In Vitro Effects of Acute Amiodarone and Dronedarone on Epicardial, Endocardial, and M Cells of the Canine Ventricle

Moro, Sandra; Ferreiro, Marcela; Celestino, Daniela; Medei, Emiliano; Elizari, Marcelo V.; Sicouri, Serge

doi:10.1177/1074248407306906

Cited by 16 publications

(9 citation statements)

References 36 publications

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“…Acute dronedarone has been reported to produce variable but a generally small or no effect to alter APD (12–16). In rabbit superfused cardiac preparations, acute dronedarone abbreviated APD in both atria and ventricles (14,15).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of the Combination of Ranolazine and Dronedarone to Suppress Atrial Fibrillation

Burashnikov

Sicouri

Diego

et al. 2010

Journal of the American College of Cardiology

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118

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Objectives The aim of this study was to evaluate the effectiveness of a combination of dronedarone and ranolazine in suppression of atrial fibrillation (AF). Background Safe and effective pharmacological management of AF remains one of the greatest unmet medical needs. Methods The electrophysiological effects of dronedarone (10 μmol/l) and a relatively low concentration of ranolazine (5 μmol/l) separately and in combination were evaluated in canine isolated coronary-perfused right and left atrial and left ventricular preparations as well as in pulmonary vein preparations. Results Ranolazine caused moderate atrial-selective prolongation of action potential duration and atrial-selective depression of sodium channel–mediated parameters, including maximal rate of rise of the action potential upstroke, leading to the development of atrial-specific post-repolarization refractoriness. Dronedarone caused little or no change in electrophysiological parameters in both atrial and ventricular preparations. The combination of drone-darone and ranolazine caused little change in action potential duration in either chamber but induced potent use-dependent atrial-selective depression of the sodium channel–mediated parameters (maximal rate of rise of the action potential upstroke, diastolic threshold of excitation, and the shortest cycle length permitting a 1:1 response) and considerable post-repolarization refractoriness. Separately, dronedarone or a low concentration of ranolazine prevented the induction of AF in 17% and 29% of preparations, respectively. In combination, the 2 drugs suppressed AF and triggered activity and prevented the induction of AF in 9 of 10 preparations (90%). Conclusions Low concentrations of ranolazine and dronedarone produce relatively weak electrophysiological effects and weak suppression of AF when used separately but when combined exert potent synergistic effects, resulting in atrial-selective depression of sodium channel–dependent parameters and effective suppression of AF. (J Am Coll Cardiol 2010;56:1216–24)

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Section: Discussionmentioning

confidence: 99%

Synergistic Effect of the Combination of Ranolazine and Dronedarone to Suppress Atrial Fibrillation

Burashnikov

Sicouri

Diego

et al. 2010

Journal of the American College of Cardiology

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118

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“…25 Similarly, dronedarone reduced transmural dispersion of repolarization and abolished d-sotalol-induced early afterdepolarizations in canine left ventricular tissue slices. 38 Thus dronedarone has multichannel blocking properties comparable to those of amiodarone. It is a more potent blocker of peak sodium current and I K-Ach currents and has stronger in vitro antiadrenergic effects compared with amiodarone.…”

