159 research outputs found
Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve
Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-
inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle.
Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials
were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was
investigated in an anaesthetized rabbit proarrhythmia model.
Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac
(20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was
observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong
while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac
following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades
de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of
diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased
the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium
current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not
influenced.
Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and
does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen
repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve
Late sodium current and its contribution to action potential configuration in guinea pig ventricular myocytes.
The relation of localized myocardial warming to changes in cardiac surface electrograms in dogs.
Electrotonically mediated delayed conduction and reentry in relation to "slow responses" in mammalian ventricular conducting tissue.
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