TY - JOUR
T1 - ST segment elevation by current-to-load mismatch: an experimental and computational study
AU - Hoogendijk, Mark G.
AU - Potse, Mark
AU - Vinet, Alain
AU - de Bakker, Jacques M. T.
AU - Coronel, Ruben
PY - 2011
Y1 - 2011
N2 - 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 width. Total conduction block occurred in three of four preparations with isthmuses of 0.9 mm versus one of seven with isthmuses >= 1.1 mm (P <.05). Excitation failure resulted in ST segment elevation on the pseudo-ECG. In computer simulations, subepicardial structural discontinuities caused local activation delay and made the success of conduction sensitive to I-Na, I-to, and I-CaL. Reduction of I-to and increase of I-CaL resulted in a higher excitatory current, overcame subepicardial excitation failure, and reduced the ST segment elevation. CONCLUSIONS Excitation failure by current-to-load mismatch causes ST segment elevation and, like ST segment elevation in Brugada patients, is modulated by I-to and I-CaL
AB - 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 width. Total conduction block occurred in three of four preparations with isthmuses of 0.9 mm versus one of seven with isthmuses >= 1.1 mm (P <.05). Excitation failure resulted in ST segment elevation on the pseudo-ECG. In computer simulations, subepicardial structural discontinuities caused local activation delay and made the success of conduction sensitive to I-Na, I-to, and I-CaL. Reduction of I-to and increase of I-CaL resulted in a higher excitatory current, overcame subepicardial excitation failure, and reduced the ST segment elevation. CONCLUSIONS Excitation failure by current-to-load mismatch causes ST segment elevation and, like ST segment elevation in Brugada patients, is modulated by I-to and I-CaL
U2 - https://doi.org/10.1016/j.hrthm.2010.09.066
DO - https://doi.org/10.1016/j.hrthm.2010.09.066
M3 - Article
C2 - 20870038
SN - 1547-5271
VL - 8
SP - 111
EP - 118
JO - Heart Rhythm
JF - Heart Rhythm
IS - 1
ER -