Studies have shown that alcohol consumption is an independent risk factor for paroxysmal atrial fibrillation. The mechanisms of this association are not clear, although alcohol intake could cause short-term biochemical reconstruction of ion channels (electrical remodeling).

To examine the underlying mechanisms of alcohol-induced atrial fibrillation, Dr. Yamashita and colleagues created a new rat model and used the rats to assess the anti-arrhythmic effects of the pure sodium channel blocker pilsicainide.

Investigators injected the rats intraperitoneally with ethanol (up to 4.4 g/kg) plus cyanamide (0-200 mg/kg). Then, they assayed gene expression of a series of K⁺ and HCN cardiac ion channels. They correlated results of the assays with electrophysiologic studies in isolated perfused hearts.

A single stimulus significantly increased the number of repetitive atrial responses from 4.8 to 23.2. Atrial refractory period shortened from 32 to 23 ms, and sinus cycle length decreased from 259 to 207 ms.

Introducing the pure sodium channel blocker pilsicainide effectively decreased the number of stimulus-induced repetitive atrial responses in a dose-dependent manner. The drug decreased the number of repetitive atrial responses despite no apparent change in wavelength index. Pilsicainide also prolonged intra-atrial conduction time and effective refractory period in a dose-dependent manner.

Although pilsicainide decreased repetitive atrial responses in most rats, the sodium channel blocker induced tachycardia that did not self-terminate in 2 out of 15 rats.

Dr. Yamashita and colleagues have successfully created a new rat model of alcohol-induced atrial fibrillation that includes upregulation of cardiac ion channels Kv1.5 and HCN4. The pure channel blocker, pilsicainide, induced a satisfactory suppression of arrhythmia in this model. This validates the current therapy for alcohol-induced paroxysmal arrhythmia and provides insight into the mechanisms behind this condition.