During partial sodium channel blockade with flecainide, right ventricular conduction velocity decreased by 35.3% compared to 29.2% in the left ventricle, indicating increased RV conduction dependence.
The right ventricle has an increased conduction dependence on sodium channel availability due to lower Na(v)1.5 expression compared to the left ventricle, providing a mechanism for increased RV conduction sensitivity to flecainide.
Absolute Event Rate: 35.3% vs 29.2%
AIMS: The cardiac sodium current (I(Na)) is a major determinant of conduction. Mechanisms underlying regionally heterogeneous conduction slowing secondary to reduced I(Na) in diseases such as the Brugada syndrome and heart failure remain incompletely understood. Right precordial electrophysiological manifestations during flecainide challenge suggest a decreased right ventricular depolarization reserve. We hypothesized that heterogeneous cardiac sodium channel (Na(v)1.5) distribution between ventricles causes interventricular depolarization heterogeneities. METHODS AND RESULTS: Western blotting analysis revealed Na(v)1.5, and Kir2.1 protein expressions were 18.2 and 12.0% lower, respectively, in the guinea pig right ventricle (RV) compared with the left ventricle (LV). Conduction velocity (theta) heterogeneities were quantified by optical mapping during LV or RV pacing. Although RV transverse theta((thetaT)) was significantly greater than LV (thetaT) by 33.09 +/- 1.38% under control conditions, there were no differences in longitudinal theta. During partial sodium channel blockade (flecainide, 0.5 microM), RV theta decreased by 35.3 +/- 1.3%, whereas LV theta decreased by 29.2 +/- 1.0%. These data demonstrate that the RV has an increased conduction dependence on sodium channel availability. Partial blockade of the inward rectifier potassium current (I(K1)) by BaCl(2) (10 microm) significantly increased theta in both ventricles under control conditions. However, BaCl(2) only increased conduction dependence on sodium channel availability in the LV. This suggests that the LV may have an increased depolarization reserve compared with the RV, but the larger I(K1) depresses control LV theta. CONCLUSION: Interventricular I(K1) heterogeneities may underlie conduction heterogeneities observed under control conditions. However, under conditions where I(Na) is functionally reduced in disease or during pharmacological sodium channel blockade, the heterogeneity in Na(v)1.5 expression may become a significant determinant of conduction heterogeneities.
Veeraraghavan et al. (Wed,) conducted a other in Brugada syndrome and heart failure (experimental model). Flecainide challenge vs. Left ventricle vs Right ventricle was evaluated on Decrease in conduction velocity (theta) during flecainide challenge. During partial sodium channel blockade with flecainide, right ventricular conduction velocity decreased by 35.3% compared to 29.2% in the left ventricle, indicating increased RV conduction dependence.