August 1, 1987Circulation
Frequency-dependent effects of amiodarone on atrioventricular nodal function and slow-channel action potentials: evidence for calcium channel-blocking activity.
Why the study?
Does amiodarone and its metabolite produce frequency-dependent effects on AV nodal function and slow-channel action potentials in canine models?
Population
Open-chest, chloralose-anesthetized dogs and canine cardiac false tendons in vitro
Comparison
Intravenous amiodarone and desethylamiodarone vs Control conditions (absence of amiodarone)
Design
Preclinical
Authors
Discussion
Loading...
Member takes
Implication
Amiodarone introduces slower AV nodal recovery in canine models; leaves open translation to human rate-dependent antiarrhythmic effects.
Key Points
- To determine whether amiodarone and its active metabolite, desethylamiodarone, exert frequency-dependent effects on slow-channel tissues and atrioventricular nodal electrophysiology.
- Administered intravenous amiodarone and desethylamiodarone (10 or 25 mg/kg) to open-chest, chloralose-anesthetized dogs to measure atrioventricular conduction time and refractory period across variable pacing frequencies.
- Assessed the recovery kinetics of slow-channel action potential maximum upstroke velocity (Vmax) in isolated canine cardiac false tendons exposed to elevated potassium and isoproterenol in vitro.
- Amiodarone and desethylamiodarone markedly prolonged atrioventricular conduction time and refractory periods in vivo at higher stimulation rates, introducing a slow recovery component with a time constant of approximately 1 second compared to 70 milliseconds in controls.
- In vitro, amiodarone introduced a slower recovery phase of action potential Vmax, prolonging the recovery time constant from a baseline average of 74 milliseconds to 0.94 seconds.
Structured PICO
Does amiodarone and its metabolite produce frequency-dependent effects on AV nodal function and slow-channel action potentials in canine models?
P
Population
Open-chest, chloralose-anesthetized dogs and canine cardiac false tendons in vitro
I
Intervention
Intravenous amiodarone and desethylamiodarone (10 or 25 mg/kg)
C
Comparator
Control conditions (absence of amiodarone)
O
Outcome
Frequency dependence of effects on atrioventricular conduction time (AVCT), refractory period (AVERP), and slow-channel action potentials (Vmax)surrogate
Amiodarone produces heart rate-dependent changes in AV nodal function via use-dependent calcium-channel blockade, providing a mechanism for its selective depression of supraventricular tachyarrhythmias.
Cite This Study
Nattel et al. (1987) studied this question.