ST segment elevation by current-to-load mismatch: an experimental and computational study

BACKGROUND Recently, we demonstrated that ajmaline caused ST segment elevation in the heart of an SCN5A mutation carrier by excitation failure in structurally discontinuous myocardium. In patients with Brugada syndrome, ST segment elevation is modulated by cardiac sodium (I(Na)), transient outward (I(to)), and L-type calcium currents (I(CaL)). OBJECTIVE To establish experimentally whether excitation failure by current-to-load mismatch causes ST segment elevation and is modulated by I(to) and I(CaL). METHODS In porcine epicardial shavings, isthmuses of 0.9, 1.1, or 1.3 mm in width were created parallel to the fiber orientation. Local activation was recorded electrically or optically (di-4ANEPPS) simultaneously with a pseudo-electrocardiogram (ECG) before and after ajmaline application. Intra-and extracellular potentials and ECGs were simulated in a computer model of the heart and thorax before and after introduction of right ventricular structural discontinuities and during varying levels of I(Na), I(to), and I(CaL). RESULTS In epicardial shavings, conduction blocked after ajmaline in a frequency-dependent manner in all preparations with isthmuses = 1.1 mm (P