Figure 1.
Effect of diclofenac on action potentials in canine right ventricular muscle preparations and in Purkinje fibers.
Representative superimposed records (top) demonstrating the effect of 20 µM diclofenac on action potential configuration at 1 s stimulation cycle length (A, right ventricular muscle; B, Purkinje fiber). Cycle length dependent changes in action potential duration (APD90) measured under control conditions and in the presence of 20 µM diclofenac (bottom) in canine right ventricular muscle preparations (A) and in Purkinje fibers (B). Data are expressed as mean ± SEM, n = number of measurements/number of animals.
Figure 2.
Effect of diclofenac on action potential repolarization in canine right ventricular preparations with impaired repolarization reserve.
(A) Representative superimposed action potentials recorded from canine right ventricular muscle preparation at cycle length of 1 s. In these experiments 30 µM BaCl2 was applied to attenuate the repolarization reserve prior to 20 µM diclofenac superfusion. (B) Cycle length dependent changes in APD90 measured under the specified experimental conditions in canine right ventricular muscle preparation. Data are expressed as mean ± SEM, n = number of measurements/number of animals.
Figure 3.
Effect of diclofenac on repolarization and TdP incidence in anesthetized rabbits.
(A) Frequency corrected QT intervals (QTc) and (B) incidence of Torsades de Pointes ventricular tachycardia (TdP) in anaesthetized rabbits before and following dofetilide (25 µg/kg), dofetilide+diclofenac (3 mg/kg) and diclofenac, diclofenac+dofetilide administration. *p<0.05 vs. control, +p<0.05 vs. diclofenac, §p<0.05 vs. dofetilide, n = 15 and 13 animals/group, respectively. (C) Representative ECG recordings illustrate TdP development only after dofetilide or diclofenac+dofetilide combination, but not following diclofenac administration. #p<0.05 vs. baseline, n = 13 and 15 animals/group, respectively.
Figure 4.
Lack of effect of diclofenac on the transient outward potassium (Ito) and on the inward rectifier potassium (IK1) currents in canine ventricular myocytes.
A, top: Representative Ito current traces under control conditions and after application of 50 µM diclofenac. A, bottom: Current – voltage relationships of Ito under control conditions and in the presence of 50 µM diclofenac. Panel B shows steady-state current – voltage relationships of IK1 before and after application of 50 µM diclofenac. Insets depict the voltage protocol applied during measurements. Data are expressed as mean ± SEM, n = number of measurements/number of animals.
Figure 5.
Effect of diclofenac on the rapid (IKr) and slow (IKs) component of the delayed rectifier potassium currents in canine ventricular myocytes.
Top panels show representative current traces (A, IKr; B, IKs), bottom panels represent current – voltage relationships under control conditions and in the presence of 30 µM diclofenac. Insets indicate the voltage protocol applied during measurements. Data are expressed as mean ± SEM, n = number of measurements/number of animals.
Figure 6.
Effect of diclofenac on the L-type calcium current in canine ventricular myocytes.
Top panel shows representative current traces, bottom panel represents current – voltage relationships under control conditions and in the presence of 30 µM diclofenac. Inset indicates the voltage protocol applied during measurements. Data are expressed as mean ± SEM, n = number of measurements/number of animals.