUSIONS
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.
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Diclofenac
144O8QL0L1
Ibuprofen
WK2XYI10QM
Indomethacin
XXE1CET956
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103-109Subventions
Organisme : Deutsche Stiftung für Herzforschung
Organisme : Hans-and-Gertie Fischer Foundation
Informations de copyright
© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Références
Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995;274(23):1870-1873.
Kawai S. Cyclooxygenase selectivity and the risk of gastro-intestinal complications of various non-steroidal anti-inflammatory drugs: a clinical consideration. Inflamm Res. 1998;47(Suppl 2):S102-S106.
Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:7086.
Pratt CM, Hertz RP, Ellis BE, Crowell SP, Louv W, Moye L. Risk of developing life-threatening ventricular arrhythmia associated with tefenadine in comparison with over-the-counter antihistamines, ibuprofen and clemastine. Am J Cardiol. 1994;73(5):346-352.
Fagbemi SO. The effect of aspirin, indomethacin and sodium meclofenamate on coronary artery ligation arrhythmias in anaesthetized rats. Eur J Pharmacol. 1984;97(3-4):283-287.
Yang ZF, Wang HW, Zheng YQ, Zhang Y, Liu YM, Li CZ. Possible arrhythmiogenic mechanism produced by ibuprofen. Acta Pharmacol Sin. 2008;29(4):421-429.
Bernier M, Alyea EP, Hearse DJ. Reperfusion-induced arrhythmias are not prevented by ibuprofen in isolated rat heart. Free Radic Biol Med. 1990;8(6):515-521.
Tripathi RM, Kaushal R. Effect of some non-steroidal anti-inflammatory drugs on ouabain-induced arrhythmias in guinea-pigs. Br J Pharmacol. 1988;93(4):747-750.
Kristof A, Husti Z, Koncz I, et al. Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve. PLoS One. 2012;7(12):e53255.
Eckardt L, Haverkamp W, Mertens H, et al. Drug-related torsades de pointes in the isolated rabbit heart: comparison of clofilium, d,l-sotalol, and erythromycin. J Cardiovasc Pharmacol. 1998;32(3):425-434.
Tveden-Nyborg P, Bergmann TK, Jessen N, Simonsen U, Lykkesfeldt J. BCPT policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol. 2021;128(1):4-8.
Legg T, Paluch E, Jayawardena S. Single- and multiple-dose pharmacokinetics of immediate-release/extended-release ibuprofen tablets. Clin Pharmacol Drug Dev. 2017;6(1):36-43.
Lucas S. The pharmacology of indomethacin. Headache. 2016;56(2):436-446.
Scheidel B, Blume H, Walter K, von Nieciecki A, Babej-Dolle RM. Biological availability of gastric juice-resistant coated diclofenac preparations. 1. Bioavailability study following a single administration of a multiple-unit formulation in comparison with a single-unit formulation. Arzneimittelforschung. 1993;43(11):1211-1215.
Edwards AG, Louch WE. Species-dependent mechanisms of cardiac arrhythmia: a cellular focus. Clin Med Insights Cardiol. 2017;11:1179546816686061.
Yarishkin OV, Hwang EM, Kim D, et al. Diclofenac, a non-steroidal anti-inflammatory drug, inhibits L-type Ca channels in neonatal rat ventricular cardiomyocytes. Korean J Physiol Pharmacol. 2009;13(6):437-442.
Lu HR, Vlaminckx E, Hermans AN, et al. Predicting drug-induced changes in QT interval and arrhythmias: QT-shortening drugs point to gaps in the ICHS7B Guidelines. Br J Pharmacol. 2008;154(7):1427-1438.
Shah RR, Bjerregaard P, Gussak I. Drug-induced QT interval shortening: an emerging component in integrated assessment of cardiac safety of drugs. J Electrocardiol. 2010;43(5):386-389.
Malik M. Drug-induced QT/QTc interval shortening: lessons from drug-induced QT/QTc prolongation. Drug Saf. 2016;39(7):647-659.
Shah RR, Hondeghem LM. Refining detection of drug-induced proarrhythmia: QT interval and TRIaD. Heart Rhythm. 2005;2(7):758-772.
Valentin JP, Hoffmann P, De Clerck F, Hammond TG, Hondeghem L. Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proarrhythmic potential of drugs. J Pharmacol Toxicol Methods. 2004;49(3):171-181.
Ellermann C, Wolfes J, Eckardt L, Frommeyer G. Role of the rabbit whole-heart model for electrophysiologic safety pharmacology of non-cardiovascular drugs. Europace. 2020.
Lepran I, Koltai M, Szekeres L. Effect of non-steroid anti-inflammatory drugs in experimental myocardial infarction in rats. Eur J Pharmacol. 1981;69(2):235-238.
Berti F, Rossoni G, Magni F, et al. Nonsteroidal antiinflammatory drugs aggravate acute myocardial ischemia in the perfused rabbit heart: a role for prostacyclin. J Cardiovasc Pharmacol. 1988;12(4):438-444.
Liu XK, Tosaki A, Engleman RM, Das DK. Salicylate reduces ventricular dysfunction and arrhythmias during reperfusion in isolated rat hearts. J Cardiovasc Pharmacol. 1992;19(2):209-215.
Romson JL, Bush LR, Haack DW, Lucchesi BR. The beneficial effects of oral ibuprofen on coronary artery thrombosis and myocardial ischemia in the conscious dog. J Pharmacol Exp Ther. 1980;215(1):271-278.
Tosaki A. ArrhythmoGenoPharmacoTherapy. Front Pharmacol. 2020;11:616.
Birincioglu M, Olmez E, Aksoy T, Acet A. The role of prostaglandin synthesis stimulation in the protective effect of captopril on ischaemia-reperfusion arrhythmias in rats in vivo. Pharmacol Res. 1997;36(4):299-304.
Chi Y, Ma Q, Ding XQ, Qin X, Wang C, Zhang J. Research on protective mechanism of ibuprofen in myocardial ischemia-reperfusion injury in rats through the PI3K/Akt/mTOR signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23(10):4465-4473.
Milberg P, Eckardt L, Bruns HJ, et al. Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes. J Pharmacol Exp Ther. 2002;303(1):218-225.
Sims C, Reisenweber S, Viswanathan PC, Choi BR, Walker WH, Salama G. Sex, age, and regional differences in L-type calcium current are important determinants of arrhythmia phenotype in rabbit hearts with drug-induced long QT type 2. Circ Res. 2008;102(9):e86-e100.