Key result
Quinidine at a clinical therapeutic concentration of 10 µM significantly depressed the transmural electrical heterogeneity of the transient outward potassium current in the right ventricular outflow tract by 66.5% at steady state.
Quinidine at clinical therapeutic concentrations effectively depresses the transmural electrical heterogeneity of transient outward potassium current in the RVOT free wall, providing mechanistic insight into its efficacy in Brugada syndrome.
Quinidine merits further Brugada syndrome study; leaves open clinical translation from this animal model.
BACKGROUND#ENTITYSTARTX02014;: Electrical heterogeneity of the right ventricular outflow tract (RVOT) is regarded as one of the main electrophysiological substrates for Brugada syndrome. Recently quinidine has shown efficacy in patients with Brugada syndrome due to its ability to inhibit potassium current especially 4-aminopyridine-sensitive, non-Ca(2+) -dependent transient outward potassium current (Ito). However, much less is known on how extent quinidine in clinical therapeutic concentration range can inhibit this kind of electrical heterogeneity of RVOT Ito. METHODS AND RESULTS#ENTITYSTARTX02014;: Single RVOT free wall epicardial (Epi) cell, midmyocardial (M) cell and endocarcial (Endo) cells were used for whole-cell voltage clamping and Ito was recorded at 37°C, 0.2 Hz depolarization pulse. Evident Ito tranmural heterogeneity existed in RVOT free wall. Under the condition of baseline, of 10 μM quinidine perfusion 5 minutes (mins), and of 10 μM quinidine perfusion 7-10 mins, from 0 mV to 70 mV the whole transmural average Ito values of RVOT free wall were 10.2 pA/pF, 5.5 pA/pF and 3.5 pA/pF, respectively (between groups, P< 0.01). The inhibitory percentage of 10 μM quinidine at 5 mins and 7-10 mins steady-state level on the the whole Ito transmural heterogeneity of RVOT free wall were 46.3%±6% and 66.5%±11%, respectively. CONCLUSIONS#ENTITYSTARTX02014;: There exists a robust Ito transmural electrical heterogeneity in RVOT free wall and quinidine in clinical therapeutic concentration can depress this kind of heterogeneity effectively.
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Zhou et al. (2010) studied Brugada syndrome (experimental model) (n=15). Quinidine vs. Baseline (no quinidine) was evaluated on Whole transmural average Ito values of RVOT free wall from 0 mV to 70 mV (66.5%±11% inhibition, p=<0.01). Quinidine at a clinical therapeutic concentration of 10 µM significantly depressed the transmural electrical heterogeneity of the transient outward potassium current in the right ventricular outflow tract by 66.5% at steady state.
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