Mechanisms underlying the development of the electrocardiographic and arrhythmic manifestations of early repolarization syndrome.

ABSTRACT: Early repolarization pattern in the ECG has been associated with increased risk for ventricular tachycardia/fibrillation (VT/VF), particularly when manifest in inferior leads. This study examines the mechanisms underlying VT/VF in early repolarization syndrome (ERS). Transmembrane action potentials (APs) were simultaneously recorded from 2 epicardial sites and 1 endocardial site of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a pseudo-ECG. Transient outward current (Ito) was recorded from epicardial myocytes isolated from the inferior and lateral LV of the same heart. J wave area (pseudo-ECG), epicardial AP notch magnitude and index were larger in inferior vs. lateral wall preparations at baseline and after exposure to provocative agents (NS5806+verapamil+acetylcholine (ACh)). Ito density was greater in myocytes from inferior vs. lateral wall (18.4 ± 2.3pA/pF vs. 11.6 ± 2.0pA/pF; p<0.05). A combination of NS5806 (7 ?M) and verapamil (3 ?M) or pinacidil (4 ?M), used to pharmacologically model the genetic defects responsible for ERS, resulted in prominent J-point and ST-segment elevation. ACh (3 ?M), simulating increased vagal tone, precipitated phase-2-reentry-induced polymorphic VT/VF. Using identical protocols, inducibility of arrhythmias was 3-fold higher in inferior vs. lateral wedges. Quinidine (10 ?M) or isoproterenol (1 ?M) restored homogeneity and suppressed VT/VF. Our data support the hypothesis that 1) ERS is caused by a preferential accentuation of the AP notch in the LV epicardium; 2) this repolarization defect is accentuated by elevated vagal tone; 3) higher intrinsic levels of Ito account for the greater sensitivity of the inferior LV wall to development of VT/VF; and 4) quinidine and isoproterenol exert ameliorative effects by reversing the repolarization abnormality.

SUBMITTER: Koncz I 

PROVIDER: S-EPMC3943882 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature