Abstract 2669: Upregulation of Cardiac Sodium Channel Nav1.5 and Arrhythmias in Left Atrium in Left Ventricular Hypertrophy
Objectives: Left ventricular hypertrophy (LVH) is associated with left atrial enlargement and atrial arrhythmias. Previous studies have shown that LVH enhances the late sodium current (INa-L), leading to ventricular arrhythmias. The present study was to test the hypothesis that there is a parallel increase in INa-L in the left atrium (LA) that causes left atrial arrhythmias in LVH.
Methods & Results: The renovascular hypertension model was used to induce LVH and LA enlargement in rabbits. The ratio of LA weight/body weight was 0.21±0.01 g/kg in LVH group vs 0.13±0.01 g/kg in control (n=12, p<0.01). There was no significant difference in the ratio of right atrium (RA) weight/body weight between two groups. Expression of Nav1.5 in LA and RA was determined by reverse transcription-polymerase chain reaction. Compared with control rabbits, LVH resulted in a marked increase in Nav1.5 mRNA by 78±14% (n=6, p<0.01) and in INa-L (0.59±0.02 pA/pF vs 0.42±0.05 pA/pF, n=12, p<0.01) in LA but not in RA. Both early and delayed afterdepolarizations (EADs and DADs) occurred spontaneously in LA single myocytes in LVH (10 of 12 rabbits vs 0 of 12 in controls, p<0.01). However, there were no spontaneous arrhythmias in RA single myocytes in LVH. Ranolazine at 10 μM, an INa-L blocker, abolished all left atrial EADs and DADs. In the arterially perfused left atrial wedges, ATX-II, an INa-L enhancer, at 1 nM induced left atrial EADs and torsades, abolished by 10 μM Ranolazine, in 2 of 3 LVH rabbits but not in controls (0 of 4).
Conclusions: LVH is associated with upregulation of cardiac sodium channel Nav1.5 and an increase in INa-L in LA that may render LA myocytes susceptible to genesis of EADs, DADs and associated triggered activities.
This research has received full or partial funding support from the American Heart Association, Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).