Section: Electrophysiological Properties Of Dronedarone In Vitro Expementioning

confidence: 99%

Dronedarone

2009

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Abstract-Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. It has been studied for maintenance of sinus rhythm and control of ventricular response during episodes of atrial fibrillation. Dronedarone reduces mortality and morbidity in patients with high-risk atrial fibrillation, but may be unsafe in those with severe heart failure. This article will review evidence of safety and effectiveness of dronedarone in patients with atrial fibrillation. Key Words: amiodarone Ⅲ arrhythmia Ⅲ atrial fibrillations Ⅲ dronedarone A trial fibrillation (AF) is the most common arrhythmia in clinical practice and a usual cause for hospitalization and consultation. 1,2 It is an epidemic. It is projected that by 2050, more than 15 million people will contract AF in the United States alone. 2,3 Nearly 1 in every 10 persons aged 80 years and older has AF, 1,4,5 predisposing them to stroke, heart failure, and death. 6,7 A recent report from Centers for Medicare and Medicaid Services suggested that AF accounted for 1 765 304 hospitalizations in 1999. 8 The cost of medical care for patients with AF is almost 5 times higher than the care of patients without AF. 9,10 Despite improvements in primary and secondary prevention of ischemic heart disease and hypertension, the US age-adjusted death rate due to AF increased from 27.6 in 1980 to 69.8 per 100 000 in 1998. 2,11 Current therapy for AF is multidimensional and complicated. 12 There is some consensus on the benefits of anticoagulation in patients with AF, but debate continues about the relative value of rate versus rhythm control. Recent clinical trials have failed to demonstrate superiority of sinus rhythm maintenance, 13-18 but antiarrhythmic therapy is important for patients with severe symptoms. Conventional antiarrhythmic drugs have limited efficacy and safety. In fact, data suggest that the benefit of restoring and maintaining sinus rhythm in AF may be offset by significant cardiac and extracardiac side effects of currently used drugs. 19 -21 Improvement in the current approach to AF is clearly necessary. This review focuses on dronedarone, a new antiarrhythmic drug for AF suppression (Figure 1). Electrophysiological Properties of Dronedarone In Vitro ExperimentsIn vitro electrophysiological properties of dronedarone and its comparison with amiodarone are summarized in Table...

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“…In canine cardiac papillary muscle preparation, acute effect of dronedarone (0.1–10 µ mol/ l ) shortened action potential duration (APD), whereas the sustained effect did not alter APD [37]. In canine left ventricular Purkinje fibers and tissue slices, dronedarone lowered the incidence of triggered activities [22, 37]. Only a few studies have reported the dronedarone effects on QT and QTc intervals in healthy and complete AV block dogs [26, 37, 38].…”

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confidence: 99%

Acute effects of intravenous dronedarone on electrocardiograms, hemodynamics and cardiac functions in anesthetized dogs

Saengklub

Limprasutr

Sawangkoon

et al. 2016

The Journal of Veterinary Medical Science

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ABSTRACT. Dronedarone is a class III antiarrhythmic that has been used for management of atrial fibrillation in humans, but limited information was found in dogs. The objective of this study was to determine the acute effects of escalating concentrations of dronedarone on electrocardiograms (ECG), hemodynamics and cardiac mechanics in healthy dogs. A total of 7 beagle dogs were anesthetized with isoflurane and instrumented to obtain lead II ECG, pressures at ascending aorta, right atrium, pulmonary artery and left ventricle, and left ventricular pressure-volume relationship. Five dogs were given vehicle and followed by escalating doses of dronedarone (0.5, 1.0 and 2.5 mg/kg, 15 min for each dose), and two dogs were used as a vehicle-treated control. All parameters were measured at 15 min after the end of each dose. The results showed that all parameters in vehicle-treated dogs were unaltered. Dronedarone at 2.5 mg/kg significantly lengthened PQ interval (P<0.01), reduced cardiac output (P<0.01) and increased systemic vascular resistance (P<0.01). Dronedarone produced negative inotropy assessed by significantly lowered end-systolic pressure-volume relationship, preload recruitable stroke work, contractility index and dP/dt max . It also impaired diastolic function by significantly increased end-diastolic pressure-volume relationship, tau and dP/dt min . These results suggested that acute effects of dronedarone produced negative dromotropy, inotropy and lusitropy in anesthetized dogs. Care should be taken when given dronedarone to dogs, especially when the patients have impaired cardiac function.

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In Vitro Effects of Acute Amiodarone and Dronedarone on Epicardial, Endocardial, and M Cells of the Canine Ventricle

Cited by 16 publications

References 36 publications

Synergistic Effect of the Combination of Ranolazine and Dronedarone to Suppress Atrial Fibrillation

Synergistic Effect of the Combination of Ranolazine and Dronedarone to Suppress Atrial Fibrillation

Dronedarone

Acute effects of intravenous dronedarone on electrocardiograms, hemodynamics and cardiac functions in anesthetized dogs

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