Atrial fibrillation is the most common sustained arrhythmia affecting more than 2 million people annually in USA. Previous studies have shown that left ventricular hypertrophy (LVH) results in an increase in the late I
Na
that plays an important role in genesis of ventricular arrhythmias. We tested the hypothesis that LVH, which is associated with elevated pressure in the left atrium, could enhance the late I
Na
in left atrial (LA) myocytes, leading to increased trigger activities. Rabbit LVH, which exhibited a significantly greater left ventricle to body mass ratio, was induced using the renovascular hypertension model. Interestingly, early afterdepolarizations (EADs) at action potential phase 2 and 3 occurred in 6 of 10 LA myocytes isolated from 5 LVH rabbits at a pacing cycle length of 2000 ms, whereas EADs were elicited in none of 10 cells isolated from 5 control rabbits (
p
<0.01). Spontaneously activities (SA) were observed in 6 of 10 LA myocytes from five LVH rabbits at the pacing rate of 8000 ms. The density of the late I
Na
was significantly larger in LA myocytes of LVH rabbits than that recorded in control rabbits (0.59±0.02 pA/pF in LVH versus 0.42±0.05 pA/pF in control, n=6,
p
<0.01). Ranolazine, a late I
Na
blocker, exerted a concentration-dependent blocking effect on the late I
Na
in LA myocytes of the rabbits (IC
50
=15.7±0.6 μM) and abolished all of atrial EADs and SA of the LVH rabbits at 30 μM. Our results demonstrate that LVH results in a significant increase in the late I
Na
in the LA myocytes that may render these cells susceptible to genesis of EADs. The late I
Na
is a potentially useful ionic target by antiarrhythmic drugs for the treatment of atrial fibrillation in the setting of LVH.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Canine left ventricular hypertrophy predisposes to ventricular tachycardia induction by phase 2 early afterdepolarizations after administration of BAY K 8644
