Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by
alpha-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar
electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the
intravenous administration of
naftopidil (alpha(1)-
adrenergic blocker: 0.2 mg/kg, n = 6),
yohimbine (alpha(2)-
adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (
hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial
tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted
a 19% decrease of the sites still able to induce atrial
tachyarrhythmias.
Hexamethonium inactivated 78% of the previously active sites. Combined alpha-
adrenoceptor blockade inactivated 72% of the previously active sites.
Bradycardia responses induced by mediastinal nerve stimulation were blunted by
hexamethonium, but not by alpha(1,2)-adrenergic blockade.
Naftopidil or
yohimbine alone eliminated atrial
arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal alpha-
adrenoceptors. In contrast to the global suppression exerted by
hexamethonium, we conclude that alpha-
adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in
arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system.